| 1. |
- Colding-Rasmussen, Thomas, et al.
(author)
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Biomechanical Variability and Usability of a Novel Customizable Fracture Fixation Technique
- 2023
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In: Bioengineering. - : MDPI AG. - 2306-5354. ; 10:10
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Journal article (peer-reviewed)abstract
- A novel in situ customizable osteosynthesis technique, Bonevolent™ AdhFix, demonstrates promising biomechanical properties under the expertise of a single trained operator. This study assesses inter- and intra-surgeon biomechanical variability and usability of the AdhFix osteosynthesis platform. Six surgeons conducted ten osteosyntheses on a synthetic bone fracture model after reviewing an instruction manual and completing one supervised osteosynthesis. Samples underwent 4-point bending tests at a quasi-static loading rate, and the maximum bending moment (BM), bending stiffness (BS), and AdhFix cross-sectional area (CSA: mm²) were evaluated. All constructs exhibited a consistent appearance and were suitable for biomechanical testing. The mean BM was 2.64 ± 0.57 Nm, and the mean BS was 4.35 ± 0.44 Nm/mm. Statistically significant differences were observed among the six surgeons in BM (p < 0.001) and BS (p = 0.004). Throughout ten trials, only one surgeon demonstrated a significant improvement in BM (p < 0.025), and another showed a significant improvement in BS (p < 0.01). A larger CSA corresponded to a statistically significantly higher value for BM (p < 0.001) but not for BS (p = 0.594). In conclusion, this study found consistent biomechanical stability both across and within the surgeons included, suggesting that the AdhFix osteosynthesis platform can be learned and applied with minimal training and, therefore, might be a clinically viable fracture fixation technique. The variability in BM and BS observed is not expected to have a clinical impact, but future clinical studies are warranted.
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| 2. |
- Schwarzenberg, Peter, et al.
(author)
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Biomechanical performance of a novel light-curable bone fixation technique
- 2023
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Journal article (peer-reviewed)abstract
- Traumatic bone fractures are often debilitating injuries that may require surgical fixation to ensure sufficient healing. Currently, the most frequently used osteosynthesis materials are metal-based; however, in certain cases, such as complex comminuted osteoporotic fractures, they may not provide the best solution due to their rigid and non-customizable nature. In phalanx fractures in particular, metal plates have been shown to induce joint stiffness and soft tissue adhesions. A new osteosynthesis method using a light curable polymer composite has been developed. This method has demonstrated itself to be a versatile solution that can be shaped by surgeons in situ and has been shown to induce no soft tissue adhesions. In this study, the biomechanical performance of AdhFix was compared to conventional metal plates. The osteosyntheses were tested in seven different groups with varying loading modality (bending and torsion), osteotomy gap size, and fixation type and size in a sheep phalanx model. AdhFix demonstrated statistically higher stiffnesses in torsion (64.64 ± 9.27 and 114.08 ± 20.98 Nmm/° vs. 33.88 ± 3.10 Nmm/°) and in reduced fractures in bending (13.70 ± 2.75 Nm/mm vs. 8.69 ± 1.16 Nmm/°), while the metal plates were stiffer in unreduced fractures (7.44 ± 1.75 Nm/mm vs. 2.70 ± 0.72 Nmm/°). The metal plates withstood equivalent or significantly higher torques in torsion (534.28 ± 25.74 Nmm vs. 614.10 ± 118.44 and 414.82 ± 70.98 Nmm) and significantly higher bending moments (19.51 ± 2.24 and 22.72 ± 2.68 Nm vs. 5.38 ± 0.73 and 1.22 ± 0.30 Nm). This study illustrated that the AdhFix platform is a viable, customizable solution that is comparable to the mechanical properties of traditional metal plates within the range of physiological loading values reported in literature.
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| 3. |
- Ahrenstedt, Lage, et al.
(author)
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Sustained zero-order release of dexamethasone after incorporation into crosslinked PEG-dendrons using click reactions
- 2024
-
In: Journal of Drug Delivery Science and Technology. - : Elsevier BV. - 1773-2247. ; 95
-
Journal article (peer-reviewed)abstract
- Hydrogel-based localised drug delivery minimises systemic side effects and a linear release profile ensuring a sustained drug release over time, crucial for long-term therapy. The current paper describes the use of the Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAc) to append azidified Dexamethasone (Dex) onto dendrons of first- and second-generation PEGs. Crosslinking with thiolated PEGs using either thiol-acrylate or nucleophilic addition reactions yielded gels containing β-thio-ether ester groups that imparted enhanced hydrolytic susceptibility. In vitro gel degradation was followed gravimetrically and expressed as swelling ratios. Thiol-acrylate crosslinked hydrogels exhibited zero-order Dex release kinetics over 11, 27, and 16 days (G1, G1-star, and G2). Crosslinking the G1-gels by nucleophilic addition also resulted in linear release and the end point was reached in 5 days. Hydrolysis was accounted as the main release mechanism for covalently bound Dex, while physically incorporated Dex showed undefined rapid burst or first-order release, with most of the drug released in the initial 1–3 days. Eluates from covalently bound Dex maintained high activity, whereas Trap-Dex gels lost activity over time, as detected by the upregulation of luciferase expression from a transformed cell line. This novel chemistry combination offers precise drug release control applicable beyond Dex to drugs with suitable nucleophilic groups.
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| 4. |
- Andrén, Oliver C. J., et al.
(author)
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Antibiotic-Free Cationic Dendritic Hydrogels as Surgical-Site-Infection-Inhibiting Coatings
- 2019
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In: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659.
-
Journal article (peer-reviewed)abstract
- A non-toxic hydrolytically fast-degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two-component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear-dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2-bis(hydroxymethyl)propionic acid, and ii) a di-N-hydroxysuccinimide functional poly(ethylene glycol) cross-linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged β-alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two-component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G' = 0.5-8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection.
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| 5. |
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| 6. |
- Arseneault, Mathieu, et al.
(author)
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The Dawn of Thiol-Yne Triazine Triones Thermosets as a New Material Platform Suited for Hard Tissue Repair
- 2018
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In: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095. ; 30:52
-
Journal article (peer-reviewed)abstract
- The identification of a unique set of advanced materials that can bear extraordinary loads for use in bone and tooth repair will inevitably unlock unlimited opportunities for clinical use. Herein, the design of high-performance thermosets is reported based on triazine-trione (TATO) monomers using light-initiated thiol-yne coupling (TYC) chemistry as a polymerization strategy. In comparison to traditional thiol-ene coupling (TEC) systems, TYC chemistry has yielded highly dense networks with unprecedented mechanical properties. The most promising system notes 4.6 GPa in flexural modulus and 160 MPa in flexural strength, an increase of 84% in modulus and 191% in strength when compared to the corresponding TATO system based on TEC chemistry. Remarkably, the mechanical properties exceed those of polylactide (PLA) and challenge poly(ether ether ketone) PEEK and today's methacrylate-based dental resin composites. All the materials display excellent biocompatibility, in vitro, and are successfully: i) molded into medical devices for fracture repair, and ii) used as bone adhesive for fracture fixation and as tooth fillers with the outstanding bond strength that outperform methacrylate systems used today in dental restoration application. Collectively, a new era of advanced TYC materials is unfolded that can fulfill the preconditions as bone fixating implants and for tooth restorations.
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| 7. |
- Badria, Adel, et al.
