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1.	Söderlund, Zackarias (författare) Engineering the extracellular matrix to model diseases and orchestrate regeneration 2023 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The extracellular matrix is not only a scaffold to which cells attach, but it is also a matrix that communicates cell signals. Because of the interplay between cells and the extracellular matrix, changes in the extracellular matrix can steer cell fate. This opens up the opportunity to design and engineer the extracellular matrix to communicate changes to the cells. Thus, this thesis has focused on understanding which parameters and signals influence cells, but also on how to utilise this knowledge to engineer a completely defined extracellular matrix. The extracellular matrix can be modulated in several ways, such as cell attachment, degradation properties, porosity, stiffness as well as being easily functionalised with molecules of interest using click chemistry.Two of the papers in this thesis focus on the development of new tools for glycosaminoglycan research to get a better understanding of how this can be modulated to steer cell signalling. Glycosaminoglycans bind growth factors, which can then either act as a co-receptor to increase the potency of the growth factor or to protect the growth factors from being broken down or inactivated. The tools that we have developed open the possibility to better study the production of glycosaminoglycans from different types of cells and better understand what changes occur in glycosaminoglycan synthesis during disease.The second two papers in this thesis focus on understanding the extracellular matrix. Article number one focuses on the effect of different extracellular matrices and stretch on cells and their secretome. Article number two, which has been the focus of this thesis, utilises the new findings in the other articles about glycosaminoglycans and the extracellular matrix to create a synthetic and defined extracellular matrix. This extracellular matrix is modified with glycosaminoglycans to have a slow release of growth factors to instruct cells to differentiate both in vitro and in vivo.
2.	Palmquist, Anders, 1977, et al. (författare) Complex geometry and integrated macro-porosity: Clinical applications of electron beam melting to fabricate bespoke bone-anchored implants 2023 Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 156, s. 125-145 Forskningsöversikt (refereegranskat)abstract The last decade has witnessed rapid advancements in manufacturing technologies for biomedical implants. Additive manufacturing (or 3D printing) has broken down major barriers in the way of producing complex 3D geometries. Electron beam melting (EBM) is one such 3D printing process applicable to metals and alloys. EBM offers build rates up to two orders of magnitude greater than comparable laser-based technologies and a high vacuum environment to prevent accumulation of trace elements. These features make EBM particularly advantageous for materials susceptible to spontaneous oxidation and nitrogen pick-up when exposed to air (e.g., titanium and titanium-based alloys). For skeletal reconstruction(s), anatomical mimickry and integrated macro-porous architecture to facilitate bone ingrowth are undoubtedly the key features of EBM manufactured implants. Using finite element modelling of physiological loading conditions, the design of a prosthesis may be further personalised. This review looks at the many unique clinical applications of EBM in skeletal repair and the ground-breaking innovations in prosthetic rehabilitation. From a simple acetabular cup to the fifth toe, from the hand-wrist complex to the shoulder, and from vertebral replacement to cranio-maxillofacial reconstruction, EBM has experienced it all. While sternocostal reconstructions might be rare, the repair of long bones using EBM manufactured implants is becoming exceedingly frequent. Despite the various merits, several challenges remain yet untackled. Nevertheless, with the capability to produce osseointegrating implants of any conceivable shape/size, and permissive of bone ingrowth and functional loading, EBM can pave the way for numerous fascinating and novel applications in skeletal repair, regeneration, and rehabilitation. Statement of significance: Electron beam melting (EBM) offers unparalleled possibilities in producing contaminant-free, complex and intricate geometries from alloys of biomedical interest, including Ti6Al4V and CoCr. We review the diverse range of clinical applications of EBM in skeletal repair, both as mass produced off-the-shelf implants and personalised, patient-specific prostheses. From replacing large volumes of disease-affected bone to complex, multi-material reconstructions, almost every part of the human skeleton has been replaced with an EBM manufactured analog to achieve macroscopic anatomical-mimickry. However, various questions regarding long-term performance of patient-specific implants remain unaddressed. Directions for further development include designing personalised implants and prostheses based on simulated loading conditions and accounting for trabecular bone microstructure with respect to physiological factors such as patient's age and disease status.
3.	Dietrich, Franciele, et al. (författare) Effect of storage and preconditioning of healing rat Achilles tendon on structural and mechanical properties 2021 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Tendon tissue storage and preconditioning are often used in biomechanical experiments and whether this generates alterations in tissue properties is essential to know. The effect of storage and preconditioning on dense connective tissues, like tendons, is fairly understood. However, healing tendons are unlike and contain a loose connective tissue. Therefore, we investigated if storage of healing tendons in the fridge or freezer changed the mechanical properties compared to fresh tendons, using a pull-to-failure or a creep test. Tissue morphology and cell viability were also evaluated. Additionally, two preconditioning levels were tested. Rats underwent Achilles tendon transection and were euthanized 12 days postoperatively. Statistical analyzes were done with one-way ANOVA or Student’s t-test. Tissue force and stress were unaltered by storage and preconditioning compared to fresh samples, while high preconditioning increased the stiffness and modulus (p ≤ 0.007). Furthermore, both storage conditions did not modify the viscoelastic properties of the healing tendon, but altered transverse area, gap length, and water content. Cell viability was reduced after freezing. In conclusion, preconditioning on healing tissues can introduce mechanical data bias when having extensive tissue strength diversity. Storage can be used before biomechanical testing if structural properties are measured on the day of testing.
4.	Arndt, T, et al. (författare) Native-like Flow Properties of an Artificial Spider Silk Dope 2021 Ingår i: ACS biomaterials science & engineering. - : American Chemical Society (ACS). - 2373-9878. ; 7:2, s. 462-471 Tidskriftsartikel (refereegranskat)
5.	Hansson, Magnus L., et al. (författare) Artificial spider silk supports and guides neurite extension in vitro 2021 Ingår i: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 35:11 Tidskriftsartikel (refereegranskat)abstract Surgical intervention with the use of autografts is considered the gold standard to treat peripheral nerve injuries. However, a biomaterial that supports and guides nerve growth would be an attractive alternative to overcome problems with limited availability, morbidity at the site of harvest, and nerve mismatches related to autografts. Native spider silk is a promising material for construction of nerve guidance conduit (NGC), as it enables regeneration of cm-long nerve injuries in sheep, but regulatory requirements for medical devices demand synthetic materials. Here, we use a recombinant spider silk protein (NT2RepCT) and a functionalized variant carrying a peptide derived from vitronectin (VN-NT2RepCT) as substrates for nerve growth support and neurite extension, using a dorsal root ganglion cell line, ND7/23. Two-dimensional coatings were benchmarked against poly-d-lysine and recombinant laminins. Both spider silk coatings performed as the control substrates with regards to proliferation, survival, and neurite growth. Furthermore, NT2RepCT and VN-NT2RepCT spun into continuous fibers in a biomimetic spinning set-up support cell survival, neurite growth, and guidance to an even larger extent than native spider silk. Thus, artificial spider silk is a promising biomaterial for development of NGCs.
6.	Kumosa, Lucas, et al. (författare) Profound alterations in brain tissue linked to hypoxic episode after device implantation 2021 Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612. ; 278, s. 1-13 Tidskriftsartikel (refereegranskat)abstract To enable authentic interfacing with neuronal structures in the brain, preventing alterations of tissue during implantation of devices is critical. By transiently implanting oxygen microsensors into rat cortex cerebri for 2 h, substantial and long lasting (>1 h) hypoxia is routinely generated in surrounding tissues; this hypoxia is linked to implantation generated compressive forces. Preferential loss of larger neurons and reduced metabolic components in surviving neurons indicates decreased viability one week after such hypoxic, compressive implantations. By devising an implantation method that relaxes compressive forces; magnitude and duration of hypoxia generated following such an implantation are ameliorated and neurons appear similar to naïve tissues. In line with these observations, astrocyte proliferation was significantly more pronounced for more hypoxic, compressive implantations. Surprisingly, astrocyte processes were frequently found to traverse cellular boundaries into nearby neuronal nuclei, indicating injury induction of a previously not described astrocyte-neuron interaction. Found more frequently in less hypoxic, force-relaxed insertions and thus correlating to a more beneficial outcome, this finding may suggest a novel protective mechanism. In conclusion, substantial and long lasting insertion induced hypoxia around brain implants, a previously overlooked factor, is linked to significant adverse alterations in nervous tissue.
