注射式纳米微囊功能支架维持工程化脂肪容积恒定的应用基础研究

Soft tissue defects resulting from traumatic injury, tumor resections, congenital defects or aging often lead to poor cosmesis, affect the emotional well-being of patients and even impair function. A promising approach to solving these problems is the adoption of tissue engineering principles and the use of injectable biodegradable materials. However, bioengineered grafts using injectable biomaterials alone often had inadequate neovascularization and post-operative volume reduction. With the development of new microcarriers technique, it brings new hope to the regeneration of fat tissue. In our previous study, we successfully synthesized an injectable gelatin derivative hydrogels with sustained vascular endothelial growth factor release for induced angiogenesis. However, how to maintain the shape of the bioengineered grafts has still not been resolved yet. In this program, we plan to develop a new multifunctional microcapsule, and select two factors , bFGF and VEGF which play a key role in the process of fat formation and vascularization, as a tool of drugs. Next, we embed bFGF in to this microcapsule with different release rates, finally we will establish a new release system (hydrogel-VEGF/microcapsule-bFGF). We will observe the interaction between ADSC and the biomaterials through the in vitro three-dimensional cell culture system. With the animal model, we will also observe the ability to regenerate fat tissue by these new biomaterials, using Micro-CT, and histological analysis. At last, we will optimize the dosage administration, these data will provide a basis for the development of the new injectable tissue engineering scaffolds.

水凝胶支架用于注射式脂肪组织工程存在血管化不足以及注射后移植物容积减少等问题，限制了其临床应用。课题组前期研制的水凝胶支架具有良好的促血管生成作用，结合新近有关微球用于软骨再生的研究，拟研制具有细胞募集性和控释效能的功能性纳米微囊支架。该功能支架选择在脂肪形成与血管化过程中起关键作用的生长因子bFGF和VEGF为工具药，制备水凝胶-VEGF/纳米微囊-bFGF复合系统，通过控制微囊内载药小球的粒径实现bFGF的可控释放，促进脂肪再生并达到良好血管化目标的同时，维持容积恒定。为达到上述目标，本研究拟初选控释标准，通过体外三维培养模型，观察人脂肪干细胞与复合材料的相互作用，进一步筛选bFGF给药剂量；通过动物模型，观察复合材料实现原位脂肪再生与血管化的能力，优化bFGF给药剂量和控释标准。为研制新型具有脂肪再生功能的注射式软组织工程支架材料提供依据，为利用生物材料手段进行再生医学研究提供基础。

水凝胶支架用于注射式脂肪组织工程存在血管化不足以及注射后移植物容积减少等问题，限制了其临床应用。课题组前期研制的水凝胶支架具有良好的促血管生成作用，结合新近有关微球用于软骨再生的研究，拟研制具有细胞募集性和控释效能的功能性纳米微囊支架。该功能支架选择在脂肪形成与血管化过程中起关键作用的生长因子bFGF和VEGF为工具药，制备水凝胶-VEGF/纳米微囊-bFGF复合系统，通过控制微囊内载药小球的粒径实现bFGF的可控释放，促进脂肪再生并达到良好血管化目标的同时，维持容积恒定。为达到上述目标，本研究拟初选控释标准，通过体外三维培养模型，观察人脂肪干细胞与复合材料的相互作用，进一步筛选bFGF给药剂量；通过动物模型，观察复合材料实现原位脂肪再生与血管化的能力，优化bFGF给药剂量和控释标准。为研制新型具有脂肪再生功能的注射式软组织工程支架材料提供依据，为利用生物材料手段进行再生医学研究提供基础。