(author)
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Acrylate-free tough 3D printable thiol-ene thermosets and composites for biomedical applications
- 2022
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In: Journal of Applied Polymer Science. - : Wiley. - 0021-8995 .- 1097-4628. ; 139:43
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Journal article (peer-reviewed)abstract
- Polymer thermosets and composites based on rigid trizaine-trione (TATO) alkene and thiol monomers show great promise as bone fixation materials and dental composites due to their ability to efficiently crosslink via thiol-ene coupling chemistry into stiff and strong materials. In order to broaden the scope of these materials, a TATO thermoset was optimized for sterolithography (SLA) 3D printing through the addition of either a diluent (PETMP) and photo-absorber (Sudan I), or the addition of a free radical inhibitor (pyrogallol). A 3D printable hydroxyapatite (HA) composite was also formulated by adding a combination of nano-HA and micro-HA particles, which were found to increase the thermal stability and modulus of the material, respectively. The modulus of the printed thermosets containing Sudan I and pyrogallol exceeded any previously published acrylate-free thiol-ene SLA resins, at 1.6 (0.1) and 1.85 (0.06) GPa, respectively. The printed HA composite formulation had a modulus of 2.4 (0.2) GPa. All three formulations showed a comparable resolution to a commercially available SLA resin and were non-toxic toward Raw 264.7 and human dermal fibroblast cells. These results demonstrate the potential of TATO based SLA resins for the construction of strong, fully-customizable, printed implants for biomedical applications.
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| 8. |
- Biscari, Giuseppina, et al.
(author)
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Gellan gum-dopamine mediated in situ synthesis of silver nanoparticles and development of nano/micro-composite injectable hydrogel with antimicrobial activity
- 2024
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In: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 258
-
Journal article (peer-reviewed)abstract
- Infected skin wounds represent a serious health threat due to the long healing process and the risk of colonization by multi-drug-resistant bacteria. Silver nanoparticles (AgNPs) have shown broad-spectrum antimicrobial activity. This study introduces a novel approach to address the challenge of infected skin wounds by employing gellan gum-dopamine (GG-DA) as a dual-functional agent, serving both as a reducing and capping agent, for the in situ green synthesis of silver nanoparticles. Unlike previous methods, this work utilizes a spray-drying technique to convert the dispersion of GG-DA and AgNPs into microparticles, resulting in nano-into-micro systems (AgNPs@MPs). The microparticles, with an average size of approximately 3 μm, embed AgNPs with a 13 nm average diameter. Furthermore, the study explores the antibacterial efficacy of these AgNPs@MPs directly and in combination with other materials against gram-positive and gram-negative bacteria. The versatility of the antimicrobial material is showcased by incorporating the microparticles into injectable hydrogels. These hydrogels, based on oxidized Xanthan Gum (XGox) and a hyperbranched synthetic polymer (HB10K-G5-alanine), are designed with injectability and self-healing properties through Shiff base formation. The resulting nano-into-micro-into-macro hybrid hydrogel emerges as a promising biomedical solution, highlighting the multifaceted potential of this innovative approach in wound care and infection management.
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| 9. |
- Chang, Tingru, et al.
(author)
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Effect of blue light illumination on atmospheric corrosion and bacterial adhesion on copper
- 2024
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In: Corrosion Science. - : Elsevier BV. - 0010-938X .- 1879-0496. ; 230
-
Journal article (peer-reviewed)abstract
- The effect of blue light on atmospheric corrosion of Cu and on the antimicrobial properties was explored upon exposure mimicking the condition of hygienic surface disinfection. The results show that blue light illumination enhanced the formation of Cu2O, resulting in a slightly increased corrosion resistance of Cu without pre-deposited NaCl, whereas the enhanced formation of Cu2O, CuCl and/or Cu(OH)3Cl on copper with pre-deposited NaCl caused concomitant corrosion product flaking and a reduced corrosion resistance. The blue light induced enhancement of Cu corrosion led to increased surface roughness and more pronounced integration of bacteria within the corrosion products.
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| 10. |
- Cortes Ruiz, Maria F.
(author)
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Tailoring and Characterization of Polymer-linked Fibrillar Structures
- 2024
-
Doctoral thesis (other academic/artistic)abstract
- The development of sustainable and renewable materials is paramount in today’s society. As the most abundant biopolymer on Earth, cellulose from cellulose-rich fibres is an excellent alternative for advanced and innovative material solutions. Nonetheless, competing with the impressive material properties and the low manufacturing costs of fossil-based plastics imposes great challenges. To increase the potential of cellulose fibres in a broader set of applications, the material properties of cellulose need to be tuned depending on the application. An in-depth study of the fibre structure and the application of different tailoring techniques is required to induce tailoring of the physical and chemical properties of the cellulose fibre materials. This thesis focuses on the structure-property relationship of fibrillar hydrogel networks as model structures for the delignified wet-fibre wall. First, a mathematical framework was developed to describe the characteristics of the swelling and mechanical behaviour of anisotropic fibrillar structures, considering the fibril aspect ratio, surface chemistry of the fibrils, and electrolyte concentration in the system. A chemical functionalisation was then introduced to the fibrillar structure, which provided the CNFs with colloidal stability and the ability to participate in free radical polymerisation with monomers and telechelic oligomers. As a result, fibrillar networks were crosslinked with flexible polymer links that provided the network with different mechanical and chemical properties. Additionally, by tailoring the molecular weight of the crosslinks, the ionic strength of the solution, and even the aspect ratio of the fibrils, the mechanical properties of the network were tuned to be either stiffer or more ductile. Finally, an innovative and more sustainable approach was developed to introduce charge and alkene functionality to the fibres. Following the lessons learned from the CNF model investigations, a polymerisation approach was developed in the presence of functionalised fibres. The polymers were grown from the fibre wall, followed by radical crosslinking to create strong Fibre reinforced hydrogel structures. Depending on the application, the method can be easily applied to introduce other types of molecules and functionalities to the fibres and tailor the properties of the fibres to suit a wide range of applications.
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| 11. |
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| 12. |
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| 13. |
- Erlandsson, Johan, et al.
(author)
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On the mechanism behind freezing-induced chemical crosslinking in ice-templated cellulose nanofibril aerogels
- 2018
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In: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 6:40, s. 19371-19380
-
Journal article (peer-reviewed)abstract
- The underlying mechanism related to freezing-induced crosslinking of aldehyde-containing cellulose nanofibrils (CNFs) has been investigated, and the critical parameters behind this process have been identified. The aldehydes introduced by periodate oxidation allows for formation of hemiacetal bonds between the CNFs provided the fibrils are in sufficiently close contact before the water is removed. This is achieved during the freezing process where the cellulose components are initially separated, and the growth of ice crystals forces the CNFs to come into contact in the thin lamellae between the ice crystals. The crosslinked 3-D structure of the CNFs can subsequently be dried under ambient conditions after solvent exchange and still maintain a remarkably low density of 35 kg m-3, i.e. a porosity greater than 98%. A lower critical amount of aldehydes, 0.6 mmol g-1, was found necessary in order to generate a crosslinked 3-D CNF structure of sufficient strength not to collapse during the ambient drying. The chemical stability of the 3-D structure can be further enhanced by converting the hemiacetals to acetals by treatment with an alcohol under acidic conditions.
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| 14. |
- Fan, Yanmiao, et al.
