| 1. |
- Ahlinder, Astrid, et al.
(author)
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Medical grade polylactide, copolyesters and polydioxanone : Rheological properties and melt stability
- 2018
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In: Polymer testing. - : ELSEVIER SCI LTD. - 0142-9418 .- 1873-2348. ; 72, s. 214-222
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Journal article (peer-reviewed)abstract
- Rheological measurements have shown that lactide-based copolymers with L-lactide content between 50 and 100 mol% with varying comonomers, as well as polydioxanone (PDX), can be used in additive manufacturing analogously to poly(L-lactide) (PLLA) if their melt behaviour are balanced. The results indicate that copolymers can be melt processed if the temperature is adjusted according to the melting point, and parameters such as the speed are tuned to conteract the elastic response. Small amplitude oscillatory shear (SAOS) rheology, thermal and chemical characterisation allowed us to map the combined effect of temperature and frequency on the behaviour of six degradable polymers and their melt stability. Values of complex viscosity and Tan delta obtained through nine time sweeps by varying temperature and frequency showed that the molecular structure and the number of methylene units influenced the results, copolymers of L-lactide with D-Lactide (PDLLA) or glycolide (PLGA) had an increased elastic response, while copolymers with trimethylene carbonate (PLATMC) or epsilon-caprolactone (PCLA) had a more viscous behaviour than PLLA, with respect to their relative melting points. PDLLA and PLGA require an increased temperature or lower speed when processed, while PLATMC and PCLA can be used at a lower temperature and/or higher speed than PLLA. PDX showed an increased viscosity compared to PLLA but a similar melt behaviour. Negligible chain degradation were observed, apart from PLGA.
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| 2. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
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Enhancing the Properties of Poly(epsilon-caprolactone) by Simple and Effective Random Copolymerization of epsilon-Caprolactone with p-Dioxanone
- 2019
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In: Biomacromolecules. - : AMER CHEMICAL SOC. - 1525-7797 .- 1526-4602. ; 20:8, s. 3171-3180
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Journal article (peer-reviewed)abstract
- We have developed a straightforward strategy to obtain semicrystalline and random copolymers of epsilon-caprolactone (CL) and p-dioxanone (DX) with thermal stabilities similar to poly(epsilon-caprolactone), PCL, but with a faster- hydrolytic degradation rate-CL/DX-copolymers-are promising inks when printing scaffolds aimed for tissue engineering. Such copolymers behave similar to PCL and resorb faster. The copolymers were synthesized by bulk ring-opening copolymerization, achieving a high yield; a molecular weight, M-n, of 57-176 kg mol(-1); and an inherent viscosity of 1.7-1.9 dL g(-1). The copolymer microstructure consisted of long CL blocks that are separated by isolated DX units. The block length and the melting point were a linear function of the DX content. The copolymers crystallize as an orthorhombic lattice that is typical for PCL, and they formed more elastic, softer, and less hydrophobic films with faster degradation rates than PCL. Relatively high thermal degradation temperatures (above 250 C), similar to PCL, were estimated by thermogravimetric analysis, and copolymer filaments for three-dimensional printing and scaffolds were produced without thermal degradation.
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| 3. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
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Minimizing the time gap between service lifetime and complete resorption of degradable melt-spun multifilament fibers
- 2019
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In: Polymer degradation and stability. - : Elsevier. - 0141-3910 .- 1873-2321. ; 163, s. 43-51
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Journal article (peer-reviewed)abstract
- We have succeeded to modulated the degradation rate of poly(L-lactide) (PLLA) melt-spun multifilament fibers to extend the service lifetime and increase the resorption rate by using random copolymers of L-lactide and trimethylene carbonate (TMC). The presence of TMC units enabled an overall longer service lifetime but faster degradation kinetics than PLLA. By increasing the amount of TMC up to 18 mol%, multifilament fibers characterized by a homogenous degradation profile could be achieved. Such composition allowed, once the mechanical integrity was lost, a much longer retention of mechanical integrity and a faster rate of mass loss than samples containing less TMC. The degradation profile of multifilament fibers consisting of (co)polymers containing 0, 5, 10 and 18 mol% of TMC has been identified during 45 weeks in vitro hydrolysis following the molecular weight decrease, mass loss and changes in microstructure, crystallinity and mechanical properties. The fibers degraded by a two-step, autocatalyzed bulk hydrolysis mechanism. A high rate of molecular weight decrease and negligible mass loss, with a consequent drop of the mechanical properties, was observed in the early stage of degradation for fibers having TMC content up to 10 mol%. The later stage of degradation was, for these samples, characterized by a slight increase in the mass loss and a negligible molecular weight decrease. Fibers prepared with the 18 mol% TMC copolymer showed instead a more homogenous molecular weight decrease ensuring mechanical integrity for longer time and faster mass loss during the later stage of degradation.
