Biomedical Materials Science, School of Dentistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
Microbiology and Immunology, School of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
Macromol Biosci. 2019 Sep;19(9):e1900142. doi: 10.1002/mabi.201900142. Epub 2019 Aug 2.
Emphasizing the role of hydrogel stiffness and cellular differentiation, this study develops collagen and elastin-like polypeptide (ELP)-based bone regenerative hydrogels loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) and doxycycline with mechanical properties suitable for osteogenesis. The drug-incorporated collagen-ELP hydrogels has significantly higher modulus of 35 ± 5 kPa compared to collagen-only hydrogels. Doxycycline shows a bi-phasic release with an initial burst release followed by a gradual release, while rhBMP-2 exhibits a nearly linear release profile for all hydrogels. The released doxycycline shows anti-microbial activity against Pseudomonas aeruginosa, Streptococcus sanguinis, and Escherichia coli. Microscopic observation of the hydrogels reveals their interconnected, macroporous, 3D open architecture with pore diameters between 160 and 400 µm. This architecture supports human adipose-derived stem cell attachment and proliferation from initial days of cell seeding, forming a thick cellular sheath by day 21. Interestingly, in collagen and collagen-ELP hydrogels, cell morphology is elongated with stretched slender lamellipodial formation, while cells assemble as spheroidal aggregates in crosslinked as well as drug-loaded hydrogels. Osteogenic markers, alkaline phosphatase and osteocalcin, are expressed maximally for drug-loaded hydrogels compared to those without drugs. The drug-loaded collagen-ELP hydrogels are thus promising for combating bacterial infection and promoting guided bone regeneration.
强调水凝胶硬度和细胞分化的作用，本研究开发了基于胶原蛋白和弹性蛋白样多肽（ELP）的骨再生水凝胶，负载重组人骨形态发生蛋白-2（rhBMP-2）和强力霉素，具有适合成骨的机械性能。与仅含胶原蛋白的水凝胶相比，载药的胶原蛋白-ELP 水凝胶的模量显著提高到 35±5kPa。强力霉素表现出双相释放，初始突释后逐渐释放，而 rhBMP-2 所有水凝胶均表现出近线性释放。释放的强力霉素对铜绿假单胞菌、血链球菌和大肠杆菌具有抗菌活性。水凝胶的微观观察显示它们具有相互连接的、大孔的、3D 开放式结构，孔径在 160 至 400μm 之间。这种结构支持人脂肪来源的干细胞附着和增殖，从细胞接种的最初几天开始，到第 21 天形成厚厚的细胞鞘。有趣的是，在胶原蛋白和胶原蛋白-ELP 水凝胶中，细胞形态拉长，形成伸展的细长片状伪足，而在交联和载药水凝胶中，细胞聚集形成球形聚集体。与不含药物的水凝胶相比，载药水凝胶中碱性磷酸酶和骨钙素的表达最大。因此，载药的胶原蛋白-ELP 水凝胶有望用于对抗细菌感染和促进引导骨再生。
