期刊
BIOACTIVE MATERIALS
卷 26, 期 -, 页码 1-13出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2023.02.008
关键词
Parathyroid hormone; Dual -mode release; Thermosensitive hydrogel; Angiogenesis; Bone regeneration
Osteogenesis, osteoclastogenesis, and angiogenesis are crucial for bone regeneration. A novel NIR-activatable scaffold with dual-mode PTHrP-2 release capability was developed to promote osteogenesis and angiogenesis for high-efficacy bone regeneration. In vivo experiments confirmed its significant improvement of bone reparative effect.
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 weak-nesses 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 regen-eration, 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.
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