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| 4. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
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Poly(L-lactide) and Poly(L-lactide-co-trimethylene carbonate) Melt-Spun Fibers : Structure-Processing-Properties Relationship
- 2019
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In: Biomacromolecules. - : AMER CHEMICAL SOC. - 1525-7797 .- 1526-4602. ; 20:3, s. 1346-1361
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Journal article (peer-reviewed)abstract
- l-Lactide/trimethylene carbonate copolymers have been produced as multifilament fibers by high-speed melt-spinning. The relationship existing between the composition, processing parameters and physical properties of the fibers has been disclosed by analyzing how the industrial process induced changes at the macromolecular level, i.e., the chain microstructure and crystallinity development. A poly(l-lactide) and three copolymers having trimethylene carbonate contents of 5, 10 and 18 mol % were synthesized with high molecular weight (M n ) up to 377 kDa and narrow dispersity. Their microstructure, crystallinity and thermal properties were dictated by the composition. The spinnability was then assessed for all the as-polymerized materials: four melt-spun multifilament fibers with increasing linear density were collected for each (co)polymer at a fixed take-up speed of 1800 m min -1 varying the mass throughput during the extrusion. A linear correlation resulted between the as-spun fiber properties and the linear density. The as-spun fibers could be further oriented, developing more crystallinity and improving their tensile properties by a second stage of hot-drawing. This ability was dependent on the composition and crystallinity achieved during the melt-spinning and the parameters selected for the hot-drawing, such as temperature, draw ratio and input speed. The crystalline structure evolved to a more stable form, and the degree of crystallinity increased from 0-52% to 25-66%. Values of tensile strength and Young's modulus up to 0.32-0.61 GPa and 4.9-8.4 GPa were respectively achieved.
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| 5. |
- Fuoco, Tiziana, et al.
(author)
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Redox-Responsive Disulfide Cross-Linked PLA-PEG Nanoparticles
- 2017
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In: Macromolecules. - : AMER CHEMICAL SOC. - 0024-9297 .- 1520-5835. ; 50:18, s. 7052-7061
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Journal article (peer-reviewed)abstract
- We have developed a strategy for the preparation of redox-responsive PEG PLA-based nanoparticles containing disulfide bonds that can be disassembled in the presence of cellular concentrations of glutathione. Functionalized poly-(lactide)s were prepared by ring-opening copolymerization of L-lactide and 3-methyl-6-(tritylthiomethyl)-1,4-dioxane-2,5-dione, a monomer bearing a pendant trityl-thiol group, followed by the postpolymerization modification of trityl-thiol into pyridyl disulfide groups. Polymeric networks composed of PLA and PEG blocks linked by disulfide bonds were prepared by a disulfide exchange reaction between the functionalized PLAs and telechelic PEG having thiol groups at both ends, HS-PEG-SH, in DMF. When dialyzed against water, they assembled into dispersible nanoparticles, with a flowerlike structure having a hydrophobic core and a hydrophilic shell, with sizes in the range 167-300 nm that are suitable for drug delivery. The effects of the number of functional groups, molecular weight, and concentration on the nanoparticle size were evaluated. The stability of the nanoparticles after dilution and the redox-responsive behavior in the presence of different concentrations of glutathione were assessed. The hydrophobic molecule Nile red could be encapsulated in the nanoparticles and then released in the presence of glutathione at cellular concentration.
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| 6. |
- Kleinhans, C., et al.