(author)
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Dendritic Hydrogels Induce Immune Modulation in Human Keratinocytes and Effectively Eradicate Bacterial Pathogens
- 2021
-
In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 143:41, s. 17180-17190
-
Journal article (peer-reviewed)abstract
- Infections caused by antibiotic-resistant bacteria are globally a major threat, leading to high mortality rates and increased economic burden. Novel treatment strategies are therefore urgently needed by healthcare providers to protect people. Biomaterials that have inherent antibacterial properties and do not require the use of antibiotics present an attractive and feasible avenue to achieve this goal. Herein, we demonstrate the effect of a new class of cationic hydrogels based on amino-functional hyperbranched dendritic-linear-dendritic copolymers (HBDLDs) exhibiting excellent antimicrobial activity toward a wide range of clinical Gram-positive and Gram-negative bacteria, including drug-resistant strains isolated from wounds. Intriguingly, the hydrogels can induce the expression of the antimicrobial peptides RNase 7 and psoriasin, promoting host-mediated bacterial killing in human keratinocytes (HaCaT). Moreover, treatment with the hydrogels decreased the proinflammatory cytokine IL-1 beta, reactive nitrogen species (NO), and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells, conjunctively resulting in reduced inflammation.
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| 15. |
- Fan, Yanmiao, et al.
(author)
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Nanogel encapsulated hydrogels as advanced wound dressings for the controlled delivery of antibiotics
- 2021
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In: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 31
-
Journal article (peer-reviewed)abstract
- Biocompatible and degradable dual-delivery gel systems based on hyperbrancheddendritic−linear−dendritic copolymers (HBDLDs) is herein conceptualizedand accomplished via thiol-ene click chemistry. The elasticity of thehydrogels is tunable by varying the lengths of PEG (2, 6, 10 kDa) or the dryweight percentages (20, 30, 40 wt%), and are found to be between 2–14.7 kPa,comparable to human skin. The co-delivery of antibiotics is achieved, wherethe hydrophilic drug novobiocin sodium salt (NB) is entrapped within thehydrophilic hydrogel, while the hydrophobic antibiotic ciprofloxacin (CIP) isencapsulated within the dendritic nanogels (DNGs) with hydrophobic cores(DNGs-CIP). The DNGs-CIP with drug loading capacity of 2.83 wt% are thenphysically entrapped within the hybrid hydrogels through UV curing. Thehybrid hydrogels enabled the quick release of NB and prolonged released ofCIP. In vitro cell infection assays showed that the antibiotic-loaded hybridhydrogels are able to treat bacterial infections with significant bacterialreduction. Hybrid hydrogel band aids are fabricated and exhibited betterantibacterial activity compared with commercial antimicrobial band aids.Remarkably, most hydrogels and hybrid hydrogels showed enhanced humandermal cell proliferation and could be degraded into non-toxic constituents,showing great promise as wound dressing materials.
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| 16. |
- Fan, Yanmiao, et al.
(author)
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Placenta Powder-Infused Thiol-Ene PEG Hydrogels as Potential Tissue Engineering Scaffolds
- 2023
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In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 24:4, s. 1617-1626
-
Journal article (peer-reviewed)abstract
- Human placenta is a source of extracellular matrix for tissue engineering. In this study, placenta powder (PP), made from decellularized human placenta, was physically incorporated into synthetic poly(ethylene glycol) (PEG)-based hydrogels via UV-initiated thiol-ene coupling (TEC). The PP-incorporated PEG hydrogels (MoDPEG+) showed tunable storage moduli ranging from 1080 ± 290 to 51,400 ± 200 Pa. The addition of PP (1, 4, or 8 wt %) within the PEG hydrogels increased the storage moduli, with the 8 wt % PP hydrogels showing the highest storage moduli. PP reduced the swelling ratios compared with the pristine hydrogels (MoDPEG). All hydrogels showed good biocompatibility in vitro toward human skin cells and murine macrophages, with cell viability above 91%. Importantly, cells could adhere and proliferate on MoDPEG+ hydrogels due to the bioactive PP, while MoDPEG hydrogels were bio-inert as cells moved away from the hydrogel or were distributed in a large cluster on the hydrogel surface. To showcase their potential use in application-driven research, the MoDPEG+ hydrogels were straightforwardly (i) 3D printed using the SLA technique and (ii) produced via high-energy visible light (HEV-TEC) to populate damaged soft-tissue or bone cavities. Taking advantage of the bioactivity of PP and the tunable physicochemical properties of the synthetic PEG hydrogels, the presented MoDPEG+ hydrogels show great promise for tissue regeneration.
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| 17. |
- Fan, Yanmiao, et al.
(author)
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Scalable Dendritic Hydrogels Targeting Drug-Resistant Skin Pathogens and the Immunomodulation Activity in Keratinocytes
-
Other publication (other academic/artistic)abstract
- Microbial infections caused by antibiotic-resistant bacteria are a major threat to humans, associated with a high mortality and for the society increased economic burden. To address this, a series of cationic hydrogels based on amino-functional hyperbranched dendritic−linear−dendritic copolymers (HBDLDs) were formed easily within 1 min through interactions between the amino-terminated HBDLDs and di(N-hydroxysuccinimide ester) functionalized polyethylene glycol (PEG). The hydrogels exhibited excellent inherent antimicrobial activity towards a wide range of Gram-positive and Gram-negative clinical bacteria including drug-resistant strains, isolated from wounds. In vitro cell infection assays showed that the hydrogels were able to significantly reduce cell infections caused by different strains, with the highest killing efficacy of 96% towards S. aureus. The hydrogels also inhibited the initiation of E. coli biofilm formation. Remarkably, the hydrogels induced the expression of the antimicrobial peptides, RNase 7 and psoriasin, in keratinocytes (HaCaT) which suggests that the hydrogels are likely able to promote host-mediated bacterial killing. The expression of pro-inflammatory cytokine IL-1β, reactive nitrogen species (NO) and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells were reduced after the treatment with the hydrogels. The hydrogels degraded within 24 h, showing great promise for treating skin infections and reducing inflammation.
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| 18. |
- Fan, Yanmiao, et al.
(author)
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Self-Assembled Polyester Dendrimer/Cellulose Nanofibril Hydrogels with Extraordinary Antibacterial Activity
- 2020
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In: Pharmaceutics. - : MDPI. - 1999-4923. ; 12:12
-
Journal article (peer-reviewed)abstract
- Cationic dendrimers are intriguing materials that can be used as antibacterial materials; however, they display significant cytotoxicity towards diverse cell lines at high generations or high doses, which limits their applications in biomedical fields. In order to decrease the cytotoxicity, a series of biocompatible hybrid hydrogels based on cationic dendrimers and carboxylated cellulose nanofibrils were easily synthesized by non-covalent self-assembly under physiological conditions without external stimuli. The cationic dendrimers from generation 2 (G2) to generation 4 (G4) based on trimethylolpronane (TMP) and 2,2-bis (methylol)propionic acid (bis-MPA) were synthesized through fluoride promoted esterification chemistry (FPE chemistry). FTIR was used to show the presence of the cationic dendrimers within the hybrid hydrogels, and the distribution of the cationic dendrimers was even verified using elemental analysis of nitrogen content. The hybrid hydrogels formed from G3 and G4 showed 100% killing efficiency towards Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) with bacterial concentrations ranging from 10(5) CFU/mL to 10(7) CFU/mL. Remarkably, the hybrid hydrogels also showed good biocompatibility most probably due to the incorporation of the biocompatible CNFs that slowed down the release of the cationic dendrimers from the hybrid hydrogels, hence showing great promise as an antibacterial material for biomedical applications.
