Successful regeneration of the cranium in patients suffering from cranial bone defects is an integral step to restore craniofacial function. However, restoration of craniofacial structure has been challenging due to its complex geometry, limited donor site availability, and poor graft integration. To address these problems, we investigated the use of a thiol-acrylate hydrogel as a cell carrier to facilitate cranial regeneration. Thiol-acrylate hydrogels were formulated with 5-15 wt% poly(ethylene glycol)-diacrylate (PEGDA) and 1-9 mm dithiothreitol (DTT). The degradation rate, swelling ratio, and shear modulus of the resulting hydrogel were first characterized. Then, pre-osteoblast-like cells (MC3T3-E1) were encapsulated in the hydrogel and cultured for up to 21 d. Our results demonstrate that compared to samples formulated from 15 wt% PEGDA, 5 wt% PEGDA samples showed lower storage modulus at day 10 (0.7 kPa versus 8.3 kPa), 62.7% higher in weight change after soaking for 10 d. While the 5 wt% PEGDA group showed an 85% weight loss between day 10 and 21, the 15 wt% PEGDA group showed a 5% weight gain in the same time period. Cell viability with 15 wt% PEGDA and 5 mm DTT hydrogel decreased by 41.3% compared to 5 wt% PEGDA and 5mM DTT gel at day 7. However, histological analysis of cells after 21 d in culture revealed that they had pericellular mineral deposition indicating that the cells were differentiating into osteoblasts lineage in all experimental groups. This study shows that thiol-acrylate hydrogels can be tailored to achieve different degradation rates, in order to enhance cell viability and differentiation. Thus, the findings of this study provide a fundamental understanding for the application of thiol-acrylate hydrogels in cranial bone regeneration.
Aim: This study investigated biodegradable thiol-acrylate hydrogels as stem cell carriers to facilitate cranial bone regeneration. Materials & methods: Two formulations of thiol-acrylate hydrogels (5 and 15 wt% Poly[ethylene glycol]-diacrylate [PEGDA] hydrogels) were used as stem cell carriers. Bone marrow mesenchymal stromal cells and dental pulp mesenchymal stromal cells were photoencapsulated and cultured in basal or osteogenic medium 3 days before the surgery. Using New Zealand White Rabbits, four defects (5 mm diameter and 2 mm thickness) were created and hydrogel scaffolds were implanted in each rabbit cranium for 6 weeks. Results & Conclusion: AlamarBlue assay showed increasing metabolic activity levels in 5 wt% PEGDA hydrogels than 15 wt% PEGDA hydrogels. Photoencapsulated-mesenchymal stromal cells in 15 wt% PEGDA hydrogels demonstrated significantly increasing alkaline phosphatase activity levels on day 7 compared with days 1 and 3. Histological diagnosis showed 5 wt% PEGDA hydrogels resulted in lower averaged residual gel areas than 15 wt% PEGDA hydrogel specimens and control groups 6 weeks postimplantation.
Aim: The study aimed to examine the impact of crosslinking BMP2 in biodegradable visible light-cured thiol-acrylate hydrogels. Materials & methods: BMP2 was photoencapsulated in 10 wt% PEG-diacrylate hydrogels with or without immortalized mouse bone marrow stromal cells (BMSC). Results & conclusion: Photoencapsulated-BMSC with BMP2 (BMBMP2) showed a significantly (p < 0.05) increased level in metabolic activity, by 54.61%, compared with photoencapsulated-BMSC at day 3. Furthermore, BMBMP2 groups showed significantly increased levels in ALP activity compared with BMSC at days, 1, 3, 7 (p < 0.01) and 10 (p < 0.05). This study shows promising results photoencapsulating BMP2 in thiol-acrylate hydrogels for craniofacial bone tissue engineering applications.
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