Department of Nanobiochemistry, Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-Minamimachi, Kobe 650-0047, Japan.
Biomater Sci. 2018 Feb 27;6(3):550-561. doi: 10.1039/c7bm01167a.
Injectable hydrogels are biomaterials that have the potential to provide scaffolds to cells for in situ tissue regeneration with a minimally invasive implantation procedure. The success of in vivo tissue engineering utilizing injectable gels depends on providing cells with appropriate scaffolds that present an instructive extracellular microenvironment, which strongly influences the survival, proliferation, organization, and function of cells encapsulated within gels. One of the most important abilities of injectable gels to achieve this function is to adsorb and retain a wide variety of requisite bioactive molecules including nutrients, extracellular matrices, and growth/differentiation factors within gels. Previously, we developed nanocomposite injectable gels fabricated by simple combination of common biodegradable copolymers, poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG-PLGA), and synthetic clay nanoparticles (LAPONITE®). We revealed that the nanocomposite injectable gels strongly adsorb ECM molecules including collagen and heparin within gels and retain them due to the ability of LAPONITE® in synchronization with the degradation of PLGA-PEG-PLGA and subsequent release of the degradation products. Human dermal fibroblast cells cultured on the nanocomposite gels showed enough high cell viability and proliferation for at least a week. Moreover, various kinds of human cells encapsulated within the nanocomposite gels exhibited significantly higher survival, proliferation, and three-dimensional organization in comparison with the PLGA-PEG-PLGA gel, LAPONITE® gel, and Matrigel. Furthermore, transplantation of mouse myoblast cells with the nanocomposite gels in model mice of skeletal muscle injury dramatically enhanced tissue regeneration and functional recovery, whereas cell transplantation with the PLGA-PEG-PLGA gel did not. Thus, the nanocomposite injectable gels possess unique abilities to self-replenish the regenerative extracellular microenvironment within the gels in the body, demonstrating the potential utility of the nanocomposite injectable gels for in vivo tissue engineering.
可注射水凝胶是一种具有潜在能力的生物材料，可以为细胞提供支架，用于原位组织再生，采用微创植入程序。利用可注射凝胶进行体内组织工程的成功取决于为细胞提供适当的支架，这些支架提供了有指导意义的细胞外微环境，这强烈影响了包封在凝胶中的细胞的存活、增殖、组织和功能。可注射凝胶实现此功能的最重要能力之一是在凝胶内吸附和保留各种必需的生物活性分子，包括营养物质、细胞外基质和生长/分化因子。以前，我们通过简单地组合常见的可生物降解共聚物聚（乳酸-共-乙醇酸）-b-聚（乙二醇）-b-聚（乳酸-共-乙醇酸）（PLGA-PEG-PLGA）和合成粘土纳米颗粒（LAPONITE®）开发了纳米复合可注射凝胶。我们揭示了纳米复合可注射凝胶强烈吸附凝胶内的 ECM 分子，包括胶原蛋白和肝素，并由于 LAPONITE®的能力与 PLGA-PEG-PLGA 的降解同步，随后释放降解产物而保留它们。在纳米复合凝胶上培养的人真皮成纤维细胞显示出至少一周的足够高的细胞活力和增殖。此外，与 PLGA-PEG-PLGA 凝胶、LAPONITE®凝胶和 Matrigel 相比，封装在纳米复合凝胶内的各种人类细胞表现出显著更高的存活率、增殖率和三维组织。此外，在骨骼肌损伤模型小鼠中，将纳米复合凝胶与小鼠成肌细胞共移植极大地增强了组织再生和功能恢复，而与 PLGA-PEG-PLGA 凝胶的细胞移植则没有。因此，纳米复合可注射凝胶具有独特的自我补充凝胶内再生细胞外微环境的能力，证明了纳米复合可注射凝胶在体内组织工程中的潜在用途。