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| 19. |
- Fan, Yanmiao
(author)
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The synthesis of dendritic hydrogels and inorganic nanoparticles and their application as antibacterial and imaging materials
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- AbstractThe overuse and misuse of conventional antibiotics has caused increased prevalence of drug-resistant bacteria, the infections of which cause high mortality and economic losses per year. It is therefore crucial to develop new technologies and treatments for infections caused by drug-resistant bacteria. Dendritic polymer-based hydrogels and nanomaterials have shown promise as alternatives to traditional small-molecule antibiotics.Third generation (G3) allyl-functional hyperbranched dendritic-linear-dendritic copolymers (HBDLDs) based on polyethylene glycol (PEG) and 2,2-bis(hydroxymethyl) propionic acid (bis-MPA) were synthesized, and used to form hydrogels with a dithiol-functional PEG crosslinker using thiol-ene coupling (TEC). The hydrogels were used to co-deliver both hydrophilic and hydrophobic antibiotics with the aid of dendritic nanogels (DNGs). Antibacterial hydrogel band aids were also fabricated in a facile procedure.Amino-functional HBDLDs based on PEG and bis-MPA were synthesized, and together with a di-N-hydroxysuccinimide-functional PEG as the crosslinker, amino-functional hydrogels with inherent antibacterial properties were fabricated. The cationic hydrogels are highly effective towards a wide range of wound-isolated bacteria, and can reduce inflammation and oxidative stress.To minimize the cytotoxicity of amino-functional dendrimers, self-assembled hydrogels based on cationic dendrimers and cellulose nanofibrils were fabricated. Cationic dendrimers and their fragments can be released from the hydrogels to kill bacteria whilst showing insignificant cytotoxicity with human cells.Bis-MPA dendrimers with both amino and allyl functionalities were also synthesized. Allyl groups can be used to form hydrogels with a dithiol-functional PEG crosslinker via TEC, and the amino groups provide the hydrogels with antibacterial properties.Fluorescent silicon nanoparticles (SiNPs) were synthesized and their interaction with bacteria was investigated. SiNPs exhibited strong binding to Staphylococcus aureus (S. aureus), showing promise as a potential capturing and imaging agent for S. aureus.
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| 20. |
- Garcia Gallego, Sandra, et al.
(author)
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Accelerated Chemoselective Reactions to Sequence-Controlled Heterolayered Dendrimers
- 2020
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In: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126.
-
Journal article (peer-reviewed)abstract
- Chemoselective reactions are a highly desirable approach to generate well-defined functional macromolecules. Their extraordinary efficiency and selectivity enable the development of flawless structures, such as dendrimers, with unprecedented structure-to-property capacity but with typically tedious synthetic protocols. Here we demonstrate the potency of chemoselective reactions to accomplish sequence-controlled heterolayered dendrimers. An accurate accelerated design of bis-MPA monomers with orthogonally complementary moieties and a wisely selected chemical toolbox generated highly complex monodisperse dendrimers through simplified protocols. The versatility of the strategy was proved by obtaining different dendritic families with different properties after altering the order of addition of the monomers. Moreover, we evaluated the feasibility of the one-pot approach toward these heterolayered dendrimers as proof-of-concept.
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| 21. |
- Garcia-Gallego, Sandra, et al.
(author)
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Synthesis of Heterofunctional Polyester Dendrimers with Internal and External Functionalities as Versatile Multipurpose Platforms
- 2020
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In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 21:10, s. 4273-4279
-
Journal article (peer-reviewed)abstract
- Heterofunctional dendrimers with internal and external representations of functionalities are considered as the ultimate dendritic frameworks. This is reflected by their unprecedented scaffolding, such as precise control over the structure, molecular weight, number, and location of different cargos across the whole dendritic skeleton. Consequently, these dendrimers with multipurpose characters are the pinnacle of precision polymers and thereof are highly attractive to the scientific community as they can find use in a great number of cutting-edge applications, especially as discrete unimolecular carriers for therapeutic exploitation. Unfortunately, most established dendrimer families display external functionalities but lack internal scaffolding ability, which leads to inherent limitations to their full potential use as precision carriers. Consequently, here, we embark on a novel synthetic strategy facilitating the introduction of internal functionalization of established dendrimers. As a proof of concept, a new class of internally and externally functionalized multipurpose dendrimers based on the established 2,2-bis(methylol)propionic acid (bis-MPA) was successfully obtained by the elegant and simple design of AB2C monomers, amalgamated from two traditional AB2 monomers. Utilizing fluoride-promoted esterification (FPE), straightforward layer-by-layer divergent growth up to the fourth generation was successful in less than one day of reaction time, with a molecular weight of 15 kDa, and displaying 93 reactive groups divided by 45 internal and 48 external functionalities. The feasibility of postfunctionalization through click reactions is demonstrated, where the fast and effective attachment of drugs, dyes, and PEG chains is achieved, as well as cross-linking into multifunctional hydrogels. The simplicity and versatility of the presented strategy can easily be transferred to generate a myriad of functional materials such as polymers, surfaces, nanoparticles, or biomolecules.
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| 22. |
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| 23. |
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| 24. |
- He, Guiying, et al.
(author)
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Promoting multiexciton interactions in singlet fission and triplet fusion upconversion dendrimers
- 2023
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Journal article (peer-reviewed)abstract
- Singlet fission and triplet-triplet annihilation upconversion are two multiexciton processes intimately related to the dynamic interaction between one high-lying energy singlet and two low-lying energy triplet excitons. Here, we introduce a series of dendritic macromolecules that serve as platform to study the effect of interchromophore interactions on the dynamics of multiexciton generation and decay as a function of dendrimer generation. The dendrimers (generations 1–4) consist of trimethylolpropane core and 2,2-bis(methylol)propionic acid (bis-MPA) dendrons that provide exponential growth of the branches, leading to a corona decorated with pentacenes for SF or anthracenes for TTA-UC. The findings reveal a trend where a few highly ordered sites emerge as the dendrimer generation grows, dominating the multiexciton dynamics, as deduced from optical spectra, and transient absorption spectroscopy. While the dendritic structures enhance TTA-UC at low annihilator concentrations in the largest dendrimers, the paired chromophore interactions induce a broadened and red-shifted excimer emission. In SF dendrimers of higher generations, the triplet dynamics become increasingly dominated by pairwise sites exhibiting strong coupling (Type II), which can be readily distinguished from sites with weaker coupling (Type I) by their spectral dynamics and decay kinetics.
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| 25. |
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| 26. |
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| 27. |
- Hern, Faye Y., et al.
(author)
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Model studies of the sequential and simultaneous statistical modification of dendritic functional groups and their implications within complex polymer architecture synthesis
- 2017
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In: Polymer Chemistry. - : Royal Society of Chemistry. - 1759-9954 .- 1759-9962. ; 8:10, s. 1644-1653
-
Journal article (peer-reviewed)abstract
- Post-synthesis modification of polymers is a synthetically appealing approach to generate a range of samples from a single, well-characterised starting material. When partial or mixed-functionalisation is sought, an inevitable statistical distribution of modification outcomes will lead to considerable variation of chemical structures within the final sample. Here we have comprehensively investigated the postsynthesis sequential/partial and simultaneous mixed modification of xanthate-functional ideal dendrons and used this data to consider the implications for the more complex linear-dendritic hybrids and hyper-branched- polydendron analogues. Although H-1 NMR confirmed the potential to direct the reactions, it was clear from MALDI-TOF studies that very little of the actual targeted structures were generated in the statistical reactions.