7.	Lin, CH, et al. (författare) In Vitro Study of Human Immune Responses to Hyaluronic Acid Hydrogels, Recombinant Spidroins and Human Neural Progenitor Cells of Relevance to Spinal Cord Injury Repair 2021 Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:7 Tidskriftsartikel (refereegranskat)abstract Scaffolds of recombinant spider silk protein (spidroin) and hyaluronic acid (HA) hydrogel hold promise in combination with cell therapy for spinal cord injury. However, little is known concerning the human immune response to these biomaterials and grafted human neural stem/progenitor cells (hNPCs). Here, we analyzed short- and long-term in vitro activation of immune cells in human peripheral blood mononuclear cells (hPBMCs) cultured with/without recombinant spidroins, HA hydrogels, and/or allogeneic hNPCs to assess potential host–donor interactions. Viability, proliferation and phenotype of hPBMCs were analyzed using NucleoCounter and flow cytometry. hPBMC viability was confirmed after exposure to the different biomaterials. Short-term (15 h) co-cultures of hPBMCs with spidroins, but not with HA hydrogel, resulted in a significant increase in the proportion of activated CD69+ CD4+ T cells, CD8+ T cells, B cells and NK cells, which likely was caused by residual endotoxins from the Escherichia coli expression system. The observed spidroin-induced hPBMC activation was not altered by hNPCs. It is resource-effective to evaluate human compatibility of novel biomaterials early in development of the production process to, when necessary, make alterations to minimize rejection risk. Here, we present a method to evaluate biomaterials and hPBMC compatibility in conjunction with allogeneic human cells.
8.	Lin, YY, et al. (författare) High-Throughput Peptide Derivatization toward Supramolecular Diversification in Microtiter Plates 2021 Ingår i: ACS nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 15:3, s. 4034-4044 Tidskriftsartikel (refereegranskat)
9.	Iseri, Emre (författare) Microfluidic Compartmentalization for Smart Materials, Medical Diagnostics and Cell Therapy 2022 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The organisation of fluids in small compartments is ubiquitous in nature, such as in the cellular composition of all life. This work explores several engineering avenues where microscale fluid compartmentalization can bring novel material properties or novel functionality in life sciences or medicine. Here, we introduce four unique compartmentalization methods: 1) 3D fluid self-organisation in microscaffolds (FLUID3EAMS), 2) 2D microcapillary arrays on a dipstick (Digital Dipstick), 3) a sliding microfluidic platform with cross-flow (Slip-X-Chip), and 4) compartmentalization by cutting of soft solid matter (Solidify & Cut). These methods were used in a wide range of applications. Within the area of smart materials, we applied FLUID3EAMS to synthesize materials with temperature-tuneable permeability and surface energy and to establish, in a well-controlled fashion, tissue-like materials in the form of 3D droplet interface bilayer networks. Solidify & Cut was used to form soft composites with a new type of magnetic behaviour, rotation-induced ferromagnetism, that allows easy reprogramming of the magnetization of magnetopolymers. Within the area of medical diagnostics, we applied Digital Dipstick to perform rapid digital bacterial culture in a dipstick format and obtained clinically relevant diagnostic results on samples from patients with a urinary tract infection. Furthermore, Slip-X-Chip enables particle concentration and washing as new functions in sliding microfluidic platforms, which significantly expands their potential application area. Finally, within the area of cell therapy, we explored the microencapsulation of high concentrations of therapeutic cells and presented a novel technique to fabricate core-shell microcapsules by exploiting the superior material properties of spider silk membranes.
10.	Micheletti, Chiara, et al. (författare) Ultrastructure and Nanoporosity of Human Bone Shown with Correlative On-Axis Electron and Spectroscopic Tomographies 2023 Ingår i: ACS Nano. - 1936-0851 .- 1936-086X. ; 17:24, s. 24710-24724 Tidskriftsartikel (refereegranskat)abstract Mineralized collagen fibrils are the building block units of bone at the nanoscale. While it is known that collagen fibrils are mineralized both inside their gap zones (intra-fibrillar mineralization) and on their outer surfaces (extra-fibrillar mineralization), a clear visualization of this architecture in three dimensions (3D), combining structural and compositional information over large volumes, but without compromising the resolution, remains challenging. In this study, we demonstrate the use of on-axis Z-contrast electron tomography (ET) with correlative energy-dispersive X-ray spectroscopy (EDX) tomography to examine rod-shaped samples with diameters up to 700 nm prepared from individual osteonal lamellae in the human femur. Our work mainly focuses on two aspects: (i) low-contrast nanosized circular spaces (“holes”) observed in sections of bone oriented perpendicular to the long axis of a long bone, and (ii) extra-fibrillar mineral, especially in terms of morphology and spatial relationship with respect to intra-fibrillar mineral and collagen fibrils. From our analyses, it emerges quite clearly that most “holes” are cross-sectional views of collagen fibrils. While this had been postulated before, our 3D reconstructions and reslicing along meaningful two-dimensional (2D) cross-sections provide a direct visual confirmation. Extra-fibrillar mineral appears to be composed of thin plates that are interconnected and span over several collagen fibrils, confirming that mineralization is cross-fibrillar, at least for the extra-fibrillar phase. EDX tomography shows mineral signatures (Ca and P) within the gap zones, but the signal appears weaker than that associated with the extra-fibrillar mineral, pointing toward the existence of dissimilarities between the two types of mineralization.
11.	Pless, Christian J., et al. (författare) Emerging strategies in 3D printed tissue models for in vitro biomedical research 2022 Ingår i: Bioprinting : From Multidisciplinary Design to Emerging Opportunities - From Multidisciplinary Design to Emerging Opportunities. - 9780323854306 - 9780323854313 ; , s. 207-246 Bokkapitel (refereegranskat)abstract 3D bioprinting has the potential to provide a unified framework for the manufacturing of tissue models for biomedical research, including drug discovery, disease modeling, and regenerative medicine. However, it remains challenging to 3D print replicas of human tissues that have accurate cell types, cellular densities, extracellular matrix compositions, and that can be assayed in a minimally invasive manner for chronic studies. Here, we review how recent breakthroughs in stem cell biology, tissue engineering, and materials science have led to novel 3D printing strategies that have the potential to solve these challenges.
12.	Albrektsson, Tomas, 1945, et al. (författare) An Imbalance of the Immune System Instead of a Disease Behind Marginal Bone Loss Around Oral Implants: Position Paper 2020 Ingår i: The International journal of oral & maxillofacial implants. - : Quintessence Publishing. - 1942-4434 .- 0882-2786. ; 35:3, s. 495-502 Tidskriftsartikel (refereegranskat)abstract PURPOSE: The purpose of this paper is to present evidence that supports the notion that the primary reason behind marginal bone loss and implant failure is immune-based and that bacterial actions in the great majority of problematic cases are of a secondary nature. MATERIALS AND METHODS: The paper is written as a narrative review. RESULTS: Evidence is presented that commercially pure titanium is not biologically inert, but instead activates the innate immune system of the body. For its function, the clinical implant is dependent on an immune/inflammatory defense against bacteria. Biologic models such as ligature studies have incorrectly assumed that the primary response causing marginal bone loss is due to bacterial action. In reality, bacterial actions are secondary to an imbalance of the innate immune system caused by the combination of titanium implants and ligatures, ie, nonself. This immunologic imbalance may lead to marginal bone resorption even in the absence of bacteria. CONCLUSION: Marginal bone loss and imminent oral implant failure cannot be properly analyzed without a clear understanding of immunologically caused tissue responses.
13.	Asa'ad, Farah, 1983, et al. (författare) Editorial: On the Inflammatory Cascade-From Bacteria Through the Epithelium to the Connective Tissue. 2022 Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 12 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
14.	Asa'ad, Farah, 1983, et al. (författare) Expression of MicroRNAs in Periodontal and Peri-Implant Diseases: A Systematic Review and Meta-Analysis. 2020 Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 21:11 Tidskriftsartikel (refereegranskat)abstract The purpose of this review was to evaluate the expression patterns of miRNAs in periodontal and peri-implant diseases, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker.Human and animal studies were included when evaluating expression of miRNAs between health and different forms/stages of diseases, in which microarray and/or real-time polymerase chain reaction (RT-PCR) was carried out to detect fold changes in gene expression. After full-text analysis, 43 articles were considered for a qualitative assessment, and 16 miRNAs were selected to perform meta-analysis.Based on human studies, results showed an overall upregulation of most of the evaluated miRNAs in periodontitis, with miRNA-142-3p and miRNA-146a being the most conclusive on both microarray and RT-PCR values and potentially serving as diagnostic biomarkers for disease activity. Conversely, miR-155 was the only miRNA revealing a statistically significant difference (SSD) (p < 0.05*) in experimental periodontitis models from RT-PCR values. Scarce scientific evidence is available from peri-implant diseases, however, most explored miRNAs in peri-implantitis were downregulated except for miR-145.Although our results revealed that a distinct differential expression of specific miRNAs can be noted between the state of health and disease, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases. MeSH Terms: periodontitis, peri-implantitis, epigenomics, microarray analysis, real-time polymerase chain reaction, microRNAs.Scientific background: Although most research identified different expression levels of miRNAs in periodontal and peri-implant diseases compared to their counterparts, their actual role in the pathogenesis of these conditions remains unclear. Therefore, we aimed to present a systematic review and meta-analysis on the expression patterns of miRNAs in periodontitis and peri-implantitis, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker.In periodontitis-related studies, miRNA-142-3p and miRNA-146a were the most conclusive on both microarray and RT-PCR values. Scarce scientific evidence is available from peri-implant diseases.Both miRNA-142-3p and miRNA-146a might serve as future diagnostic biomarkers for disease activity in periodontitis. Yet, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases.