(author)
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A perfusion bioreactor system efficiently generates cell-loaded bone substitute materials for addressing critical size bone defects
- 2015
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In: Biotechnology Journal. - : Wiley-VCH Verlagsgesellschaft. - 1860-6768 .- 1860-7314. ; 10:11, s. 1727-1738
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Journal article (peer-reviewed)abstract
- Critical size bone defects and non-union fractions are still challenging to treat. Cell-loaded bone substitutes have shown improved bone ingrowth and bone formation. However, a lack of methods for homogenously colonizing scaffolds limits the maximum volume of bone grafts. Additionally, therapy robustness is impaired by heterogeneous cell populations after graft generation. Our aim was to establish a technology for generating grafts with a size of 10.5 mm in diameter and 25 mm of height, and thus for grafts suited for treatment of critical size bone defects. Therefore, a novel tailor-made bioreactor system was developed, allowing standardized flow conditions in a porous poly(L-lactide-co-caprolactone) material. Scaffolds were seeded with primary human mesenchymal stem cells derived from four different donors. In contrast to static experimental conditions, homogenous cell distributions were accomplished under dynamic culture. Additionally, culture in the bioreactor system allowed the induction of osteogenic lineage commitment after one week of culture without addition of soluble factors. This was demonstrated by quantitative analysis of calcification and gene expression markers related to osteogenic lineage. In conclusion, the novel bioreactor technology allows efficient and standardized conditions for generating bone substitutes that are suitable for the treatment of critical size defects in humans.
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| 7. |
- Munir, Arooj, et al.
(author)
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Efficacy of copolymer scaffolds delivering human demineralised dentine matrix for bone regeneration
- 2019
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In: Journal of Tissue Engineering. - : SAGE PUBLICATIONS INC. - 2041-7314. ; 10
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Journal article (peer-reviewed)abstract
- Poly(L-lactide-co-epsilon-caprolactone) scaffolds were functionalised by 10 or 20 mu g/mL of human demineralised dentine matrix. Release kinetics up to 21 days and their osteogenic potential on human bone marrow stromal cells after 7 and 21 days were studied. A total of 390 proteins were identified by mass spectrometry. Bone regeneration proteins showed initial burst of release. Human bone marrow stromal cells were cultured on scaffolds physisorbed with 20 mu g/mL and cultured in basal medium (DDM group) or physisorbed and cultured in osteogenic medium or cultured on non-functionalised scaffolds in osteogenic medium. The human bone marrow stromal cells proliferated less in demineralised dentine matrix group and activated ERK/1/2 after both time points. Cells on DDM group showed highest expression of IL-6 and IL-8 at 7 days and expressed higher collagen type 1 alpha 2, SPP1 and bone morphogenetic protein-2 until 21 days. Extracellular protein revealed higher collagen type 1 and bone morphogenetic protein-2 at 21 days in demineralised dentine matrix group. Cells on DDM group showed signs of mineralisation. The functionalised scaffolds were able to stimulate osteogenic differentiation of human bone marrow stromal cells.
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| 8. |
- Ojansivu, Miina, et al.
(author)
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Wood-based nanocellulose and bioactive glass modified gelatin-alginate bioinks for 3D bioprinting of bone cells
- 2019
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In: Biofabrication. - : Institute of Physics Publishing (IOPP). - 1758-5082 .- 1758-5090. ; 11:3
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Journal article (peer-reviewed)abstract
- A challenge in the extrusion-based bioprinting is to find a bioink with optimal biological and physicochemical properties. The aim of this study was to evaluate the influence of wood-based cellulose nanofibrils (CNF) and bioactive glass (BaG) on the rheological properties of gelatin-alginate bioinks and the initial responses ofbone cells embedded in these inks. CNF modulated the flow behavior of the hydrogels, thus improving their printability. Chemical characterization by SEM-EDX and ion release analysis confirmed the reactivity of the BaG in the hydrogels. The cytocompatibility of the hydrogels was shown to be good, as evidenced by the viability of human osteoblast-like cells (Saos-2) in cast hydrogels. For bioprinting, 4-layer structures were printed from cell-containing gels and crosslinked with CaCl2. Viability, proliferation and alkaline phosphatase activity (ALP) were monitored over 14 d. In the BaG-free gels, Saos-2 cells remained viable, but in the presence of BaG the viability and proliferation decreased in correlation with the increased viscosity. Still, there was a constant increase in the ALP activity in all the hydrogels. Further bioprinting experiments were conducted using human bone marrow-derived mesenchymal stem cells (hBMSCs), a clinically relevant cell type. Interestingly, hBMSCs tolerated the printing process better than Saos-2 cells and the ALP indicated BaG-stimulated early osteogenic commitment. The addition of CNF and BaG to gelatin-alginate bioinks holds great potential for bone tissue engineering applications.