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| 28. |
- Hult, Anders, et al.
(author)
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Dendrimers with interior and exterior functionalities comprising of azide or alkyne groups for post- functionalization by huisgen click cycloaddition
- 2008
-
Patent (pop. science, debate, etc.)abstract
- Novelty: A dendritic polymer comprising a core and repeating units, is new. Every repeating unit is bound to other unit(s) with bond(s) consisting of an ester, amide, thioether, ether, urethane, amine or imine.Use: The dendritic polymer is used for drug delivery systems, tissue engineering, data storage devices, markers for imaging, diagnostics, vaccines, phototherapeutics, optical devices, semiconductor, bioactive hydrogels and/or catalysts; for manufacture of a particle and a hydrogel (claimed); and for coatings, polyfunctional initiators for controlled radical polymerization or living free-radical polymerization techniques, ring-opening metathesis polymerization and ring-opening polymerization, dental and other composite materials, additives to control viscosity, rheology, solubility and stabilizing capacity, hybrid organic-inorganic materials, water-soluble materials, amphiphilic architectures, well-defined building blocks for precise architectural control, deposition of dendrimers on solid surfaces, dispersing agents for nanoparticles, dendrimer vehicles for encapsulation and/or delivery, and dendrimer scaffolds. The particle is used in encapsulation of low molecular compounds such as potent drugs, chelating species and fluorescent dyes.Advantage: The dendritic polymer can be functionalized both in the interior and in the exterior. It is possible to use a one-pot growth of dendritic polymer. There is provided the possibility to have more functional groups in a dendritic polymer compared to conventional polymer. When comparing the number of functional groups of a dendrimer based on A'B' x C' y -monomers with a traditional dendrimer based A'B' x -monomers, it is evident that the intrinsic functionality provides a larger number of available functional groups for post-modification. There is provided the possibility of a synthesis which is very robust, can be performed in various solvents, performed at both ambient and elevated temperatures, performed at atmospheric pressure as well as elevated, performed in a variety of gases including oxygen, nitrogen or argon. The synthesis has a high yield making the manufacture economical. There is the possibility to exclude an activation step prior to post-functionalization of a dendritic polymer. There is provided the possibility to add different types of functional groups simultaneously both to inner layer and/or to the outer layer.
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| 29. |
- Hult, Daniel, 1986-, et al.
(author)
-
Degradable High Tg Sugar Derived Polycarbonates from Isosorbide and Dihydroxyacetone
- 2018
-
In: Polymer Chemistry. - : Royal Society of Chemistry. - 1759-9954 .- 1759-9962. ; 9:17, s. 2238-2246
-
Journal article (peer-reviewed)abstract
- Polycarbonates from isosorbide and dihydroxyacetone (DHA) have been synthesised using organocatalytic step-growth polymerization of their corresponding diols and bis-carbonylimidazolides monomers. By choice of feed ratio and monomer activation, either isosorbide or ketal protected DHA, random and alternating poly(Iso-co-DHA) carbonates have been formed. Thermal properties by DSC and TGA were herein strongly correlated to monomer composition. Dilution studies using 1H-NMR of a model compound DHA-diethyl carbonate in acetonitrile and deuterated water highlighted the influence of α-substituents on the keto/hydrate equilibrium of DHA. Further kinetics studies of in the pH* range of 4.7 to 9.6 serve to show the hydrolytic pH-profile of DHA-carbonates. The Hydrolytic degradation of deprotected polymer pellets show an increased degradation with increasing DHA content. Pellets with a random or alternating configuration show different characteristics in terms of mass loss and molecular weight loss profile over time.
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| 30. |
- Hult, Daniel, 1986-
(author)
-
Versatile Synthetic Strategies to Highly Functional Polyesters and Polycarbonates
- 2018
-
Doctoral thesis (other academic/artistic)abstract
- Polymers have become ubiquitous in today’s society and are found in everything from household items to airplanes and automobiles. Synthetic polymeric materials are as diverse as their applications and their final properties are highly reliant on the building blocks and methods used to assemble them. In the field of biomedical materials, polyesters and polycarbonates have been hailed as excellent materials in large part due to their inherent hydrolytic degradability. With this in mind, careful choice of monomers can ensure that materials not only conform to the desired physical properties, but also elicit a favorable biological response. The utilization of post-polymerization modification of these promising materials has the capability of opening up further avenues to target even more advanced applications. Unfortunately, rigorous and difficult reaction conditions, including multi-step synthesis have to a certain extent held back the adoption of these complex functional materials in applied research. In a pragmatic approach, a sustainable framework was developed in this thesis to seek out more practical methods, limiting the amount of reaction steps and overtly hazardous chemicals.In a first study, we set out to simplify and scale-up the synthesis of cyclic carbonates with pendant functional groups, capable of undergoing controlled ring-opening polymerization. By avoiding the use of protective-group chemistry we were able two devise a two-step method to create a library of functional monomers. Results in this study show that reactive intermediates could be isolated on 100 g scales, which in a second step was functionalized with a desired alcohol.With this framework in mind, key practical decisions were made to drastically re-think the work up procedures for greater scalability of bis-MPA dendrimers. In this work, a more efficient, scalable and sustainable approach was devised. Elimination of traditional arduous purification steps led to the synthesis of monodisperse dendrimers up to the sixth generation, with 192 functional groups on 50 g scales. Further work included the omission of protective group-chemistry, using orthogonal functional groups to cut the number of synthetic steps by half.The know-how developed in the first two projects led us to pursue greater scalability of functional polycarbonates through a simpler polymerization technique. The method allowed the step-growth polymerization of functional materials from more easily accessible monomers isolated on 100 g scales. Subsequent polymerization afforded materials with glass transition temperatures in the range of -45 °C to 169 °C. The method served as a complement to cyclic carbonates, offering a wider range of functional monomers. Furthermore, by careful choice of assembly method, both alternating and scrambled compositions could be achieved.In a final study, we set out to take advantage of the scrambling mechanism. Control of the final composition of highly rigid degradable polycarbonates was pursued, using renewable building-blocks derived from sugar. In a proof of concept study, thermal and hydrolytic stability of these materials is shown to be dependent on both amount and configuration of each monomer in the final material.
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| 31. |
- Hutchinson, Daniel, et al.
(author)
-
Highly Customizable Bone Fracture Fixation through the Marriage of Composites and Screws
- 2021
-
In: Advanced Functional Materials. - : John Wiley and Sons Inc. - 1616-301X .- 1616-3028. ; 31:41
-
Journal article (peer-reviewed)abstract
- Open reduction internal fixation (ORIF) metal plates provide exceptional support for unstable bone fractures; however, they often result in debilitating soft-tissue adhesions and their rigid shape cannot be easily customized by surgeons. In this work, a surgically feasible ORIF methodology, called AdhFix, is developed by combining screws with polymer/hydroxyapatite composites, which are applied and shaped in situ before being rapidly cured on demand via high-energy visible-light-induced thiol–ene coupling chemistry. The method is developed on porcine metacarpals with transverse and multifragmented fractures, resulting in strong and stable fixations with a bending rigidity of 0.28 (0.03) N m2 and a maximum load before break of 220 (15) N. Evaluations on human cadaver hands with proximal phalanx fractures show that AdhFix withstands the forces from finger flexing exercises, while short- and long-term in vivo rat femur fracture models show that AdhFix successfully supports bone healing without degradation, adverse effects, or soft-tissue adhesions. This procedure represents a radical new approach to fracture fixation, which grants surgeons unparalleled customizability and does not result in soft-tissue adhesions. © 2021 The Authors.
