Self-Assembling Peptide Nanofibers Anchored Parathyroid Hormone Derivative for Bone Tissue Engineering

Abstract

Parathyroid hormone (PTH) has been used for bone regeneration through intermittent subcutaneous injection; however, the topical administration of PTH for bone repair remains challenging because of the overactivation of osteoclasts. Here, a PTH derivative, i.e., PTHrP-1, which exhibits enhanced osteogenesis and relatively reduced osteoclastogenesis, is anchored to RADA16-I to fabricate a novel self-assembling peptide, called P1R16. Firstly, P1R16 self-assembles into long nanofibers with PTHrP-1 exposed to the side end, which interacts with Type I collagen (Col) to form P1R16-Col composites. The RADA16 segment in P1R16 helps the sustained release of P1R16 from the composites. Secondly, the P1R16 self-assembling peptide nanofibers exhibit multiple functions. The nanofibers promote stem cell proliferation and recruitment, and then direct stem cell fate towards osteogenic differentiation but not adpipogenic differentiation, improving the quality of the regenerated bone. The nanofibers further promote bone regeneration through bone remodeling between osteoblasts and osteoclasts. Thirdly, the P1R16 self-assembling peptide nanofibers also promote the proliferation and recruitment of endothelial cells, which facilitate the vascularization of implants to support bone regeneration further. Overall, the P1R16 self-assembling peptide nanofibers maintain multiple functions, including pro-proliferation, direction of stem cell fate, bone remodeling and vascularization, showing considerable promise for bone tissue engineering to repair bone defects or fractures.

Keywords

Self-assembling peptide / Nanofiber / Parathyroid hormone / Bioactive factor / Bone regeneration

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Funding

the National Natural Science Foundation of China(81874232); the Key Research and Development Program of Hubei Province(2022BCA052); the Key Research and Development Program of Wuhan City(2023020402010591); the Fundamental Research Funds for the Central Universities(2042023kf0199); the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(ZNJC202014)