Despite the rapid development of the application of tissue engineering techniques in regenerative bone repair, the repair of severe pathologic bone defects, represented by osteoporotic bone defects, is still a huge challenge. Recent studies have identified local delivery of parathyroid hormone relative peptides (PTHrPs) as a novel pathway for bone repair as well, but how to load and locally release PTHrPs for good bone repair is a major obstacle. Here, a biopolymer of PLGA-PLL loaded with PTHrP1 is electrospunned into nanofiber membranes for guided bone regeneration. In vitro experiments show that PLGA-PLL synergized with PTHrP1 significantly promote osteogenic differentiation and angiogenesis, providing a favorable bone regeneration microenvironment. In vivo experiments show that the membrane recruits endogenous stem cells and promotes their ectopic osteogenic differentiation in an osteoporotic environment. Furthermore, the membrane can promote osteogenic differentiation and angiogenesis in situ and improve the local osteoporotic microenvironment, ultimately promoting the repair of bone defects. Therefore, present study provides a promising strategy for local delivery of PTH, which opens a new pathway for the treatment of osteoporotic bone defects.
Shi Liu,Zhengzhe Han,Ji-Na Hao,Dapeng Zhang,Xianglong Li,Yuanyuan Cao,Jinghuan Huang,Yongsheng Li
Osteogenesis, osteoclastogenesis, and angiogenesis play crucial roles in bone regeneration. Parathyroid hormone (PTH), an FDA-approved drug with pro-osteogenic, pro-osteoclastogenic and proangiogenic capabilities, has been employed for clinical osteoporosis treatment through systemic intermittent administration. However, the successful application of PTH for local bone defect repair generally requires the incorporation and delivery by appropriate carriers. Though several scaffolds have been developed to deliver PTH, they suffer from the weaknesses such as uncontrollable PTH release, insufficient porous structure and low mechanical strength. Herein, a novel kind of NIR-activable scaffold (CBP/MBGS/PTHrP-2) with dual-mode PTHrP-2 (a PTH derivative) release capability is developed to synergistically promote osteogenesis and angiogenesis for high-efficacy bone regeneration, which is fabricated by integrating the PTHrP-2-loaded hierarchically mesoporous bioactive glass (MBG) into the N-hydroxymethylacrylamide-modified, photothermal agent-doped, poly(N-isopropylacrylamide)-based thermosensitive hydrogels through assembly process. Upon on/off NIR irradiation, the thermoresponsive hydrogel gating undergoes a reversible phase transition to allow the precise control of on-demand pulsatile and long-term slow release of PTHrP-2 from MBG mesopores. Such NIR-activated dual-mode delivery of PTHrP-2 by this scaffold enables a well-maintained PTHrP-2 concentration at the bone defect sites to continually stimulate vascularization and promote osteoblasts to facilitate and accelerate bone remodeling. In vivo experiments confirm the significant improvement of bone reparative effect on critical-size femoral defects of rats. This work paves an avenue for the development of novel dual-mode delivery systems for effective bone regeneration.
Yi Wang,Yingkun Hu,Shenghui Lan,Zhe Chen,Yufeng Zhang,Xiaodong Guo,Lin Cai,Jingfeng Li
The local application of drug-loaded bioactive scaffold materials is one of the important directions to solve the clinical problem of osteoporotic (OP) bone defects. This study retains the advantages of drug loading and mechanical properties of natural 3D bioactive scaffolds. The scaffolds are functionally modified through chemical and self-assembly approaches with application of polydopamine (PDA) nanoparticles and parathyroid hormone-related peptide-1 (PTHrP-1) for efficient local drug loading. This study investigates the effects of the novel bioactive scaffolds on ossification, osteoclastogenesis, and macrophage polarization. This work elucidates the effects of the scaffolds in regulating osteoclastic activity and new bone formation in vitro. Further studies on the establishment and repair of OP bone defects in small animals are conducted, and the potential of natural bioactive porous scaffold materials to promote the repair of OP bone defects is initially verified. The preparation of safe and economical anti-OP bone repair material provides a theoretical basis for clinical translational applications.
危险品化学品经营许可证（带存储）