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| 9. |
- Pappalardo, Daniela, et al.
(author)
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Biocompatibility of Resorbable Polymers : A Historical Perspective and Framework for the Future
- 2019
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In: Biomacromolecules. - : AMER CHEMICAL SOC. - 1525-7797 .- 1526-4602. ; 20:4, s. 1465-1477
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Journal article (peer-reviewed)abstract
- The history of resorbable polymers containing glycolide, lactide, e-caprolactone and trimethylene carbonate, with a special emphasis being placed on the time frame of the 1960s-1990s is described. Reviewing the history is valuable when looking into the future perspectives regarding how and where these monomers should be used. This story includes scientific evaluations indicating that these polymers are safe to use in medical devices, while the design of the medical device is not considered in this report. In particular, we present the data regarding the tissue response to implanted polymers, as well as the toxicity and pharmacokinetics of their degradation products. In the translation of these polymers from "the bench to the bedside," various challenges have been faced by surgeons, medical doctors, biologists, material engineers and polymer chemists. This Perspective highlights the visionary role played by the pioneers, addressing the problems that occurred on a case by case basis in translational medicine.
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| 10. |
- Ramani-Mohan, R. -K, et al.
(author)
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Deformation strain is the main physical driver for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation
- 2018
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In: Journal of Tissue Engineering and Regenerative Medicine. - : John Wiley and Sons Ltd. - 1932-6254 .- 1932-7005. ; 12:3, s. e1474-e1479
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Journal article (peer-reviewed)abstract
- Mesenchymal stem cells play a major role during bone remodelling and are thus of high interest for tissue engineering and regenerative medicine applications. Mechanical stimuli, that is, deformation strain and interstitial fluid-flow-induced shear stress, promote osteogenic lineage commitment. However, the predominant physical stimulus that drives early osteogenic cell maturation is not clearly identified. The evaluation of each stimulus is challenging, as deformation and fluid-flow-induced shear stress interdepend. In this study, we developed a bioreactor that was used to culture mesenchymal stem cells harbouring a strain-responsive AP-1 luciferase reporter construct, on porous scaffolds. In addition to the reporter, mineralization and vitality of the cells was investigated by alizarin red staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Quantification of the expression of genes associated to bone regeneration and bone remodelling was used to confirm alizarin red measurements. Controlled perfusion and deformation of the 3-dimensional scaffold facilitated the alteration of the expression of osteogenic markers, luciferase activity, and calcification. To isolate the specific impact of scaffold deformation, a computational model was developed to derive a perfusion flow profile that results in dynamic shear stress conditions present in periodically loaded scaffolds. In comparison to actually deformed scaffolds, a lower expression of all measured readout parameters indicated that deformation strain is the predominant stimulus for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation.
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| 11. |
- Sharma, Sunita, et al.
(author)
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Adenoviral Mediated Expression of BMP2 by Bone Marrow Stromal Cells Cultured in 3D Copolymer Scaffolds Enhances Bone Formation
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Journal article (peer-reviewed)abstract
- Selection of appropriate osteoinductive growth factors, suitable delivery method and proper supportive scaffold are critical for a successful outcome in bone tissue engineering using bone marrow stromal cells (BMSC). This study examined the molecular and functional effect of a combination of adenoviral mediated expression of bone morphogenetic protein-2 (BMP2) in BMSC and recently developed and characterized, biodegradable Poly(L-lactideco-epsilon-caprolactone){poly(LLA-co-CL)} scaffolds in osteogenic molecular changes and ectopic bone formation by using in vitro and in vivo approaches. Pathway-focused custom PCR array, validation using TaqMan based quantitative RT-PCR (qRT-PCR) and ALP staining showed significant up-regulation of several osteogenic and angiogenic molecules, including ALPL and RUNX2 in ad-BMP2 BMSC group grown in poly(LLA-co-CL) scaffolds both at 3 and 14 days. Micro CT and histological analyses of the subcutaneously implanted scaffolds in NOD/SCID mice revealed significantly increased radiopaque areas, percentage bone volume and formation of vital bone in ad-BMP2 scaffolds as compared to the control groups both at 2 and 8 weeks. The increased bone formation in the ad-BMP2 group in vivo was paralleled at the molecular level with concomitant over-expression of a number of osteogenic and angiogenic genes including ALPL, RUNX2, SPP1, ANGPT1. The increased bone formation in ad-BMP2 explants was not found to be associated with enhanced endochondral activity as evidenced by qRT-PCR (SOX9 and FGF2) and Safranin O staining. Taken together, combination of adenoviral mediated BMP-2 expression in BMSC grown in the newly developed poly(LLA-co-CL) scaffolds induced expression of osteogenic markers and enhanced bone formation in vivo.