15.	Asa'ad, Farah, 1983, et al. (författare) Genetic and Epigenetic Susceptibility of Peri-Implantitis 2022 Ingår i: Unfolding Peri-implantitis: Diagnosis, Prevention. - Spain : Quintessence. - 9788489873896 Bokkapitel (refereegranskat)abstract Peri-implantitis is a destructive disease of implant-supporting tissues induced by bacterial biofilm, which provokes an inflammatory host response, influenced by environmental, genetic, and epigenetic factors. Genetics is the science that deals with genes, heredity, and the variations that occur in our genes and DNA, while epigenetics refers to alterations in the gene expression that are not encoded in the DNA sequence, which result in the remodeling of the chromatin and activation or inactivation of a gene. There are three major epigenetic mechanisms: DNA methylation, histone modifications, and microRNAs. The relationship between genetics, epigenetics, and peri-implantitis has been the subject of interest in the recent years; therefore, we aim in this chapter to present the state of the art on the role of genetic and epigenetic mechanisms in peri-implantitis.
16.	Baş, Yağmur, et al. (författare) Preparation and Characterization of Softwood and Hardwood Nanofibril Hydrogels: Toward Wound Dressing Applications 2023 Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 24:12, s. 5605-5619 Tidskriftsartikel (refereegranskat)abstract Hydrogels of cellulose nanofibrils (CNFs) are promising wound dressing candidates due to their biocompatibility, high water absorption, and transparency. Herein, two different commercially available wood species, softwood and hardwood, were subjected to TEMPO-mediated oxidation to proceed with delignification and oxidation in a one-pot process, and thereafter, nanofibrils were isolated using a high-pressure microfluidizer. Furthermore, transparent nanofibril hydrogel networks were prepared by vacuum filtration. Nanofibril properties and network performance correlated with oxidation were investigated and compared with commercially available TEMPO-oxidized pulp nanofibrils and their networks. Softwood nanofibril hydrogel networks exhibited the best mechanical properties, and in vitro toxicological risk assessment showed no detrimental effect for any of the studied hydrogels on human fibroblast or keratinocyte cells. This study demonstrates a straightforward processing route for direct oxidation of different wood species to obtain nanofibril hydrogels for potential use as wound dressings, with softwood having the most potential.
17.	Ferrantino, Luca, et al. (författare) Aesthetic Outcomes of Non-functional Immediately Restored Single Post-extraction Implants with and without Connective Tissue Graft: A Multicenter Randomized Controlled Trial. 2021 Ingår i: Clinical oral implants research. - : Wiley. - 1600-0501 .- 0905-7161. ; 32:6, s. 684-694 Tidskriftsartikel (refereegranskat)abstract To compare the one-year aesthetic results of flapless single implants, placed in fresh extraction sockets with bone replacement and immediate provisional restoration with or without a connective tissue graft (CGT).The present study proposes a partially blinded multicenter parallel randomized controlled trial, where computer-generated tables were used for central randomization to allocate treatments. 59 out of the 60 patients screened by eight private practices in Northern Italy fulfilled the inclusion criteria. Immediate implants was placed in a fresh extraction socket with a non-functional immediate provisional restoration with (Test group) or without (Control group) a CGT. The primary outcome variable was the implant Crown Aesthetic Index (ICAI) at the 1-year follow-up.ICAI for the 59 randomized patients (Test group = 31, Control group = 28) at the 1-year follow-up was 4.69 (95% CI = 3.16 - 6.22) for the Test group and 3.45 (95%CI = 1.83-5.08) for the Control group, without statistically significant difference between the two groups (p=0.086). One implant failure was recorded in each group, resulting in an implant survival rate of 96.8% [95%CI = 83.3 - 99.9] for the Test group and 96.4% [95%CI = 81.7 -99.9] for the Control group. Other secondary outcome variables and complication rates were comparable across the two groups.Within the limitations of the present clinical trial, the results suggested that the adjunct use of CTG is not mandatory to achieve successful aesthetic outcomes for a well-planned immediate implant placement with immediate non-functional provisional restoration in a fresh extraction socket.
18.	Ghandour, Salim, et al. (författare) Optimization of titanium spinal cages to maximize synthetic graft content in composite implants 2022 Konferensbidrag (refereegranskat)abstract Spinal fusion is the gold standard for treating patients with degenerative disc disease. Titanium alloys and PEEK are the two most common materials used to manufacture cages for spinal fusion, used to maintain disc height while the vertebrae fuse. Other materials, such as morselised bone, may be added to the cage to enhance the bioactivity. A monetite-based calcium phosphate has (as a composite implant in combination with titanium) shown potentially osteoinductive properties and may be a synthetic alternative to bone graft. Maximizing the ratio of calcium phosphate to titanium could be desirable to maximize bone ingrowth and fusion. Further, the calcium phosphate can be incorporated into the cage and stored ahead of surgery. The aim of this study was to topologically optimize cervical spine implants to incorporate a bioactive but mechanically weak material such as calcium phosphate.
19.	Ichioka, Yuki, et al. (författare) Changes in epigenetic pattern in osteoblasts in response to surface characteristics. 2020 Ingår i: Virtual Osteology Symposium USA. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Objective: The overall aim of the current project was to investigate the influence of titanium and titanium surface characteristics on epigenetic mechanisms. Materials & Methods: An osteoblast-like cells (MG63) was incubated on glass, smooth titanium and rough titanium respectively for 0,1,6 and 24 h. The presence of double stranded DNA damage, DNA repair and epigenetic markers were investigated using immunofluorescence. Results: The percentage of total Chk2 positive cells, which indicate DNA repair, was 0% on the rough titanium surfaces at all time points, in comparison to glass and smooth titanium. Regarding DNA damage, total -H2AX positive cells on the rough titanium gradually decreased as incubation time increased, on the contrary to smooth titanium. For epigenetic markers related to the DNA damage/repair pathway, rough titanium surface showed the lower percentage of AcH3 positive cells compared to glass and smooth titanium surface. Conclusions: The findings in the current study show that titanium surface characteristics indeed influence DNA damage and the DNA repair pathway, including epigenetic factors.
20.	Ichioka, Yuki, et al. (författare) Epigenetic changes of osteoblasts in response to titanium surface characteristics. 2021 Ingår i: Journal of biomedical materials research. Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 109:2, s. 170-180 Tidskriftsartikel (refereegranskat)abstract We aimed to investigate the influence of titanium surface characteristics on epigenetic mechanisms and DNA damage/repair pathways. Osteoblast-like cells (MG63) were incubated on glass, smooth titanium, and minimally rough titanium discs, respectively, for 0, 1, 6, and 24hr. The presence of double-stranded DNA damage (γH2AX), DNA repair (Chk2), and epigenetic markers (AcH3 & DNMT1) were investigated using immunofluorescence. There were no Chk2-positive cells on the minimally rough titanium surfaces at all-time points, in comparison to glass and smooth titanium. Total γH2AX-positive cells on minimally rough titanium gradually decreased as incubation time increased, on the contrary to smooth titanium. Minimally rough titanium surfaces induced cytoplasmic staining of DNMT1 up to 99% at 24hr. For epigenetic markers related to the DNA damage/repair pathway, minimally rough titanium surfaces showed the lower percentage of AcH3-positive cells compared to glass and smooth titanium surface. The findings in the current study show that titanium surface characteristics indeed influence DNA damage and the DNA repair pathway, including epigenetic factors.
