Affiliation:
1. Department of Orthopedics Xiangya Hospital Central South University Changsha Hunan 410008 China
2. National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University Changsha Hunan 410008 China
3. Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan Province Changsha Hunan 410008 China
4. Department of Sports Medicine Xiangya Hospital Central South University Changsha Hunan 410008 China
Abstract
AbstractIn order to repair critical‐sized bone defects, various polylactic acid‐glycolic acid (PLGA)‐based hybrid scaffolds are successfully developed as bone substitutes. However, the byproducts of these PLGA‐based scaffolds are known to acidify the implanted site, inducing tiresome acidic inflammation. Moreover, these degradation productions cannot offer an osteo‐friendly microenvironment at the implanted site, matching natural bone healing. Herein, inspired by bone microenvironment atlas of natural bone‐healing process, an osteo‐microenvironment stage‐regulative scaffold (P80/D10/M10) is fabricated by incorporating self‐developed decellularized bone matrix microparticles (DBM‐MPs) and multifunctional magnesium hydroxide nanoparticles (MH‐NPs) into PLGA with an optimized proportion using low‐temperature rapid prototyping (LT‐RP) 3D‐printing technology. The cell experiments show that this P80/D10/M10 exhibits excellent properties in mechanics, biocompatibility, and biodegradability, meanwhile superior stimulations in osteo‐immunomodulation, angiogenesis, and osteogenesis. Additionally, the animal experiments determined that this P80/D10/M10 can offer an osteo‐friendly microenvironment in a stage‐matched pattern for enhanced bone regeneration, namely, optimization of early inflammation, middle neovascularization, and later bone formation. Furthermore, transcriptomic analysis suggested that the in vivo performance of P80/D10/M10 on bone defect repair is mostly attributed to regulating artery development, bone development, and bone remodeling. Overall, this study reveals that the osteo‐microenvironment stage‐regulative scaffold provides a promising treatment for bone defect repair.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Hunan Province
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)