Poly(lactic-co-glycolic acid)-based composite bone-substitute materials

Research and development of the ideal artificial bone-substitute materials to replace autologous and allogeneic bones for repairing bone defects is still a challenge in clinical orthopedics.Recently,poly(lactic-co-glycolic acid)(PLGA)-based artificial bone-substitute materials are attracting increasing attention as the benefit of their suitable biocompatibility,degradability,mechanical properties,and capabilities to promote bone regeneration.In this article,we comprehensively review the artificial bone-substitute materials made from PLGA or the composites of PLGA and other organic and inorganic substances,elaborate on their applications for bone regeneration with or without bioactive factors,and prospect the challenges and opportunities in clinical bone regeneration.

A Novel Nano/Micro-Fibrous Scaffold by Melt-Spinning Method for Bone Tissue Engineering

In order to architecturally and functionally mimic native Extracellular Matrix （ECM）, a novel micro/nano-fibrous scaffold of hydroxyapetite/poly（lactide-co-glycolide） （HA/PLGA） composite was successfully prepared by melt-spinning method. A porous three-dimensional scaffold fabricated by melt-molding particulate-leaching method was used as control. This kind of scaffold comprising both nanofiber and microfiber had an original structure including a nano-network favorable for cell adhe- sion, and a micro-fiber providing a strong skeleton for support. The microfibers and nanofibers were blended homogeneously in scaffold and the compression strength reached to 6.27 MPa, which was close to human trabecular bone. The typical mi- cro/nano-fibrous structure was more benefcial for the proliferation and differentiation of Bone Mesenehymal Stem Cells （BMSCs）. The calcium deposition and Alkaline Phosphatase （ALP） activity were evaluated by the differentiation of BMSCs, and the results indicated that the temporary ECM was very beneficial for the differentiation of BMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, micro/nano-fibrous scaffold was used for the purpose of rapid bone remodeling in the defect area. The results showed that a distinct bony callus of bridging was observed at 12 weeks post-surgery and the expression of osteogenesis-related genes （bone-morphogenetic protein-2, Osteonectin, collagen-I） increased because of the ECM-like structure. Based on the results, the novel micro/nano-fibrous scaffold might be a promising candidate for bone tissue engi- neering.

Biofunctionalized composite scaffold to potentiate osteoconduction,angiogenesis,and favorable metabolic microenvironment for osteonecrosis therapy

Osteonecrosis is a common orthopedic disease in clinic,resulting in joint collapse if no appropriate treatment is performed in time.Core decompression is a general treatment modality for early osteonecrosis.However,effective bone regeneration in the necrotic area is still a significant challenge.This study developed a biofunctionalized composite scaffold(PLGA/nHA30VEGF)for osteonecrosis therapy through potentiation of osteoconduction,angiogenesis,and a favorable metabolic microenvironment.The composite scaffold had a porosity of 87.7%and compressive strength of 8.9 MPa.PLGA/nHA30VEGF had an average pore size of 227.6μm and a water contact angle of 56.5◦with a sustained release profile of vascular endothelial growth factor(VEGF).After the implantation of PLGA/nHA30VEGF,various osteogenic and angiogenic biomarkers were upregulated by 2-9 fold compared with no treatment.Additionally,the metabolomic and lipidomic profiling studies demonstrated that PLGA/nHA30VEGF effectively regulated the multiple metabolites and more than 20 inordinate metabolic pathways in osteonecrosis.The excellent performances reveal that the biofunctionalized composite scaffold provides an advanced adjuvant therapy modality for osteonecrosis.