Novel Biomaterial-Binding/Osteogenic Bi-Functional Peptide Binds to Silk Fibroin Membranes to Effectively Induce Osteogenesis In Vitro and In Vivo

• Published in: ACS applied materials & interfaces Vol. 15; no. 6; pp. 7673 - 7685
• Main Authors: Lyu, Ruyin, Chen, Yuping, Shuai, Yajun, Wang, Jie, Lu, Leihao, Cheng, Qichao, Cai, Jiangfeng, Mao, Chuanbin, Yang, Mingying
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 15.02.2023
• Subjects: adsorption; animal models; Animals; bacteriophages; biocompatible materials; Biocompatible Materials - pharmacology; Biological and Medical Applications of Materials and Interfaces; Bombyx mori; bone formation; bone morphogenetic proteins; Cell Differentiation; fibroins; Fibroins - pharmacology; Humans; Mesenchymal Stem Cells; Osteogenesis; peptides; Peptides - pharmacology; Rats; Silk - pharmacology; sowing; Tissue Scaffolds; peptides; binding; bone differentiation; biomaterials; mesenchymal stem cells
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.2c17554

Peptides can introduce new functions to biomaterials but their immobilization usually relies on inefficient physical adsorption or tedious chemical conjugation. Using the Bombyx mori silk fibroin (SF) membrane (SFm) as a model biomaterial, here, we demonstrate a universal strategy for discovering new peptides that can “stick” to a biomaterial to functionalize it. Specifically, two peptide motifs, one screened by phage display biopanning for binding to the biomaterial (i.e., SF) and another derived from an osteogenic growth factor (i.e., bone morphogenetic protein-2), are fused into a new chimeric peptide that can bind to SFm for more efficient osteogenesis. Theoretical simulations and experimental assays confirm that the chimeric peptide binds to SF with high affinity, facilely achieving its immobilization onto SFm. The peptide enables SFm to effectively induce osteogenic differentiation of human mesenchymal stem cells (MSCs) even without other osteogenic inducers and efficiently stimulate bone regeneration in a subcutaneous rat model in 8 weeks, even without MSC seeding, while not causing inflammatory responses. Since biomaterial-binding peptides can be readily screened using phage display and functional peptides can be generated from growth factors, our work suggests a universal strategy for combining them to seek new peptides for binding and functionalizing biomaterials.