Elastin-like polypeptide modified silk fibroin porous scaffold promotes osteochondral repair

Abstract

Silk fibroin (SF) is considered biocompatible and biodegradable for osteochondral repair. However, it lacks a bioactive domain for cell adhesion, proliferation and differentiation, limiting its therapeutic efficacy. To revamp SF as a biomimicking and bioactive microenvironment to regulate cell behaviours, we engineered an elastin-like polypeptide (ELP, Val-Pro-Gly-Xaa-Gly) to modify SF fibers via simple and green dehydrothermal (DHT) treatment. Our results demonstrated that the ELP successfully bound to SF, and the scaffold was reinforced by the fusion of the silk fiber intersections with ELP (S-ELP-DHT) via the DHT treatment. Both bone mesenchymal stem cells (BMSCs) and chondrocytes exhibited improved spreading and proliferation on the S-ELP-DHT scaffolds. The ex vivo and in vivo experiments further demonstrated enhanced mature bone and cartilage tissue formation using the S-ELP-DHT scaffolds compared to the naked SF scaffolds. These results indicated that a recombinant ELP-modified silk scaffold can mimic three-dimensional (3D) cell microenvironment, and improve bone and cartilage regeneration. We envision that our scaffolds have huge clinical potential for osteochondral repair.

Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration

“…Another novel strategy to improve the cell adhesion, proliferation and differentiation into SF scaffold is the adhesion of an elastin-like polypeptide (ELP, Val-Pro-Gly-Xaa-Gly) [ 69 ] via simple and green dehydrothermal (DHT) treatment, which represents an environment-friendly strategy and possesses high reproducibility [ 70 , 71 ]. Chen and coworkers demonstrated that bone marrow-derived MSCs (BM-MSCs) exhibited not only improved spreading and proliferation on the SF-ELP-DHT scaffolds, but also showed enhanced mature bone tissue formation compared to the naked SF scaffolds [ 72 ]. These results pointed out recombinant ELP modified silk scaffold as a promising candidate material for bone regeneration, given that it could mimic the required bone 3-dimensional (3D) microenvironment.…”

Graphene–Oxide Porous Biopolymer Hybrids Enhance In Vitro Osteogenic Differentiation and Promote Ectopic Osteogenesis In Vivo

“…Interestingly, studies have observed that the implantation of a scaffold engineered for BTE purposes at an ectopic site still has the means to recruit bone cells and to generate bone tissue, even if not surrounded by it [ 34 ]. Exquisite studies reported the implantation of BTE-designed scaffolds in other areas (e.g., subcutaneously/in muscle) in order to prove the osteoinductive and osteoconductive properties of the scaffolds [ 35 , 36 , 37 , 38 ]. These unique events have been proven for biomaterials such as β-tricalcium phosphate scaffolds [ 39 ], hydroxyapatite-based materials [ 40 ] and also phosphate graphene composites [ 41 ].…”

Immune Response to Silk Sericin–Fibroin Composites: Potential Immunogenic Elements and Alternatives for Immunomodulation

“…[145] With these limitations in mind, some studies have been carried out to improve the mechanical properties of SF, [146] while others focused on increasing its bioactivity for bone regeneration. [140,143,147] It has thus been demonstrated that silica nanoparticles dispersed in silk fibroin nanofibers led to superior osteoinduction ability and better mechanical properties as compared with SF hydrogels. [146] It has also been shown that the incorporation of rosuvastatin, [140] bioactive glass, [143] and hydrogen sulfide [148] in SF scaffolds can improve cell proliferation and induce osteogenic differentiation.…”