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| 32. |
- Ingverud, Tobias, et al.
(author)
-
Dendritic Polyampholyte-Assisted Formation of Functional Cellulose Nanofibril Materials
- 2020
-
In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 21:7, s. 2856-2863
-
Journal article (peer-reviewed)abstract
- A new platform of functional hybrid materials from anionically charged high-aspect-ratio cellulose nanofibrils (CNFs) and a dendritic polyampholyte, Helux, is herein proposed. The polyampholytic character of Helux enabled facile and efficient nanoscale mixing with the CNFs, and the resulting composite mixtures of CNFs and Helux displayed thixotropic behavior and formed physical and reversibly cross-linked gels when left unperturbed for short spans of time. The gel could be chemically cross-linked into self-supporting solid hydrogels containing impressive water contents of 99.6% and a storage modulus of 1.8 kPa by thermal activation. Non-cross-linked mixtures of CNF/Helux were assembled into composites, such as films by solvent casting and aerogels with densities as low as 4 kg/m(3) by lyophilizing ice-templated CNF/Helux mixtures. The resulting materials exhibited excellent wet stability due to the heat-activated cross-linking and were readily available for postfunctionalization via amidation chemistry using Helux-accessible amines in aqueous conditions. The mechanical performance of the films was not jeopardized by the addition of Helux. Additionally, by varying the amount of Helux, the compressive elastic modulus of aerogels was tunable in both the non-cross-linked and cross-linked states. The fast and efficient nanoscale mixing of anionic CNFs and a polymer containing cationic groups is unique, novel, and promising as a functional material platform. Sustainable CNFs guided by heterofunctional dendritic polyampholytes are envisaged to act as a pillar toward high-performance applications, including biomedicine and biomaterials.
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| 33. |
- Ingverud, Tobias, et al.
(author)
-
Helux : A Heterofunctional Hyperbranched Poly(amido amine) Carboxylate
- 2019
-
In: ACS APPLIED POLYMER MATERIALS. - : AMER CHEMICAL SOC. - 2637-6105. ; 1:7, s. 1845-1853
-
Journal article (peer-reviewed)abstract
- Herein we present the first scientific report on the commercially available Helux 33/16 - a heterofunctional poly(amido amine carboxylate) hyperbranched polymer (Native Helux). The Native Helux, built from diethyl maleate (DEM) and diaminohexane (HMDA), was characterized, in part aided by reverse engineering of a similar scaffold with the same monomers. Different purification methods resulted in higher molecular weight polymers ranging from 8.4 to 51.7 kDa (M-w), and the Helux considered the purest, having 10 mmol (primary and secondary amines)/g as well as 2-4 mmol carboxylic/g Helux. Additionally, aqueous-mediated postmodifications of Helux were achieved including Michael addition, guanylation, and ring-opening of sultone, as well as water/ethyl acetate-mediated amidation of imidazole-activated pentenoic acid. The inherent heterofunctionality of Helux, amines and carboxylic groups, was further explored by a one-component self-cross-linking approach that yielded a dendritic poly(amido amine) network with autofluorescence-exhibiting properties and a T-g of 59 degrees C. The Helux network exhibited a storage modulus (G') of 7.9 MPa at 25 degrees C and in dry state, and 0.9 MPa (G') when plasticized by 50 wt % swelling (in water) of the network. Finally, dendritic hydrogels based on Helux were produced by a spontaneous NHS-amidation reaction with difunctional 10kPEG-NHS. The mechanical properties of the hydrogels were found to be dependent on the curing temperature for the hydrogel, yielding a G' of 8 and 14.5 kPa, a stress at break of 11.5 and 22.7 kPa, and a strain-at-break of 161 and 163%, at 25 and 37 degrees C, respectively.
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| 34. |
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| 35. |
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| 36. |
- Kikionis, Stefanos, et al.
(author)
-
Nanofibrous nonwovens based on dendritic-linear-dendritic poly(ethylene glycol) hybrids
- 2018
-
In: Journal of Applied Polymer Science. - : John Wiley & Sons. - 0021-8995 .- 1097-4628. ; 135:10
-
Journal article (peer-reviewed)abstract
- Dendritic-linear-dendritic (DLD) hybrids are highly functional materials combining the properties of linear and dendritic polymers. Attempts to electrospin DLD polymers composed of hyperbranched dendritic blocks of 2,2-bis(hydroxymethyl) propionic acid on a linear poly(ethylene glycol) core proved unsuccessful. Nevertheless, when these DLD hybrids were blended with an array of different biodegradable polymers as entanglement enhancers, nanofibrous nonwovens were successfully prepared by electrospinning. The pseudogeneration degree of the DLDs, the nature of the co-electrospun polymer and the solvent systems used for the preparation of the electrospinning solutions exerted a significant effect on the diameter and morphology of the electrospun fibers. It is worth-noting that aqueous solutions of the DLD polymers and only 1% (w/v) poly(ethylene oxide) resulted in the production of smoother and thinner nanofibers. Such dendritic nanofibrous scaffolds can be promising materials for biomedical applications due to their bio-compatibility, biodegradability, multifunctionality, and advanced structural architecture.
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| 37. |
- Latorre-Sanchez, Alejandro, et al.
(author)
-
Active quinine-based films able to release antimicrobial compounds via melt quaternization at low temperature
- 2018
-
In: Journal of materials chemistry. B. - : ROYAL SOC CHEMISTRY. - 2050-750X .- 2050-7518. ; 6:1, s. 98-104
-
Journal article (peer-reviewed)abstract
- The fabrication of antibacterial films based on renewable materials (e.g., chitosan) has attracted significant interest in fields such as food packaging, health care and medicine. However, exploiting the antibacterial properties of cinchona alkaloids to design active nanostructured films able to release quinine-based antimicrobial compounds has not been considered previously. Herein, we develop two different routes to produce active quinine-based nanostructured cross-linked films by exploiting the multiple reactive sites of quinine and, specifically, both the nitrogen atom and the vinyl group of the quinuclidine portion of the molecule, as well as their corresponding orthogonal quaternization and thiol-ene coupling reactions. The first synthetic strategy produces stiff and brittle nanostructured quinine-based films of limited utility for practical applications. Conversely, the second approach produces active, flexible and nanostructured quinine-based films (T-g = - 14 degrees C, Young's modulus = 1.3 GPa), which are able to release antimicrobial compounds against E. coli that, remarkably, are noncytotoxic against mouse macrophage and human dermal fibroblast cells. These kinds of active cinchona alkaloid-based coatings are easy to prepare by means of simple, solvent-free, melt quaternization/spreading procedures at a relatively low temperature (120 degrees C), making this second approach one of the most facile reported procedures to date to produce active nanostructured bio-based films.
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| 38. |
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| 39. |
- Lin, Jinjian, et al.