21.	Khouly, Ismael, et al. (författare) The role of epigenetics in periodontal and systemic diseases and smoking: A systematic review 2021 Ingår i: Applied Sciences (Switzerland). - : MDPI AG. - 2076-3417. ; 11:11 Tidskriftsartikel (refereegranskat)abstract The aims of this systematic review were to identify and synthesize the evidence for an association in DNA methylation/histone modifications between periodontal diseases and systemic diseases/smoking. Electronic database searches using relevant search terms in PubMed, Embase, MEDLINE, CINAHL, Web of Science, Scopus, and SciELO, and manual searches, were independently conducted to identify articles meeting the inclusion criteria. Nine studies of 1482 participants were included. Periodontitis was compared to metabolic disorders, rheumatoid arthritis (RA), cancer, and smokers, as well as healthy controls. Substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology was found. IL6 and TNF were modified similarly in RA and periodontitis. While TIMP-3 and GSTP-1 were significantly lower in periodontitis patients and controls than in cancer, SOCS-1, RMI2, CDH1, and COX2 were modified similarly in both cancer and periodontitis. While TLR4 in and CXCL8 were affected in periodontitis independent of smoking habit, smoking might change the transcription and methylation states of ECM organization-related genes, which exacerbated the periodontal condition. There was some evidence, albeit inconsistent, for an association between DNA methylation and periodontal diseases and systemic diseases or smokers compared to healthy patients or non-smokers.
22.	Mellgren, Torbjörn, 1986-, et al. (författare) Guided bone tissue regeneration using a hollow calcium phosphate based implant in a critical size rabbit radius defect 2021 Ingår i: Biomedical Materials. - : Institute of Physics Publishing (IOPP). - 1748-6041 .- 1748-605X. ; 16:3 Tidskriftsartikel (refereegranskat)abstract Long bone fractures are common and sometimes difficult to treat. Autologous bone (AB), bovine bone and calcium phosphates are used to stimulate bone growth with varying results. In the present study, a calcium phosphate cement (CPC) that previously showed promising grafting capabilities was evaluated for the first time in a long bone defect. A radius defect of 20 mm was created in 20 rabbits. The defect was filled by either a hollow CPC implant that had been manufactured as a replica of a rabbit radius through indirect 3D printing, or by particulate AB as control. Defect filling and bone formation was evaluated after 12 weeks by combining micro computed tomography (mu CT) and scoring of 3D images, together with histomorphometry and histology. The mu CT and histomorphometric evaluations showed a similar amount of filling of the defect (combining graft and bone) between the CPC and AB group, but the scoring of 3D images showed that the filling in the CPC group was significantly larger. Histologically the AB graft could not be distinguished from the new bone. The AB treated defects were found to be composed of more bone than the CPC group, including reorganised cancellous and cortical bone. Both the CPC and AB material was associated with new bone formation, also in the middle of the defect, which could result in closing of the otherwise critically sized gap. This study shows the potential for an indirectly 3D printed implant in guided bone regeneration in critically sized long bone defects.
23.	Apelgren, Peter, et al. (författare) Vascularization of tissue engineered cartilage-Sequential in vivo MRI display functional blood circulation 2021 Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 276 Tidskriftsartikel (refereegranskat)abstract Establishing functional circulation in bioengineered tissue after implantation is vital for the delivery of oxygen and nutrients to the cells. Native cartilage is avascular and thrives on diffusion, which in turn depends on proximity to circulation. Here, we investigate whether a gridded three-dimensional (3D) bioprinted construct would allow ingrowth of blood vessels and thus prove a functional concept for vascularization of bioengineered tissue. Twenty 10 x 10 x 3-mm 3Dbioprinted nanocellulose constructs containing human nasal chondrocytes or cell-free controls were subcutaneously implanted in 20 nude mice. Over the next 3 months, the mice were sequentially imaged with a 7 T small-animal MRI system, and the diffusion and perfusion parameters were analyzed. The chondrocytes survived and proliferated, and the shape of the constructs was well preserved. The diffusion coefficient was high and well preserved over time. The perfusion and diffusion patterns shown by MRI suggested that blood vessels develop over time in the 3D bioprinted constructs; the vessels were confirmed by histology and immunohistochemistry. We conclude that 3D bioprinted tissue with a gridded structure allows ingrowth of blood vessels and has the potential to be vascularized from the host. This is an essential step to take bioengineered tissue from the bench to clinical practice.
24.	Pettersen, Emily, 1996, et al. (författare) Electrical stimulation to promote osseointegration of bone anchoring implants: a topical review 2022 Ingår i: Journal of Neuroengineering and Rehabilitation. - : Springer Science and Business Media LLC. - 1743-0003. ; 19:1 Tidskriftsartikel (refereegranskat)abstract Electrical stimulation has shown to be a promising approach for promoting osseointegration in bone anchoring implants, where osseointegration defines the biological bonding between the implant surface and bone tissue. Bone-anchored implants are used in the rehabilitation of hearing and limb loss, and extensively in edentulous patients. Inadequate osseointegration is one of the major factors of implant failure that could be prevented by accelerating or enhancing the osseointegration process by artificial means. In this article, we reviewed the efforts to enhance the biofunctionality at the bone-implant interface with electrical stimulation using the implant as an electrode. We reviewed articles describing different electrode configurations, power sources, and waveform-dependent stimulation parameters tested in various in vitro and in vivo models. In total 55 English-language and peer-reviewed publications were identified until April 2020 using PubMed, Google Scholar, and the Chalmers University of Technology Library discovery system using the keywords: osseointegration, electrical stimulation, direct current and titanium implant. Thirteen of those publications were within the scope of this review. We reviewed and compared studies from the last 45 years and found nonuniform protocols with disparities in cell type and animal model, implant location, experimental timeline, implant material, evaluation assays, and type of electrical stimulation. The reporting of stimulation parameters was also found to be inconsistent and incomplete throughout the literature. Studies using in vitro models showed that osteoblasts were sensitive to the magnitude of the electric field and duration of exposure, and such variables similarly affected bone quantity around implants in in vivo investigations. Most studies showed benefits of electrical stimulation in the underlying processes leading to osseointegration, and therefore we found the idea of promoting osseointegration by using electric fields to be supported by the available evidence. However, such an effect has not been demonstrated conclusively nor optimally in humans. We found that optimal stimulation parameters have not been thoroughly investigated and this remains an important step towards the clinical translation of this concept. In addition, there is a need for reporting standards to enable meta-analysis for evidence-based treatments.
25.	van Zyl, Martin, et al. (författare) Injectable conductive hydrogel restores conduction through ablated myocardium 2020 Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1045-3873 .- 1540-8167. ; 31:12, s. 3293-3301 Tidskriftsartikel (refereegranskat)abstract Introduction Therapies for substrate-related arrhythmias include ablation or drugs targeted at altering conductive properties or disruption of slow zones in heterogeneous myocardium. Conductive compounds such as carbon nanotubes may provide a novel personalizable therapy for arrhythmia treatment by allowing tissue homogenization. Methods A nanocellulose carbon nanotube-conductive hydrogel was developed to have conduction properties similar to normal myocardium. Ex vivo perfused canine hearts were studied. Electroanatomic activation mapping of the epicardial surface was performed at baseline, after radiofrequency ablation, and after uniform needle injections of the conductive hydrogel through the injured tissue. Gross histology was used to assess distribution of conductive hydrogel in the tissue. Results The conductive hydrogel viscosity was optimized to decrease with increasing shear rate to allow expression through a syringe. The direct current conductivity under aqueous conduction was 4.3 x 10(-1) S/cm. In four canine hearts, when compared with the homogeneous baseline conduction, isochronal maps demonstrated sequential myocardial activation with a shift in direction of activation to surround the edges of the ablated region. After injection of the conductive hydrogel, isochrones demonstrated conduction through the ablated tissue with activation restored through the ablated tissue. Gross specimen examination demonstrated retention of the hydrogel within the tissue. Conclusions This proof-of-concept study demonstrates that conductive hydrogel can be injected into acutely disrupted myocardium to restore conduction. Future experiments should focus on evaluating long-term retention and biocompatibility of the hydrogel through in vivo experimentation.
26.	von Mentzer, Ula, 1995, et al. (författare) Biomaterial Integration in the Joint: Pathological Considerations, Immunomodulation, and the Extracellular Matrix 2022 Ingår i: Macromolecular Bioscience. - : Wiley. - 1616-5195 .- 1616-5187. ; 22:7 Forskningsöversikt (refereegranskat)abstract Defects of articular joints are becoming an increasing societal burden due to a persistent increase in obesity and aging. For some patients suffering from cartilage erosion, joint replacement is the final option to regain proper motion and limit pain. Extensive research has been undertaken to identify novel strategies enabling earlier intervention to promote regeneration and cartilage healing. With the introduction of decellularized extracellular matrix (dECM), researchers have tapped into the potential for increased tissue regeneration by designing biomaterials with inherent biochemical and immunomodulatory signals. Compared to conventional and synthetic materials, dECM-based materials invoke a reduced foreign body response. It is therefore highly beneficial to understand the interplay of how these native tissue-based materials initiate a favorable remodeling process by the immune system. Yet, such an understanding also demands increasing considerations of the pathological environment and remodeling processes, especially for materials designed for early disease intervention. This knowledge will avoid rejection and help predict complications in conditions with inflammatory components such as arthritides. This review outlines general issues facing biomaterial integration and emphasizes the importance of tissue-derived macromolecular components in regulating essential homeostatic, immunological, and pathological processes to increase biomaterial integration for patients suffering from joint degenerative diseases.