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| 12. |
- Sharma, S., et al.
(author)
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Adenoviral mediated mono delivery of BMP2 is superior to the combined delivery of BMP2 and VEGFA in bone regeneration in a critical-sized rat calvarial bone defect
- 2019
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In: Bone Reports. - : Elsevier. - 2352-1872. ; 10
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Journal article (peer-reviewed)abstract
- Apart from osteogenesis, neovascularization of the defect area is an important determinant for successful bone healing. Accordingly, several studies have employed the combined delivery of VEGFA and BMP2 for bone regeneration. Nevertheless, the outcomes of these studies are highly variable. The aim of our study was to compare the effectiveness of adenoviral mediated delivery of BMP2 alone and in combination with VEGFA in rat bone marrow stromal cells (rBMSC)seeded on a poly(LLA-co-CL)scaffold in angiogenesis and osteogenesis using a critical-sized rat calvarial defect model. Both mono delivery of BMP2 and the combined delivery of a lower ratio of VEGFA and BMP2 (1:4)led to up-regulation of osteogenic genes (Alpl and Runx2)and increased calcium deposition in vitro, compared with the GFP control. Micro computed tomography (microCT)analysis of the rat calvarial defect at 8 weeks showed that the mono delivery of BMP2 (43.37 ± 3.55% defect closure)was the most effective in healing the bone defect, followed by the combined delivery of BMP2 and VEGFA (27.86 ± 2.89%)and other controls. Histological and molecular analyses supported the microCT findings. Analysis of the angiogenesis, however, showed that both mono delivery of BMP2 and combined delivery of BMP2 and VEGFA had similar angiogenic effect in the calvarial defects. Examination of the key genes related to host response against the adenoviral vectors showed that the current model system was not associated with adverse immune response. Overall, the results show that the mono delivery of BMP2 was superior to the combined delivery of BMP2 and VEGFA in healing the critical-sized rat calvarial bone defect. These findings underscore the importance of appropriate growth factor combination for the successful outcome in bone regeneration.
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| 13. |
- Sharma, Sunita, et al.
(author)
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Delivery of VEGFA in bone marrow stromal cells seeded in copolymer scaffold enhances angiogenesis, but is inadequate for osteogenesis as compared with the dual delivery of VEGFA and BMP2 in a subcutaneous mouse model
- 2018
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In: Stem Cell Research & Therapy. - : BioMed Central. - 1757-6512. ; 9
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Journal article (peer-reviewed)abstract
- Background: In bone tissue engineering (BTE), extensive research into vascular endothelial growth factor A (VEGFA)-mediated angiogenesis has yielded inconsistent results. The aim of this study was to investigate the influence on angio-and osteogenesis of adenoviral-mediated delivery of VEGFA alone or in combination with bone morphogenetic protein 2 (BMP2) in bone marrow stromal cells (BMSC) seeded onto a recently developed poly(LLA-co-CL) scaffold. Methods: Human BMSC were engineered to express VEGFA alone or in combination with BMP2 and seeded onto poly(LLA-co-CL) scaffolds. Changes in angiogenic and osteogenic gene and protein levels were examined by quantitative reverse-transcription polymerase chain reaction (RT-PCR), PCR array, and alkaline phosphatase assay. An in vivo subcutaneous mouse model was used to investigate the effect on angio-and osteogenesis of VEGFA alone or in combination with BMP2, using microcomputed tomography (mu CT), histology, immunohistochemistry, and immunofluorescence. Results: Combined delivery of a lower ratio (1: 3) of VEGFA and BMP2 (ad-BMP2 + VEGFA) led to upregulation of osteogenic and angiogenic genes in vitro at 3 and 14 days, compared with mono-delivery of VEGFA (ad-VEGFA) and other controls. In vivo, in a subcutaneous mouse model, both ad-VEGFA and ad-BMP2 + VEGFA scaffold explants exhibited increased angiogenesis at 2 weeks. Enhanced angiogenesis was largely related to the recruitment and differentiation of mouse progenitor cells to the endothelial lineage and, to a lesser extent, to endothelial differentiation of the implanted BMSC. mu CT and histological analyses revealed enhanced de novo bone formation only in the ad-BMP2 + VEGFA group, corresponding at the molecular level to the upregulation of genes related to osteogenesis, such as ALPL, RUNX2, and SPP1. Conclusions: Although BMSC expressing VEGFA alone or in combination with BMP2 significantly induced angiogenesis, VEGFA alone failed to demonstrate osteogenic activity both in vitro and in vivo. These results not only call into question the use of VEGFA alone in bone regeneration, but also highlight the importance in BTE of appropriately formulated combined delivery of VEGFA and BMP2.
