Drug-Loaded Elastin-Like Polypeptide-Collagen Hydrogels with High Modulus for Bone Tissue Engineering.
Drug-Loaded Elastin-Like Polypeptide-Collagen Hydrogels with High Modulus for Bone Tissue Engineering.
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DOI：
10.1002/mabi.201900142
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发表时间：
2019-08
影响因子：
4.6
通讯作者：
Pallabi Pal;Quynh C. Nguyen;Angela H Benton;M. Marquart;A. Janorkar
中科院分区：
文献类型：
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作者：
Pallabi Pal;Quynh C. Nguyen;Angela H Benton;M. Marquart;A. Janorkar
本研究强调水凝胶硬度和细胞分化的作用，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特性。与纯胶原蛋白水凝胶相比，掺有药物的胶原蛋白-ELP 水凝胶具有显着更高的模量（35 ± 5 kPa）。多西环素显示出双相释放，首先是突发释放，然后是逐渐释放，而 rhBMP-2 对所有水凝胶都表现出近乎线性的释放曲线。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。对水凝胶的显微镜观察揭示了它们相互连接的大孔 3D 开放结构，孔径在 160 至 400 µm 之间。这种结构支持人类脂肪干细胞从细胞接种的最初几天开始附着和增殖，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，细胞形态通过拉伸细长的片状足形成而被拉长，而细胞在交联和载药水凝胶中组装成球形聚集体。与不含药物的水凝胶相比，载药水凝胶的成骨标志物、碱性磷酸酶和骨钙素的表达量最大。因此，载药胶原-ELP水凝胶有望用于对抗细菌感染和促进引导骨再生。
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.