(author)
-
Impact of Polyester Dendrimers as Branched Multifunctional Cross-Linking Additives in Triazine-Trione-Based Composites Developed via High-Energy Visible Light Thiol-ene Chemistry
- 2023
-
In: ACS APPLIED POLYMER MATERIALS. - : American Chemical Society (ACS). - 2637-6105. ; 5:12, s. 10395-10403
-
Journal article (peer-reviewed)abstract
- Hydroxyapatite (HA) infused triazine-trione (TATO) composites have emerged as an injectable platform for customizable bone fixators due to their fast and benign curing via high-energy visible light-induced thiol-ene chemistry (HEV-TEC), promising mechanical performance, and preclinical outcomes. These composites can overcome many of the existing limitations accompanying metal implants such as poor patient customizability, soft tissue adhesions, and stress shielding. Taking into account that the promising benchmarked TATO composite (BC) is based on stable sulfur-carbon bonds, we herein investigate the impact of introducing polyester dendritic cross-linkers based on bis-MPA as chemically integrated branched additives that display labile esters in a branched configuration. The inclusion of dendrimers, G1 and G3, in concentrations of 1, 3, and 5 wt % in the composite formulations were found to (i) decrease the processing viscosity of the composite formulations, reaching Newtonic and nonshear thinning behavior at 37 degree celsius and (ii) impact the size distribution of bubble cavities in the composite cross sections. The lowest collected T-g for the dendrimer-containing composites was noted to be 73.2 degree celsius, a temperature well above physiological temperature. Additionally, all composites displayed flexural modulus above 6 GPa and flexural strength of ca. 50 MPa under dry conditions. The composites comprising 5 wt % of G1 and G3 dendrimers, with ester bond densities of 0.208 and 0.297 mmol/g, respectively, reached a mass loss up to 0.27% in phosphate buffered saline at 37 degree celsius, which is within the range of established polycaprolactone (PCL). Combined with the nontoxic properties extracted from the cell viability study, polyester dendrimers were determined as promising additives which compatibilized well with the TATO formulation and cross-linked efficiently resulting in strong composites suited for bone fracture fixations.
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| 40. |
- Lin, Jinjian, et al.
(author)
-
Soft Hydroxyapatite Composites Based on Triazine-Trione Systems as Potential Biomedical Engineering Frameworks
- 2023
-
In: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 15:5, s. 7329-7339
-
Journal article (peer-reviewed)abstract
- Composites of triazine-trione (TATO) thiol-ene networks and hydroxyapatite (HA) have shown great potential as topological fixation materials for complex bone fractures due to their high flexural modulus, biocompatibility, and insusceptibility to forming soft-tissue adhesions. However, the rigid mechanical properties of these composites make them unsuitable for applications requiring softness. The scope of these materials could therefore be widened by the design of new TATO monomers that would lead to composites with a range of mechanical properties. In this work, four novel TATO-based monomers, decorated with either ester or amide linkages as well as alkene or alkyne end groups, have been proposed and synthesized via fluoride-promoted esterification (FPE) chemistry. The ester-modified monomers were then successfully formulated along with the thiol TATO monomer tris [2-(3-mercaptopropionyloxy)ethyl] isocyanurate (TEMPIC) and HA to give soft composites, following the established photo-initiated thiol-ene coupling (TEC) or thiol-yne coupling (TYC) chemistry methodologies. The most promising composite shows excellent softness, with a flexural modulus of 57 (2) MPa and ϵf at maximum σf of 11.8 (0.3)%, which are 117 and 10 times softer than the previously developed system containing the commercially available tri-allyl TATO monomer (TATATO). Meanwhile, the surgically convenient viscosity of the composite resins and their excellent cytotoxicity profile allow them to be used in the construction of soft objects in a variety of shapes through drop-casting suitable for biomedical applications.
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| 41. |
- Lin, Jinjian, 1995-
(author)
-
Synthesis and characterization of “Clickable” triazine-trione based thermosets and composites via Thiol-Ene and Thiol-Yne Photochemistry
- 2024
-
Doctoral thesis (other academic/artistic)abstract
- Triazine trione (TATO)-based thiol-ene and thiol-yne (TEC and TYC) thermosets and hydroxyapatite (HA) composites have proven their potential as bone fracture fixation implants for use in open reduction internal fixation (ORIF), a field which is currently dominated by metal implants which usually require a second operation for removal. These composites demonstrate high flexural modulus and strength as well as excellent biocompatibility. As injectable implants they are well-aligned with the surgeons needs for more patient-customized solutions to treat bone fractures. While promising, the non-degradable properties of current systems hinder their full potential to fully resorbable implants after complete bone healing. Hence, the foundation of this thesis was to expand the family of TATO thermosets and composites targeting key requirements on future biomaterials suited for bone tissue regeneration. Two different approaches were adopted in this thesis, namely the formulation of composites based on newly synthesized TATO-based monomers, and infusing polyester dendrimers into the existing TATO-HA formulation. The rationale behind both approaches was that the introduction of hydrolysable groups, from either the new TATO monomers or the dendrimers, would increase degradation but also impact the mechanical properties of the composite. The potential clinical applications of these new formulations were investigated through the evaluation of their mechanical, processability, biocompatibility and degradation properties.In the first approach, TATO-based alkene and alkyne monomers, containing either ester or amide linkages, were synthesized via fluoride promoted esterification (FPE) chemistry. Thermosets and composites were formulated with the resulting triester TATO monomers (TESTATO), commercially available triester TATO thiol (TEMPIC) and biocompatible hydroxyapatite (HA) filler. These formulations generated photo-initiated TEC and TYC crosslinked composites containing hydrolysable ester groups. These ester-rich materials displayed soft and flexible properties, differing from the previouspreviously formulated rigid and strong TATO-based composites. Cytotoxicity testing showed the new composites did not negatively affect cell viability. The high customizability of the TESTATO based composites was demonstrated through the drop-casting of objects such as rings, rods, tubes, and thin films (Paper I). These soft and flexibility composites were not suitable for bone fixation; however, they were investigated for their applications as tissue engineering (TE) scaffolds (Paper III) and anti-soft tissue adhesion coatings on metal implants (Paper IV). In the work of Paper III, numerous characterizations were applied to study the potential of the TESTATO based thermosets as tissue-engineering scaffolds, including mechanical testing, surface analysis, enzymatic degradation testing, and biocompatibility with bone marrow mesenchymal stromal cells (BMSCs). Collected results suggested that these ester-rich TEC and TYC thermoset materials showcased competitive properties to medical grade PCL, especially in the sense of biocompatibility and flexibility. Meanwhile, their convenient viscosity and ability to be cured on demand with light-initiated TEC and TYC chemistry allowed them to be fabricated into TE devices using different methodologies including drop-casting, salting leaching, thin filming and 3D printing. Moreover, the merits of flexibility and high processability of TESTATO based HA composites were applied to create flexible anti-soft tissue adhesion coatings on metal implants (Paper IV). Initial studies demonstrated that these soft TATO-HA composite coated metal plates were hydrophilic and able to withstand flexural displacement of 2 mm, under both dry and wet conditions, which is advantageous for potential future in vivo studies.In the second approach, polyester dendrimers with 1 and 3 generations were successfully integrated into the previously established rigid and strong TATO-HA composites in small weight percentages via HEV light-initiated TEC reactions. The addition of the dendrimers did not negatively affect the composites’ flexural modulus and strength under both dry and wet conditions. Moreover, the addition of these dendrimers was found to impact the viscosity of the resins of all formulations and reduce the size distribution of trapped bubbles in the composite cross sections.Both approaches aimed at introducing hydrolysable linkages into the TATO based systems. The inclusion of the G1 dendrimer significantly improved degradation while the TESTATO-alkene based composite showed the best hydrolytic degradation. However, the improvements to the degradation kinetics were more modest than expected, demonstrating that additional work, such using fillers that are more degradable than HA, will be required in the future.