27.	Berglund, Fanny, et al. (författare) Evidence for wastewaters as environments where mobile antibiotic resistance genes emerge 2023 Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 6 Tidskriftsartikel (refereegranskat)abstract The emergence and spread of mobile antibiotic resistance genes (ARGs) in pathogens have become a serious threat to global health. Still little is known about where ARGs gain mobility in the first place. Here, we aimed to collect evidence indicating where suchinitial mobilizationevents of clinically relevant ARGs may have occurred. We found that the majority of previously identified origin species did not carry the mobilizing elements that likely enabled intracellular mobility of the ARGs, suggesting a necessary interplay between different bacteria. Analyses of a broad range of metagenomes revealed that wastewaters and wastewater-impacted environments had by far the highest abundance of both origin species and corresponding mobilizing elements. Most origin species were only occasionally detected in other environments. Co-occurrence of origin species and corresponding mobilizing elements were rare in human microbiota. Our results identify wastewaters and wastewater-impacted environments as plausible arenas for the initial mobilization of resistance genes.
28.	Fornell, Anna, et al. (författare) Acoustic focusing of beads and cells in hydrogel droplets 2021 Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1 Tidskriftsartikel (refereegranskat)abstract The generation of hydrogel droplets using droplet microfluidics has emerged as a powerful tool with many applications in biology and medicine. Here, a microfluidic system to control the position of particles (beads or astrocyte cells) in hydrogel droplets using bulk acoustic standing waves is presented. The chip consisted of a droplet generator and a 380 µm wide acoustic focusing channel. Droplets comprising hydrogel precursor solution (polyethylene glycol tetraacrylate or a combination of polyethylene glycol tetraacrylate and gelatine methacrylate), photoinitiator and particles were generated. The droplets passed along the acoustic focusing channel where a half wavelength acoustic standing wave field was generated, and the particles were focused to the centre line of the droplets (i.e. the pressure nodal line) by the acoustic force. The droplets were cross-linked by exposure to UV-light, freezing the particles in their positions. With the acoustics applied, 89 ± 19% of the particles (polystyrene beads, 10 µm diameter) were positioned in an area ± 10% from the centre line. As proof-of-principle for biological particles, astrocytes were focused in hydrogel droplets using the same principle. The viability of the astrocytes after 7 days in culture was 72 ± 22% when exposed to the acoustic focusing compared with 70 ± 19% for samples not exposed to the acoustic focusing. This technology provides a platform to control the spatial position of bioparticles in hydrogel droplets, and opens up for the generation of more complex biological hydrogel structures.
29.	Abbasi Aval, Negar, et al. (författare) Assessing the Layer-by-Layer Assembly of Cellulose Nanofibrils and Polyelectrolytes in Pancreatic Tumor Spheroid Formation 2023 Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 11:11 Tidskriftsartikel (refereegranskat)abstract Three-dimensional (3D) tumor spheroids are regarded as promising models for utilization as preclinical assessments of chemo-sensitivity. However, the creation of these tumor spheroids presents challenges, given that not all tumor cell lines are able to form consistent and regular spheroids. In this context, we have developed a novel layer-by-layer coating of cellulose nanofibril–polyelectrolyte bilayers for the generation of spheroids. This technique builds bilayers of cellulose nanofibrils and polyelectrolytes and is used here to coat two distinct 96-well plate types: nontreated/non-sterilized and Nunclon Delta. In this work, we optimized the protocol aimed at generating and characterizing spheroids on difficult-to-grow pancreatic tumor cell lines. Here, diverse parameters were explored, encompassing the bilayer count (five and ten) and multiple cell-seeding concentrations (10, 100, 200, 500, and 1000 cells per well), using four pancreatic tumor cell lines—KPCT, PANC-1, MiaPaCa-2, and CFPAC-I. The evaluation includes the quantification (number of spheroids, size, and morphology) and proliferation of the produced spheroids, as well as an assessment of their viability. Notably, our findings reveal a significant influence from both the number of bilayers and the plate type used on the successful formation of spheroids. The novel and simple layer-by-layer-based coating method has the potential to offer the large-scale production of spheroids across a spectrum of tumor cell lines.
30.	Abbasi Aval, Negar, et al. (författare) Evaluating the Impact of Positively Charged Polyelectrolyte Molecular Weightand Bilayer Number on Tumor Spheroid Formation in the Interaction with Negatively Charged Cellulose Nanofibrils in layer by layer assembly 2023 Annan publikation (övrigt vetenskapligt/konstnärligt)
31.	Abbasi Aval, Negar, 1986- (författare) Utilizing Biopolymers in 3D Tumor Modeling and Tumor Diagnosis 2023 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Cancer represents a significant global public health challenge and ranks as the second mostcommon cause of death in the United States. The onset of cancer entails an initial phasewhere cells lose their polarity and disconnect from the normal basement membrane, allowingthem to form distinct three-dimensional (3D) configurations that interact with adjacent cellsand the surrounding microenvironment. Cells grown in 2D monolayers demonstrate differentgene expression patterns and different activation of signaling pathways compared to cellscultivated within the natural structure of tumor tissue of the same cell type. Multicellulartumor spheroids (MCTS) are extensively investigated as a well-studied model of organotypiccancer. These spheroids are formed by tumor cells, either alone or in combination with othercell types, and they can be created with or without the application of supportive scaffolds.The MCTSs are also considered promising models for preclinical assessments of chemosensitivity.However, the creation of these tumor spheroids presents challenges, as not alltumor cell lines can consistently form regular spheroids.Cellulose nanofibrils (CNF) have become essential as a sustainable and environmentallyfriendly material. For example, thin films, with inherent mechanical properties, and flexibility,offer versatility across various applications. Also known for its biocompatibility and non-toxicnature, native CNF is a natural option to use. Its fibrous structure closely mimics the collagenmatrix in human tissue, showing potential as an effective scaffold for 3D cell culture. In thisregard, an innovative Layer-by-Layer (LbL) coating technique using CNF-polyelectrolytebilayers was investigated to generate spheroids. This method constructs bilayers of CNFand polyelectrolytes and can coat various surfaces. In this thesis, the first focus was ondemonstrating the spheroid formation capability using low molecular weight polyelectrolytesin LbL assembly. Secondly, an investigation was conducted involving embedding of LbLgrownspheroids in a decellularized extracellular matrix (ECM) aiming to determine howECM, possessing suitable mechanical characteristics, could influence the cancer stem celltraits in spheroids. Thirdly, the thesis demonstrated the utilization of LbL for capturing andreleasing of circulating tumor cells. Lastly, the shift from using low molecular weightpolyelectrolytes in the LbL assembly to high molecular weight counterparts and analyzingthe differences in spheroid formation abilities to assess the underlying differences inmolecular weights of the polyelectrolytes was explored. All-in-all, employing the CNF-basedLbL surface coating strategy explored in the thesis has proven to be promising for thedevelopment of spheroid models closely resembling in vivo conditions and holds significantpotential for applications in drug development.
32.	Abdollahi, Farnoosh, et al. (författare) Angiogenesis in bone tissue engineering via ceramic scaffolds: A review of concepts and recent advancements 2024 Ingår i: Biomaterials Advances. - : Elsevier BV. - 2772-9516 .- 2772-9508. ; 159 Forskningsöversikt (refereegranskat)abstract Due to organ donor shortages, long transplant waitlists, and the complications/limitations associated with auto and allotransplantation, biomaterials and tissue-engineered models are gaining attention as feasible alternatives for replacing and reconstructing damaged organs and tissues. Among various tissue engineering applications, bone tissue engineering has become a promising strategy to replace or repair damaged bone. We aimed to provide an overview of bioactive ceramic scaffolds in bone tissue engineering, focusing on angiogenesis and the effect of different biofunctionalization strategies. Different routes to angiogenesis, including chemical induction through signaling molecules immobilized covalently or non-covalently, in situ secretion of angiogenic growth factors, and the degradation of inorganic scaffolds, are described. Physical induction mechanisms are also discussed, followed by a review of methods for fabricating bioactive ceramic scaffolds via microfabrication methods, such as photolithography and 3D printing. Finally, the strengths and weaknesses of the commonly used methodologies and future directions are discussed.
