Department of Breast Surgery, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang 110042, People's Republic of China.
State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China.
Biofabrication. 2023 Feb 9;15(2). doi: 10.1088/1758-5090/acb6b8.
Craniofacial bone regeneration is a coupled process of angiogenesis and osteogenesis, which, associated with infection, still remains a challenge in bone defects after trauma or tumor resection. 3D tissue engineering scaffolds with multifunctional-therapeutic properties can offer many advantages for the angiogenesis and osteogenesis of infected bone defects. Hence, in the present study, a microchannel networks-enriched 3D hybrid scaffold composed of decellularized extracellular matrix (dECM), gelatin (Gel), quaterinized chitosan (QCS) and nano-hydroxyapatite (nHAp) (dGQH) was fabricated by an extrusion 3D bioprinting technology. And enlightened by the characteristics of natural bone microstructure and the demands of vascularized bone regeneration, the exosomes (Exos) isolated from human adipose derived stem cells as angiogenic and osteogenic factors were then co-loaded into the desired dGQHhybrid scaffold based on an electrostatic interaction. The results of the hybrid scaffolds performance characterization showed that these hybrid scaffolds exhibited an interconnected pore structure and appropriate degradability (>61% after 8 weeks of treatment), and the dGQHhybrid scaffold displayed the highest porosity (83.93 ± 7.38%) and mechanical properties (tensile modulus: 62.68 ± 10.29 MPa, compressive modulus: 16.22 ± 3.61 MPa) among the dGQH hybrid scaffolds. Moreover, the dGQHhybrid scaffold presented good antibacterial activities (against 94.90 ± 2.44% ofand 95.41 ± 2.65% of, respectively) as well as excellent hemocompatibility and biocompatibility. Furthermore, the results of applying the Exos to the dGQHhybrid scaffold showed that the Exo promoted the cell attachment and proliferation on the scaffold, and also showed a significant increase in osteogenesis and vascularity regeneration in the dGQH@Exo scaffoldsand. Overall, this novel dECM/Gel/QCS/nHAp hybrid scaffold laden with Exo has a considerable potential application in reservation of craniofacial bone defects.
颅颌面骨再生是血管生成和成骨的偶联过程，与感染相关，仍然是创伤或肿瘤切除后骨缺损的一个挑战。具有多功能治疗特性的 3D 组织工程支架可为感染性骨缺损的血管生成和成骨提供许多优势。因此，在本研究中，通过挤出 3D 生物打印技术制备了一种由脱细胞细胞外基质（dECM）、明胶（Gel）、季铵化壳聚糖（QCS）和纳米羟基磷灰石（nHAp）组成的富含微通道网络的 3D 杂化支架（dGQH）。并且，受天然骨微结构特征和血管化骨再生需求的启发，将从人脂肪源性干细胞中分离出的作为血管生成和成骨因子的外泌体（Exos）基于静电相互作用共加载到所需的 dGQH 杂化支架中。杂化支架性能表征的结果表明，这些杂化支架具有相互连通的孔结构和适当的降解性（处理 8 周后>61%），并且 dGQH 杂化支架具有最高的孔隙率（83.93±7.38%）和机械性能（拉伸模量：62.68±10.29MPa，压缩模量：16.22±3.61MPa）。此外，dGQH 杂化支架表现出良好的抗菌活性（分别对 94.90±2.44%和 95.41±2.65%）以及优异的血液相容性和生物相容性。此外，将 Exos 应用于 dGQH 杂化支架的结果表明，Exos 促进了细胞在支架上的附着和增殖，并且还显示出 dGQH@Exo 支架中骨生成和血管再生的显著增加。总体而言，这种新型的负载 Exos 的 dECM/Gel/QCS/nHAp 杂化支架在保留颅颌面骨缺损方面具有相当大的应用潜力。