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| 42. |
- Liu, Hua, et al.
(author)
-
Advance in oral delivery of living material
- 2023
-
In: Biomedical Technology. - : Elsevier BV. - 2949-723X. ; 3, s. 26-39
-
Research review (peer-reviewed)abstract
- Nowadays, living therapeutics is a promising candidate among various therapies, and oral administration of living therapeutics characterized by universality and safety avail to make the transition from bench to bedside. However, precise delivery and continuous maintenance of cell viability and activity to acquire stable and ideal therapeutic efficacy remain challenging. Living material is the smart integration of the flexibly programmable functionality of biomaterial and the autonomous environmental responsiveness of living elements, heralding a new era of biotherapeutics in addressing human health concerns. Here, our review aims at presenting an overview of the status of the oral delivery of living material from a biological, technical, and practical perspective, describing the clinical significance and potential, the current technological development and dilemma, as well as the prospect.
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| 43. |
- Lüchow, Mads, et al.
(author)
-
Modular, synthetic, thiol-ene mediated hydrogel networks as potential scaffolds for 3D cell cultures and tissue regeneration
- 2020
-
In: Journal of Polymer Science. - : John Wiley and Sons Inc. - 2642-4150 .- 2642-4169. ; 58:22, s. 3153-3164
-
Journal article (peer-reviewed)abstract
- Natural polymers such as collagen are popular materials for tissue engineering scaffolds due to their innate bioactivity and biocompatibility. Being derived from animal sources, however, means that batch-to-batch consistency is often low and the extraction of collagen is costly. This conundrum facilitates the need for synthetic alternatives as scaffolding materials. In this study, a system of poly(ethylene glycol) (PEG)-based thiol-ene coupled (TEC) hydrogel scaffolds is presented for tissue engineering purposes. The platform includes several necessary features, namely cytocompatibility, high swelling ability, biodegradability, tunable stiffness, and fast, straightforward fabrication. The swelling ability is provided by the hydrophilicity of the ether-links of PEG, which facilitated the formation of high water content hydrogels that match the water content of soft tissues for the proper diffusion of nutrients and waste compounds. TEC ensures fast and facile fabrication, with cross-linking moieties that allow for the biodegradation of the hydrogel network through hydrolytic cleavage. The mechanical properties of the scaffolds are made tunable in the range of storage moduli spanning <1 kPa to >100 kPa. It is also shown that despite the synthetic nature of the hydrogels, human dermal fibroblasts and murine macrophages, Raw 264.7, were able to survive and produce extracellular protein excretions while embedded in the 3D hydrogels.
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| 44. |
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| 45. |
- Malkoch, Michael, 1974-, et al.
(author)
-
CHAPTER 1 : Introduction to dendrimers and other dendritic polymers
- 2020
-
In: Monographs in Supramolecular Chemistry. - Cambridge : Royal Society of Chemistry. ; , s. 1-20
-
Conference paper (peer-reviewed)abstract
- This chapter will provide a descriptive overview of the different classes that define dendritic polymers and their subcategories. These include monodisperse dendrons and dendrimers as well as polydisperse hyperbranched polymers, linear-dendritic copolymer hybrids, dendronized polymers and dendrigrafts. Its content will give the reader interested in venturing into the field of dendritic polymers, the general synthetic options with respect to choice of scaffolds. From a researcher point of view, a major drawback to exploiting this class of polymers is strongly related to their accessibility, especially synthetically challenging and flawless dendritic scaffolds. As monodisperse dendrimers are the pinnacle of dendritic polymers that are synthesized via a cascade of successful reactions steps, it is pivotal that chemists utilize reactions known for their robustness and simple purification. Consequently, a large part of this chapter describes previous and recent synthetic approaches to dendrimers that have successfully been accomplished, such as traditional and accelerated growth strategies, as well as their pros and cons. A rationale on how to synthetically approach dendrimers is provided, from choice of monomers, growth route and pitfalls that accompany their construction. More in-depth synthetic description and their related references for structurally specific architectures can be found in the later chapters in this book.
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| 46. |
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| 47. |
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| 48. |
- Martin-Serrano Ortiz, Angela, et al.
(author)
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Design of multivalent fluorescent dendritic probes for site-specific labeling of biomolecules
- 2018
-
In: Journal of Polymer Science Part A. - : WILEY. - 0887-624X .- 1099-0518. ; 56:15, s. 1609-1616
-
Journal article (peer-reviewed)abstract
- Herein, the synthesis and characterization of orthogonal dendrons decorated with multiple units of fluorescent and a chemoselective group at a focal point, followed by specific antibody labeling, is presented. Fluorescence results confirm the applicability of the fluorescent probes for biomolecule labeling and fluorescent signal amplification.
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| 49. |
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| 50. |
- Namata, Faridah
(author)
-
Cationic Dendritic Polymers and Their Hybridization with Cellulose Nanofibrils
- 2023
-
Doctoral thesis (other academic/artistic)abstract
- Antimicrobial resistance (AMR) is one of the major global threats to thehealth of humans, animals, plants and ecosystems. AMR arises whenbacteria, viruses, fungi, and parasites undergo changes over time; makingmedicines such as antibiotics, antivirals, antifungals and antiparasiticineffective at treating infections. In 2014, it caused approximately 700 000deaths worldwide which increased to 1.27 million deaths in 2019.Consequently, there is a need to explore novel technologies andtreatments. Within the development of alternatives to conventional smallmoleculeantibiotics, polycationic macromolecules have emerged, such asdendritic polymers and their nanomaterials.Dendrimers are high precision, branched macromolecules with a highdensity of terminal functional groups. Their unique architecture and abilityfor precise control over both shape and surface functionality make themsuitable for biomedical applications such as drug delivery, gene deliveryand antimicrobials.Cellulose nanofibrils (CNFs) are nanoscale fibrils of cellulose, an abundantpolymer typically derived from wood. The prolonged reliance on fossilbasedproducts is associated with a wide range of adverse environmentalconsequences which have prompted the exploration of raw materialsderived from renewable resources. The intriguing properties of CNFs, suchas high elastic moduli and low densities, have made them attractive asstructural materials from sustainable sources that can form 3D networks.The combination of cationic dendritic polymers and cellulose nanofibrils isexplored in this thesis and presents an exciting avenue for the developmentof innovative biomaterials with antibacterial properties andbiocompatibility. Part of the work focuses on the synthesis of cationicdendritic polymers, with varying types of cationic groups at the peripheralthrough the use of fluoride-promoted esterification chemistry and thioleneclick reactions. Another part focuses on creating crosslinked hybridhydrogels using cationic dendrimers and anionic CNFs. Finally, a part ofthe thesis presents the preparation of hydrogels consisting of dendriticlinear-dendritic (DLD) polymer solutions and anionic CNFs. Overall, thefindings showcase the versatility and promise of the developed cationicdendritic polymers and CNF-based hydrogels against Escherichia coli,Pseudomonas aeruginosa and Staphylococcus aureus bacterial strainswhilst exhibiting low cytotoxicity.
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