33.	Abiodun Daramola, Olamide, et al. (författare) Biocompatible liposome and chitosan-coated CdTe/CdSe/ZnSe multi-core-multi-shell fluorescent nanoprobe for biomedical applications 2024 Ingår i: Journal of Photochemistry and Photobiology A. - : Elsevier. - 1010-6030 .- 1873-2666. ; 454 Tidskriftsartikel (refereegranskat)abstract Cadmium telluride (CdTe) semiconductor quantum dots (QDs) are brightly luminescent nanocrystals that have emerged as a new class of fluorescent probes for in vivo bioimaging and theranostic applications. CdTe QDs toxicity to normal human cells is minimized by coating with a less toxic ZnS and ZnSe shell forming a core–shell nanostructure. However, coating with ZnS or ZnSe shell is insufficient to prevent the leaching of toxic Cd metal ions. To further minimize toxicity, thiol dual capped CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots were coated with nanoliposome or liposome vesicles (CdTe/CdSe/ZnSe@liposome) and chitosan nanoparticles (CdTe/CdSe/ZnSe@ChitNPs) and their biocompatibility on HeLa and Vero cells were investigated. Different spectroscopic and microscopic techniques were used to elucidate nanocomposites' optical, morphological, and physicochemical properties. The coating of CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots were conducted at different formulations (F1, F2 and F3) and results from the fluorescence studies show that F3 demonstrated the best interaction for both liposome and ChitNPs composite. Exposure to 12 h UV illumination studies also reveals that CdTe/CdSe/ZnSe@liposome shows an enhancement in fluorescence compared to CdTe/CdSe/ZnSe@ChitNPs. The cytotoxicity of the formulations towards HeLa and Vero cells also depicted minimal toxicity compared to CdTe/CdSe/ZnSe QDs that shows much higher toxicity (IC50 = 0.09381 mg/ml). It was further observed that liposome coated multi-core-multi-shell QDs@F2 demonstrated lower toxicity (IC50 = 0.4364 mg/ml) compared to ChitNPs coated multi-core-multi-shell QDs@F2 (IC50 = 0.1618 mg/ml). Results from the florescence imaging studies reveal that CdTe/CdSe/ZnSe-multi-core-multi-shell QDs liposomes and ChitNPs composite retained most of their fluorescence and properties and could easily be tracked in cells and visualized around the nucleus. This indicates the successful internalization of the QDs in the cytosol. Therefore, these results shows that coating CdTe multi-core-mutli-shell QDs with liposomes and ChitNPs produce better biocompatibility compared to uncoated multi-core–shell QDs. However, liposome coated CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots show better optical properties, photostability and biocompatibility compared to CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots with ChitNPs coating. These particles therefore show good promise in cell-labelling and drug delivery studies.
34.	Adamo, Christin S., et al. (författare) EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis 2022 Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 109:12, s. 2230-2252 Tidskriftsartikel (refereegranskat)abstract EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1-/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis.
35.	Adolfsson, Karin H., et al. (författare) In Vivo Versus In Vitro Degradation of a 3D Printed Resorbable Device for Ligation of Vascular Tissue in Horses 2021 Ingår i: Macromolecular Bioscience. - : Wiley. - 1616-5187 .- 1616-5195. ; 21:10 Tidskriftsartikel (refereegranskat)abstract A resorbable 3D printed polydioxanone (PDO) device is manufactured to facilitate ligation of vascular tissue during surgery. The device must provide sufficient mechanical performance throughout the healing period. Therefore, degradation and mechanical performance of the device are investigated as a function of in vivo and in vitro aging. During aging the PDO device released cyclic and linear water-soluble products. In vivo aging resulted in higher relative number of linear oligomers in comparison to in vitro aging. A major loss of mechanical performance is observed after only 10 days in vivo and the Young’s modulus (E) and tensile strength at break (σb) decreased by 28% and 54%, respectively. This is in contrast to in vitro aging, where no loss of mechanical properties is observed during the same period. The in vivo aged devices exhibit clear holes in the matrices after 28 days, while apparent cracks are observed first after 140 days in vitro. These results highlight the sensitivity of the degradation process of resorbable devices with regards to the interactions of the device with the surrounding environment (tissues) and demonstrate the importance of in vivo testing as compliment to in vitro testing before clinical use of devices.
36.	Afewerki, Samson, et al. (författare) Advances in dual functional antimicrobial and osteoinductive biomaterials for orthopaedic applications 2020 Ingår i: Nanomedicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 24 Forskningsöversikt (refereegranskat)abstract A vast growing problem in orthopaedic medicine is the increase of clinical cases with antibiotic resistant pathogenic microbes, which is predicted to cause higher mortality than all cancers combined by 2050. Bone infectious diseases limit the healing ability of tissues and increase the risk of future injuries due to pathologic tissue remodelling. The traditional treatment for bone infections has several drawbacks and limitations, such as lengthy antibiotic treatment, extensive surgical interventions, and removal of orthopaedic implants and/or prosthesis, all of these resulting in long-term rehabilitation. This is a huge burden to the public health system resulting in increased healthcare costs. Current technologies e.g. co-delivery systems, where antibacterial and osteoinductive agents are delivered encounter challenges such as site-specific delivery, sustained and prolonged release, and biocompatibility. In this review, these aspects are highlighted to promote the invention of the next generation biomaterials to prevent and/or treat bone infections and promote tissue regeneration.
37.	Agar, David (författare) Spear study misses the point: a critique of the Ennos and Chan fire-hardening study, concerning wood material representation in archaeological finds and generalized conclusions 2021 Ingår i: Biology Letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 17 Tidskriftsartikel (refereegranskat)
38.	Ahmed, Kirstin, 1974, et al. (författare) Experimental Validation of an ITAP Numerical Model and the Effect of Implant Stem Stiffness on Bone Strain Energy 2020 Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 1573-9686 .- 0090-6964. Tidskriftsartikel (refereegranskat)abstract The Intraosseous Transcutaneous Amputation Prosthesis (ITAP) offers transfemoral amputees an ambulatory method potentially reducing soft tissue complications seen with socket and stump devices. This study validated a finite element (in silico) model based on an ITAP design and investigated implant stem stiffness influence on periprosthetic femoral bone strain. Results showed good agreement in the validation of the in silico model against the in vitro results using uniaxial strain gauges and Digital Image Correlation (DIC). Using Strain Energy Density (SED) thresholds as the stimulus for adaptive bone remodelling, the validated model illustrated that: (a) bone apposition increased and resorption decreased with increasing implant stem flexibility in early stance; (b) bone apposition decreased (mean change = − 9.8%) and resorption increased (mean change = 20.3%) from distal to proximal in most stem stiffness models in early stance. By engineering the flow of force through the implant/bone (e.g. by changing material properties) these results demonstrate how periprosthetic bone remodelling, thus aseptic loosening, can be managed. This paper finds that future implant designs should be optimised for bone strain under a variety of relevant loading conditions using finite element models to maximise the chances of clinical success.
39.	Akhmetova, Alma, et al. (författare) Highly elastic and water stable zein microfibers as a potential drug delivery system for wound healing 2020 Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 12:5 Tidskriftsartikel (refereegranskat)abstract The development of biomaterials for wound healing applications requires providing a number of properties, such as antimicrobial action, facilitation of cell proliferation, biocompatibility and biodegradability. The aim of the present study was to investigate morphological and mechanical properties of zein-based microfibers, ultimately aimed at creating an environment suitable for wound healing. This was achieved through co-axial electrospinning of core–shell microfibers, with zein protein in the core and polyethylene oxide (PEO) in the shell. Small amounts of PEO or stearic acid were additionally incorporated into the fiber core to modify the morphology and mechanical properties of zein fibers. The presence of PEO in the core was found to be essential for the formation of tubular fibers, whereas PEO in the shell enhanced the stability of the microfibers in water and ensured high elasticity of the microfiber mats. Tetracycline hydrochloride was present in an amorphous form within the fibers, and displayed a burst release as a result of pore-formation in the fibers. The developed systems exhibited antimicrobial activity against Staphylococcus aureus and Escherichia coli, and showed no cytotoxic effect on fibroblasts. Biocompatibility, antimicrobial activity and favorable morphological and mechanical properties make the developed zein-based microfibers a potential biomaterial for wound healing purposes.
