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

Abstract

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.

Stem Cells and Bone Tissue Engineering

“…Yang M’s group designed chimeric peptide with one peptide motif that was bound to Bombyx mori silk fibroin (SF) membrane (SFm) and fused to peptide with the goal to promote osteogenesis in vitro and bone formation in vivo. The chimeric peptide enabled SFm to effectively induce osteogenic differentiation of human BMMSCs, even without other osteogenic inducers, and efficiently stimulated bone regeneration in a subcutaneous rat model in 8 weeks, even without MSC seeding, and not eliciting inflammatory responses [ 33 ].…”

“…BCP or TCP or hydroxyapatite scaffolds are not easily absorbable and often remain in the newly regenerated bone; these residues do not integrate with the host bone and likely offer inferior bone biomechanical properties. Bioactive growth factor peptide-conjugated scaffolds may be more suitable to deliver with stem cells, with better safety than gene delivery approaches [ 33 ]. Ideally, stem cell-based strategies in bone tissue engineering will need the stem cells from both the donor and the host to differentiate into osteoblasts, secrete collagen I and other organic bone matrix components, and then mineralize to form fully functional bone.…”

Harnessing filamentous phages for enhanced stroke recovery

“…This, in turn, provides invaluable insights into potential NDD therapies. Additionally, Mao’s laboratory has explored the use of bacteriophages and peptides as biofunctional materials, as demonstrated in the work of ( 103 ). Using bacteriophage display techniques, they successfully fused gene sequences from two distinct peptides.…”

Silk Protein-Mediated Biomineralization: From Bioinspired Strategies and Advanced Functions to Biomedical Applications

“…Silk protein is a naturally occurring, animal-derived protein, and it is a continuous, long fiber secreted by spiders or mature silkworms during their life activities. − In mulberry silkworm cocoons, the protein content is approximately 97%, consisting of silk fibroin (SF) and silk sericin (SS). Numerous excellent research studies and reviews have delved into the structural characteristics of silk proteins and their applications in various fields, including tissue engineering, − drug delivery systems, smart wearables, sensing, and others. , As shown in Figure , both silk proteins and collagen are structural proteins, that contain significant amounts of polar amino acids. Additionally, both proteins are regularly oriented fibrous structures that are formed by the hierarchical assembly of nanofibrils.…”