Mengru Geng,Qianqian Zhang,Jiani Gu,Jin Yang,Haibo Du,Yating Jia,Xiaojun Zhou,Chuanglong He
Three-dimensional (3D) printed scaffolds provide a promising prospective for application in bone tissue engineering. 3D printed scaffolds with micro- and nano-fibrous structures that facilitate cell adhesion and migration, and combined vascularization and osteoinduction bioactivity will be ideal implants for bone defect repair. Here, we fabricated a 3D printed biodegradable poly (glycerol-co-sebacic acid-co-L-lactic acid-co-polyethylene glycol) (PGSLP)-based scaffold that was internally filled with gelatin nanofibers and allowed the local release of deferoxamine (DFO), which is essential for angiogenesis and osteogenesis in bone regeneration. The nanofibrous structured gelatin/PGSLP (NGP) scaffold was fabricated using a thermally induced phase separation (TIPS) technique, and the macroporous structured gelatin/PGSLP (MGP) scaffold was prepared by directly freeze-drying. The in vitro experiments demonstrated that both DFO-loaded NGP and DFO-loaded MGP scaffolds can promote the migration and tubular formation of human umbilical vein endothelial cells (HUVECs), and enhance the mineralized nodule formation and osteogenic-related gene expression during osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). In a rat critical-sized calvarial defect model, the results suggested that the scaffolds with DFO loading significantly promote the vascular formation and accelerate bone regeneration, while the enhancement of vascularization and osteogenesis in vivo in DFO-loaded NGP scaffold was better than that in DFO-loaded MGP scaffold. Therefore, the constructed PGLSP-based scaffolds with micro- and nano-fibrous structures would be promising candidates to match the structural and functional requirements for vascularized bone regeneration.
Yating Jia,Weizhong Wang,Xiaojun Zhou,Wei Nie,Liang Chen,Chuanglong He
Poly(glycerol sebacate) (PGS) has been explored extensively for tissue engineering applications due to its elastomeric mechanical properties and biocompatibility, but its relatively low mechanical strength and poor hydrophilicity restrict its practical applications in tissue engineering. In this study, we developed new biodegradable elastomeric copolyesters poly(glycerol-co-sebacic acid-co-L-lactic acid-co-polyethylene glycol) (PGSLP) by simultaneously introducing L-lactic acid (LLA) and polyethylene glycol (PEG) into the PGS network. The synthesized copolyesters were well-characterized to evaluate their physicochemical properties, mechanical strength and in vitro degradation properties, and their biocompatibility was also evaluated by a combination of in vivo and in vitro experiments. It is found that the PGSLP exhibited typical elastic properties, and possessed better hydrophilicity, water uptake capacity as well as improved degradation behaviors compared to PGS, which were beneficial for tissue engineering applications. More importantly, the physicochemical properties of PGSLP could be tuned in a wide range by changing the content of LLA and PEG, and their mechanical properties were visibly influenced by the curing conditions such as curing time. Furthermore, the L929 mouse fibroblast cells cultured on the PGSLP exhibited high viability, good spreading and proliferation, and PGSLP implants did not induce obvious inflammatory reaction but promoted neovascularization after subcutaneous implantation in Sprague-Dawley rats for 5 weeks. Hence, the developed PGSLP copolyesters may offer a much better choice of scaffolds than PGS for practical tissue engineering applications.
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