40.	Akinwekomi, Akeem Damilola, et al. (författare) Tunability of mechanical and biodegradation properties of zinc-based biomaterial with calcium Micronutrient alloying 2023 Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier Ltd. - 1751-6161 .- 1878-0180. ; 140 Tidskriftsartikel (refereegranskat)abstract Biodegradable metals are being investigated as temporary implants that dissolve safely in the body after bone regeneration. Zinc (Zn) has an intermediate biodegradation rate between magnesium and stainless steels, yet its degradation rate is too slow to function as a temporary orthopedic implant. Alloying with nutrient elements is considered a strategy to tune its mechanical properties and in vivo biodegradability. Zn/calcium (Zn/Ca) alloys (with 0.5, 1, and 2 wt% Ca) were processed by spark plasma sintering and their microstructure, mechanical, and biodegradation properties were investigated. Ca was distributed in the grain boundary regions of Zn due to its low miscibility in Zn. Furthermore, the corrosion rates of Zn/Ca alloys determined from linear polarization measurements (0.164–0.325 mm/yr) accelerated by at least 10% compared with pure sintered Zn (0.149 mm/yr) with simultaneous dissolution of Zn and Ca, as verified from X-ray diffraction analysis of the corrosion products. The alloy specimens exhibited hardness (52–58 HV) and compressive strength (93–119 MPa) comparable with those of human cortical and cancellous bones (49 HV; 90–209 MPa). This study demonstrated the tunability of the mechanical and biodegradation properties of Zn-based materials by alloying them with a nutrient element for potential application as temporary orthopedic implants.
41.	Akman, Adnan, et al. (författare) Effect of minor gallium addition on corrosion, passivity, and antibacterial behaviour of novel β-type Ti–Nb alloys 2023 Ingår i: Journal of Materials Research and Technology. - 2238-7854. ; 25, s. 4110-4124 Tidskriftsartikel (refereegranskat)abstract Metastable Ti–Nb alloys are promising bone-implant materials due to improved mechanical biofunctionality and biocompatibility. To overcome increasing bacterial infection risk, alloying with antibacterial elements is a promising strategy. This study investigates the effect of minor gallium (Ga) additions (4, 8 wt% Ga) to as-cast and solution-treated β-type Ti–45Nb-based alloy (96(Ti–45Nb)-4Ga, 92(Ti–45Nb)-8Ga (wt.%)) on corrosion and passive film properties, as well as cytocompatibility and antibacterial activity. The electrochemical properties were evaluated by potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and Mott-Schottky analyses in phosphate-buffered saline (PBS). X-ray photoelectron spectroscopy (XPS) was performed to analyze the chemical composition of passive films. Early adhesion and viability of macrophages and Staphylococcus aureus were assessed by nucleocounting and colony-forming unit counting, respectively. The results showed that high corrosion resistance and passive film properties of Ti–45Nb are retained and even slightly improved with Ga. EIS results revealed that Ga addition improves the passive film resistance. XPS measurements of 92(Ti–45Nb)-8Ga show that the passive film contains Ti-, Nb- and Ga-based oxides, implying the formation of mixed (Ti–Nb-Ga) oxides. In addition, marginal Ga ion release rate was detected under free corrosion conditions. Therefore, it can be assumed that Ga species may contribute to passive film formation on Ga-containing alloys. The 92(Ti–45Nb)-8Ga elicited an antibacterial effect against S. aureus compared to cp-Ti at 4 h. Moreover, Ga-containing alloys showed good cytocompatibility with THP-1 macrophages at 24 h. In conclusion, it was demonstrated that Ga additions to Ti–45Nb are beneficial to corrosion resistance and showed promising initial host and bacterial interactions.
42.	AlAgil, Jumana, et al. (författare) Risk of postoperative bleeding after dental extraction in patients on antiplatelet therapy: systematic review and meta-analysis. 2023 Ingår i: Oral surgery, oral medicine, oral pathology and oral radiology. - 2212-4411. Tidskriftsartikel (refereegranskat)abstract To determine the risk of bleeding after minor extraction in patients on different antiplatelet therapy (APT) regimens.A search was conducted using PubMed and Google Scholar. Thirty-five papers were included in the systematic review, of which 23 papers provided the requisite information for meta-analysis. Subgroups were created based on the controls, as follows: (1) no control, (2) healthy control, and (3) interrupted APT control. In a meta-analysis, the studies were further subdivided into immediate and delayed bleeding.No immediate or delayed bleeding risk was found in patients treated with aspirin vs healthy controls (relative risk [RR] = 1.26; P = .5 and RR = 2.17; P = .09, respectively). A higher immediate bleeding was recorded for patients on single nonaspirin APT vs those in the healthy population (RR = 3.72; P = .0009). A high risk of bleeding was recorded in patients receiving dual APT compared with healthy controls for immediate (RR = 10.3; P < .0001) and delayed (RR = 7.72; P = .001) bleeding. Dual APT continuation showed a higher risk of immediate bleeding (RR = 2.13) than interrupted APT, but the difference was insignificant (P = .07).Dental extraction can be performed safely in patients on aspirin monotherapy. In contrast, patients receiving dual APT should be considered at risk for immediate and continued bleeding.
43.	Alizadehgharib, Sara, et al. (författare) The effects of the dental methacrylates TEGDMA, Bis-GMA, and UDMA on neutrophils in vitro. 2020 Ingår i: Clinical and experimental dental research. - : Wiley. - 2057-4347. ; 6:4, s. 439-447 Tidskriftsartikel (refereegranskat)abstract The prevalent usage of methacrylates in modern dentistry demands good knowledge of their biological impacts. While there have been several studies demonstrating the effects of different methacrylic monomers on mononuclear white blood cells, very little is known about the effects caused by these monomers on neutrophilic granulocytes. The objective of this study was to add novel knowledge about how neutrophils are affected by exposure to triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), and bisphenol A glycol dimethacrylate (Bis-GMA) alone or in combinations.Isolated neutrophils were cultured in the presence or absence of methacrylates. The IL-8 release was measured using a DuoSet ELISA development kit. Apoptosis and necrosis were analyzed using flow cytometry. The formation of neutrophil extracellular traps (NETs) was investigated using Sytox green DNA staining combined with microscopically examination of released DNA and myeloperoxidase (MPO).The release of IL-8 was significantly increased after exposure to TEGDMA, Bis-GMA, UDMA, or TEGDMA in combination with Bis-GMA or UDMA compared to the unstimulated controls. Exposure to TEGDMA, UDMA, and Bis-GMA for 24hr separately or in combination did not affect apoptosis or necrosis of the exposed neutrophils. NET structures were formed by neutrophils after exposure to the different combinations of the methacrylates.The combination of TEGDMA and Bis-GMA had a synergistic proinflammatory effect on neutrophils by increasing the release of IL-8 and the formation of NET structures. The changes in the normal functions of neutrophils caused by methacrylate exposure may lead to altered inflammatory response and relate to previously reported adverse immune reactions caused by these substances.
44.	Alloisio, Marta, et al. (författare) Fracture of porcine aorta-Part 1 : symconCT fracture testing and DIC 2023 Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 167, s. 147-157 Tidskriftsartikel (refereegranskat)abstract Tissue failure and damage are inherent parts of vascular diseases and tightly linked to clinical events. Additionally, experimental set-ups designed to study classical engineering materials are suboptimal in the exploration of vessel wall fracture properties. The classical Compact Tension (CT) test was augmented to enable stable fracture propagation, resulting in the symmetry-constraint Compact Tension (symconCT) test, a suitable set-up for fracture testing of vascular tissue. The test was combined with Digital Image Correlation (DIC) to study tissue fracture in 45 porcine aorta specimens. Test specimens were loaded in axial and circumferential directions in a physiological solution at 37 & DEG;C. Loading the aortic vessel wall in the axial direction resulted in mode I tissue failure and a fracture path aligned with the circumferential vessel direction. Circumferential loading resulted in mode I-dominated failure with multiple deflections of the fracture path. The aorta ruptured at a principal Green-Lagrange strain of approximately 0.7, and strain rate peaks that develop ahead of the crack tip reached nearly 400 times the strain rate on average over the test specimen. It required approximately 70% more external work to fracture the aorta by circumferential than axial load; normalised with the fracture surface, similar energy levels are, however, observed. The symconCT test resulted in a stable fracture propagation, which, combined with DIC, provided a set-up for the in-depth analysis of vascular tissue failure. The high strain rates ahead of the crack tip indicate the significance of rate effects in the constitutive description of vascular tissue fracture.
