Growth-Factor Free Multicomponent Nanocomposite Hydrogels That Stimulate Bone Formation
Growth-Factor Free Multicomponent Nanocomposite Hydrogels That Stimulate Bone Formation
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刺激骨形成的无生长因子多组分纳米复合水凝胶
DOI：
10.1002/adfm.201906205
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发表时间：
2020-02-16
影响因子：
19
通讯作者：
Mata, Alvaro
中科院分区：
文献类型：
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作者：
Okesola, Babatunde O.;Ni, Shilei;Mata, Alvaro
能够刺激和加速骨形成而不添加外源性细胞或生长因子的合成骨促进材料代表了老龄化世界人口的主要机会。报道了一种共组装系统，其整合了透明质酸酪胺（HA-Tyr）、生物活性肽两亲物（GHK-Cu 2+）和Laponite（Lap），以工程化具有物理、机械和生物分子信号的水凝胶，所述信号可以被调节以增强骨再生。多组分水凝胶的中心设计元素是自组装和酶介导的氧化偶联的整合，以优化结构和机械性能，并结合骨和血管促进片段以促进信号传导。光谱技术用于确认正交共价和超分子相互作用的相互作用，在多组分水凝胶形成。此外，物理机械表征表明，多组分水凝胶表现出改善的抗压强度，应力松弛曲线，低溶胀比，和延迟的酶促降解相比，单组分水凝胶。使用人间充质干细胞和人脐静脉内皮细胞在体外验证适用性，并且使用兔上颌窦底重建模型在体内验证适用性。用HA-Tyr-HA-Tyr-GHK-Cu 2+水凝胶处理的动物相对于包括市售Bio-Oss的对照表现出显著增强的骨形成。
Synthetic osteo-promoting materials that are able to stimulate and accelerate bone formation without the addition of exogenous cells or growth factors represent a major opportunity for an aging world population. A co-assembling system that integrates hyaluronic acid tyramine (HA-Tyr), bioactive peptide amphiphiles (GHK-Cu2+), and Laponite (Lap) to engineer hydrogels with physical, mechanical, and biomolecular signals that can be tuned to enhance bone regeneration is reported. The central design element of the multicomponent hydrogels is the integration of self-assembly and enzyme-mediated oxidative coupling to optimize structure and mechanical properties in combination with the incorporation of an osteo- and angio-promoting segments to facilitate signaling. Spectroscopic techniques are used to confirm the interplay of orthogonal covalent and supramolecular interactions in multicomponent hydrogel formation. Furthermore, physico-mechanical characterizations reveal that the multicomponent hydrogels exhibit improved compressive strength, stress relaxation profile, low swelling ratio, and retarded enzymatic degradation compared to the single component hydrogels. Applicability is validated in vitro using human mesenchymal stem cells and human umbilical vein endothelial cells, and in vivo using a rabbit maxillary sinus floor reconstruction model. Animals treated with the HA-Tyr-HA-Tyr-GHK-Cu2+ hydrogels exhibit significantly enhanced bone formation relative to controls including the commercially available Bio-Oss.