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| 14. |
- Yassin, Mohammed A., et al.
(author)
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3D and Porous RGDC-Functionalized Polyester-Based Scaffolds as a Niche to Induce Osteogenic Differentiation of Human Bone Marrow Stem Cells
- 2019
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In: Macromolecular Bioscience. - : WILEY-V C H VERLAG GMBH. - 1616-5187 .- 1616-5195. ; 19:6
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Journal article (peer-reviewed)abstract
- Polyester-based scaffolds covalently functionalized with arginine-glycine-aspartic acid-cysteine (RGDC) peptide sequences support the proliferation and osteogenic differentiation of stem cells. The aim is to create an optimized 3D niche to sustain human bone marrow stem cell (hBMSC) viability and osteogenic commitment, without reliance on differentiation media. Scaffolds consisting of poly(lactide-co-trimethylene carbonate), poly(LA-co-TMC), and functionalized poly(lactide) copolymers with pendant thiol groups are prepared by salt-leaching technique. The availability of functional groups on scaffold surfaces allows for an easy and straightforward method to covalently attach RGDC peptide motifs without affecting the polymerization degree. The strategy enables the chemical binding of bioactive motifs on the surfaces of 3D scaffolds and avoids conventional methods that require harsh conditions. Gene and protein levels and mineral deposition indicate the osteogenic commitment of hBMSC cultured on the RGDC functionalized surfaces. The osteogenic commitment of hBMSC is enhanced on functionalized surfaces compared with nonfunctionalized surfaces and without supplementing media with osteogenic factors. Poly(LA-co-TMC) scaffolds have potential as scaffolds for osteoblast culture and bone grafts. Furthermore, these results contribute to the development of biomimetic materials and allow a deeper comprehension of the importance of RGD peptides on stem cell transition toward osteoblastic lineage.
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| 15. |
- Yassin, Mohammed A., et al.
(author)
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A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration
- 2017
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In: Macromolecular Bioscience. - : WILEY-V C H VERLAG GMBH. - 1616-5187 .- 1616-5195. ; 17:6
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Journal article (peer-reviewed)abstract
- Functionalizing polymer scaffolds with nanodiamond particles (nDPs) has pronounced effect on the surface properties, such as improved wettability, an increased active area and binding sites for cellular attachment and adhesion, and increased ability to immobilize biomolecules by physical adsorption. This study aims to evaluate the effect of poly(l-lactide-co-e-caprolactone) (poly(LLA-co-CL)) scaffolds, functionalized with nDPs, on bone regeneration in a rat calvarial critical size defect. Poly(LLA-co-CL) scaffolds functionalized with nDPs are also compared with pristine scaffolds with reference to albumin adsorption and seeding efficiency of bone marrow stromal cells (BMSCs). Compared with pristine scaffolds, the experimental scaffolds exhibit a reduction in albumin adsorption and a significant increase in the seeding efficiency of BMSCs (p = 0.027). In the calvarial defects implanted with BMSC-seeded poly(LLA-co-CL)/ nDPs scaffolds, live imaging at 12 weeks discloses a significant increase in osteogenic metabolic activity (p = 0.016). Microcomputed tomography, confirmed by histological data, reveals a substantial increase in bone volume (p = 0.021). The results show that compared with conventional poly(LLA-co-CL) scaffolds those functionalized with nDPs promote osteogenic metabolic activity and mineralization capacity. It is concluded that poly(LLA-co-CL) composite matrices functionalized with nDPs enhance osteoconductivity and therefore warrant further study as potential scaffolding material for bone tissue engineering.
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