45.	Alshammari, Hatem, et al. (författare) Antimicrobial Properties of Strontium Functionalized Titanium Surfaces for Oral Applications, A Systematic Review 2021 Ingår i: Coatings. - : MDPI. - 2079-6412. ; 11:7 Forskningsöversikt (refereegranskat)abstract The aim of this systematic review was to assess the current scientific evidence of the antimicrobial potential of strontium (Sr) when used to functionalize titanium (Ti) for oral applications. Out of an initial list of 1081 potentially relevant publications identified in three electronic databases (MEDLINE via PubMed, Scopus, and Cochrane) up to 1 February 2021, nine publications based on in vitro studies met the inclusion criteria. The antimicrobial potential of Sr was investigated on different types of functionalized Ti substrates, employing different application methods. Nine studies reported on the early, i.e., 6-24 h, and two studies on the late, i.e., 7-28 days, antimicrobial effect of Sr, primarily against Staphylococcus aureus (S. aureus) and/or Escherichia coli (E. coli). Sr-modified samples demonstrated relevant early antimicrobial potential against S. aureus in three studies; only one of which presented statistical significance values, while the other two presented only the percentage of antimicrobial rate and biofilm inhibition. A relevant late biofilm inhibition potential against S. aureus of 40% and 10%-after 7 and 14 days, respectively-was reported in one study. Combining Sr with other metal ions, i.e., silver (Ag), zinc (Zn), and fluorine (F), demonstrated a significant antimicrobial effect and biofilm inhibition against both S. aureus and E. coli. Sr ion release within the first 24 h was generally low, i.e., below 50 mu g/L and 0.6 ppm; however, sustained Sr ion release for up to 30 days, while maintaining up to 90% of its original content, was also demonstrated. Thus, in most studies included herein, Sr-functionalized Ti showed a limited immediate (i.e., 24 h) antimicrobial effect, likely due to a low Sr ion release; however, with an adequate Sr ion release, a relevant antimicrobial effect, as well as a biofilm inhibition potential against S. aureus-but not E. coli-was observed at both early and late timepoints. Future studies should assess the antimicrobial potential of Ti functionalized with Sr against multispecies biofilms associated with peri-implantitis.
46.	Aludden, Hanna, et al. (författare) Histological and histomorphometrical outcome after lateral guided bone regeneration augmentation of the mandible with different ratios of deproteinized bovine bone mineral and autogenous bone. A preclinical in vivo study 2020 Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 31:10, s. 1025-1036 Tidskriftsartikel (refereegranskat)abstract © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Objective: To test the hypotheses of no differences in (I) percentage of bone (POB), non-mineralized tissue (NMT), and deproteinized bovine bone mineral (DBBM), and (II) ingrowth of mineralized bone after lateral guided bone regeneration (GBR) augmentation of the mandible with different ratios of DBBM and particulate autogenous bone (PAB) at different time points. Material and methods: Twenty-four minipigs were randomly allocated into three groups. Lateral augmentation in 96 sites (4 in each animal) was performed unilaterally with a standardized quantity of grafting material in each animal with different ratios of DBBM and PAB (50:50, 75:25, 100:0) and autogenous bone block in combination with DBBM and covered with a collagen membrane. The percentage of different tissues in the graft and ingrowth of mineralized bone was assessed by histomorphometrical and histological analyses after 10, 20, and 30weeks, respectively. Results: The POB was 54% (50:50), 50% (75:25), and 48% (100:0) after 10weeks, 60% (50:50), 61% (75:25), and 60% (100:0) after 20weeks, and 63% (50:50), 62% (75:25), and 62% (100:0) after 30weeks. There was no significant difference between the groups at any time points. There was a significant increase in POB and a significant decrease in NMT for 75:25 and 100:0 from 10 to 30weeks. All ratios demonstrated a non-complete ingrowth of mineralized bone into the graft after 10weeks and complete mineralization after 30weeks. Conclusion: Within the limitations of the present study, it seems like addition of autogenous bone to DBBM for LRA did not affect the bone formation nor graft incorporation after 10–30weeks of healing. However, a prolonged healing time seems to result in an increased POB for all ratios.
47.	Amagat, Jordi, et al. (författare) Injectable 2D flexible hydrogel sheets for optoelectrical/biochemical dual stimulation of neurons 2023 Ingår i: Biomaterials Advances. - : Elsevier BV. - 2772-9516 .- 2772-9508. ; 146 Tidskriftsartikel (refereegranskat)abstract Major challenges in developing implanted neural stimulation devices are the invasiveness, complexity, and cost of the implantation procedure. Here, we report an injectable, nanofibrous 2D flexible hydrogel sheet-based neural stimulation device that can be non-invasively implanted via syringe injection for optoelectrical and biochemical dual stimulation of neuron. Specifically, methacrylated gelatin (GelMA)/alginate hydrogel nanofibers were mechanically reinforced with a poly(lactide-co-ε-caprolactone) (PLCL) core by coaxial electrospinning. The lubricant hydrogel shell enabled not only injectability, but also facile incorporation of functional nanomaterials and bioactives. The nanofibers loaded with photocatatlytic g-C3N4/GO nanoparticles were capable of stimulating neural cells via blue light, with a significant 36.3 % enhancement in neurite extension. Meanwhile, the nerve growth factor (NGF) loaded nanofibers supported a sustained release of NGF with well-maintained function to biochemically stimulate neural differentiation. We have demonstrated the capability of an injectable, hydrogel nanofibrous, neural stimulation system to support neural stimulation both optoelectrically and biochemically, which represents crucial early steps in a larger effort to create a minimally invasive system for neural stimulation.
48.	An, Rong, et al. (författare) Integrative studies of ionic liquid interface layers: bridging experiments, theoretical models and simulations 2024 Ingår i: Nanoscale Horizons. - : Royal Society of Chemistry. - 2055-6756 .- 2055-6764. ; 9:4, s. 506-535 Forskningsöversikt (refereegranskat)
49.	Angizi, S., et al. (författare) A comprehensive review on planar boron nitride nanomaterials: From 2D nanosheets towards 0D quantum dots 2022 Ingår i: Progress in Materials Science. - : Elsevier BV. - 0079-6425. ; 124 Tidskriftsartikel (refereegranskat)abstract Moving from two-dimensional hexagonal boron nitride (2D h-BN) flatlands towards their quantum sized zero-dimensional (0D) islands, as the newest member of the h-BN family, has recently opened up novel research areas due to the emergence of unique optical and physicochemical properties, excellent thermal and chemical stability, and desirable biocompatibility. This review elaborates on the fundamental properties of 2D and 0D h-BN nanomaterials and covers the latest progress in the fabrication and applications of BN nanosheets (BNNSs) and quantum dots (BNQDs). Initially, the transformation of properties in h-BN nanomaterials is discussed when moving from the 2D realm towards the 0D quantum zone. Then, top-down and bottom-up synthesis methods of 2D h-BN are reviewed, analyzing each method's advantages and shortcomings. The review will continue explaining the fabrication methods of BNQDs and the impact of synthesis technique on their physiochemical characteristics. Special attention is given to surface chemistry of BNQD nanocrystals that can alter their electronic band structure and optoelectronic properties. Thereafter, detailed discussion on the implementation of BNNSs and BNQDs in various applications, e.g., catalysts, sensors, bioimaging probes, proton exchange membranes, and photocatalytic activators, is provided. At last, an overview of the ongoing challenges and future directions for BNQD research is presented.
50.	Apelgren, Peter, et al. (författare) Long-term in vivo integrity and safety of3D-bioprinted cartilaginous constructs 2021 Ingår i: Journal of Biomedical Materials Research Part B-Applied Biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 109:1, s. 126-136 Tidskriftsartikel (refereegranskat)abstract Long-term stability and biological safety are crucial for translation of 3D-bioprinting technology into clinical applications. Here, we addressed the long-term safety and stability issues associated with 3D-bioprinted constructs comprising a cellulose scaffold and human cells (chondrocytes and stem cells) over a period of 10 months in nude mice. Our findings showed that increasing unconfined compression strength over time significantly improved the mechanical stability of the cell-containing constructs relative to cell-free scaffolds. Additionally, the cell-free constructs exhibited a mean compressive stress and stiffness (compressive modulus) of 0.04 +/- 0.05 MPa and 0.14 +/- 0.18 MPa, respectively, whereas these values for the cell-containing constructs were 0.11 +/- 0.08 MPa (p= .019) and 0.53 +/- 0.59 MPa (p= .012), respectively. Moreover, histomorphologic analysis revealed that cartilage formed from the cell-containing constructs harbored an abundance of proliferating chondrocytes in clusters, and after 10 months, resembled native cartilage. Furthermore, extension of the experiment over the complete lifecycle of the animal model revealed no signs of ossification, fibrosis, necrosis, or implant-related tumor development in the 3D-bioprinted constructs. These findings confirm the in vivo biological safety and mechanical stability of 3D-bioprinted cartilaginous tissues and support their potential translation into clinical applications.

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