基于ADSC-EV血管诱导型3D打印仿生支架的 “后植法”乳房组织工程策略与机制研究

It is widely acknowledged that breast tissue engineering has broad application prospects in breast reconstruction after radical mastectomy. However, the bottleneck of its clinical treatment translation is the insufficient of grafts` vascularization, adipogenic microenvironment and adequate scaffold design for soft tissue, resulting in the difficulties in the reconstruction of large-size breast shaped graft in vivo. Our previous reseaches have demonstrated that human adipose derived stem cells- extracelluar vesicles(ADSC-EV) were capable in angiogenesis and improving fat survival rates. Meanwhile, we have developed a novel ADSC-EV surface modification strategy. Based on all mentioned pre-studies, the applicant for the first time supposed the “delayed implant” breat tissue engineering strategy with ADSC-EV modified 3D printing biomimetic scaffolds. Firstly, with the aid of CAD design and 3D printing technology, print a breast shaped PCL scaffold which is dual-biomimetic in shape and biomechanical property. Secondly, use ADSC-EV to modify this scaffold,and then subcutaneously implant it into nude mice for pre-vascularization. In accordance with the growing extent of neo-vessels and the decrease of inflammatory response, inject the ADSC-EV mixed fat grafts into the breast scaffold with multi-point injective methods, to reconstruct large-size breast shape grafts in vivo. We shall compare this novel strategy with tradiational tissue engineering method, for the purpose of determine its feasibility and priority. Finally we shall study the potential mechanism from the aspects of implanted ADSCs` survival and fate, in order to accelerate the clinical translation of breast tissue engineering.

利用乳房组织工程技术进行乳腺癌术后乳房再造具有较广阔的应用前景，但其临床转化瓶颈在于血管化不足及缺乏适合的软组织工程支架，导致大体积移植物体内构建困难。我们前期研究发现人脂肪干细胞来源胞外囊泡（ADSC-EV）可促进血管新生与颗粒脂肪存活，并已成功建立了基于ADSC-EV的支架表面修饰技术。基于此,申请人首次提出了基于ADSC-EV血管诱导型仿生支架的“后植法”乳房组织工程重建策略：首先通过CAD设计与3D打印技术制备生物力学与外型双重仿生的多孔聚己内酯乳房形态支架，再使用人ADSC-EV进行表面修饰后植入裸鼠皮下进行预血管化处理，随后将ADSC-EV与人颗粒脂肪混合物多点注射至支架内部，借助预构的血管化微环境构建大体积乳房形态移植物。我们将通过对比传统乳房组织工程策略，验证该策略的可行性与临床转化优越性，并从脂肪干细胞存活与命运转归的角度研究其机制，为乳房组织工程技术的临床转化提供新思路