Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, Shandong, 266021, P. R. China.
School of Basic Medicine, College of Medicine, Qingdao University, Qingdao, Shandong, 266071, P. R. China.
Adv Healthc Mater. 2022 Jul;11(13):e2102818. doi: 10.1002/adhm.202102818. Epub 2022 Mar 27.
Various scaffolding systems have been attempted to facilitate vascularization in tissue engineering by optimizing biophysical properties (e.g., vascular-like structures, porous architectures, surface topographies) or loading biochemical factors (e.g., growth factors, hormones). However, vascularization during ossification remains an unmet challenge that hampers the repair of large bone defects. In this study, reconstructing vascularized bones in situ against critical-sized bone defects is endeavored using newly developed scaffolds made of chemically cross-linked gelatin microsphere aggregates (C-GMSs). The rationale of this design lies in the creation and optimization of cell-material interfaces to enhance focal adhesion, proliferation, and function of anchorage-dependent functional cells. In vitro trials are carried out by coculturing human aortic endothelial cells (HAECs) and murine osteoblast precursor cells (MC3T3-E1) within C-GMS scaffolds, in which endothelialized bone-like constructs are yielded. Angiogenesis and osteogenesis induced by C-GMSs scaffold are further confirmed via subcutaneous-embedding trials in nude mice. In situ trials for the repair of critical-sized femoral defects are subsequently performed in rats. The acellular C-GMSs with interconnected macropores, exhibit the capability to recruit the endogenous cells (e.g., bone-forming cells, vascular forming cells, immunocytes) and then promote vascularized bone regeneration as well as integration with host bone.
各种支架系统已被尝试通过优化生物物理特性（例如，类似血管的结构、多孔架构、表面形貌）或加载生化因子（例如，生长因子、激素）来促进组织工程中的血管生成。然而，成骨过程中的血管化仍然是一个未满足的挑战，这阻碍了大骨缺损的修复。在这项研究中，使用新开发的由化学交联明胶微球聚集体（C-GMS）制成的支架，努力在原位重建针对临界尺寸骨缺损的血管化骨骼。这种设计的原理在于创建和优化细胞-材料界面，以增强锚定依赖性功能细胞的粘着斑、增殖和功能。通过将人主动脉内皮细胞（HAECs）和鼠成骨前体细胞（MC3T3-E1）共培养在 C-GMS 支架内进行体外试验，其中产生了内皮化的骨样结构。通过裸鼠皮下植入试验进一步证实了 C-GMS 支架诱导的血管生成和成骨作用。随后在大鼠中进行了原位修复临界尺寸股骨缺损的试验。具有互连通孔的无细胞 C-GMS 具有募集内源性细胞（例如，成骨细胞、血管形成细胞、免疫细胞）的能力，然后促进血管化骨再生以及与宿主骨的整合。
