Supramolecular design of self-assembling nanofibers for cartilage regeneration

TLDR

Molecular and supramolecular design of bioactive biomaterials could significantly impact regenerative medicine, especially by enabling minimally invasive, self‑assembling injectable liquids that solidify into bioactive structures in tissue. The study reports a coassembly system of peptide amphiphile molecules that form nanofibers for cartilage regeneration by presenting high‑density TGFβ‑1 binding epitopes. The coassembly system uses peptide amphiphiles that self‑assemble into nanofibers, incorporating TGFβ‑1 binding sites to enable controlled growth factor presentation. Passive TGFβ‑1 release from PA gels was slower, and the materials supported human mesenchymal stem cell survival and chondrogenic differentiation in vitro; in a rabbit full‑thickness chondral defect model, the materials promoted cartilage regeneration with or without exogenous growth factor, demonstrating the potential of a synthetic bioactive biomaterial for cartilage repair.

Abstract

Molecular and supramolecular design of bioactive biomaterials could have a significant impact on regenerative medicine. Ideal regenerative therapies should be minimally invasive, and thus the notion of self-assembling biomaterials programmed to transform from injectable liquids to solid bioactive structures in tissue is highly attractive for clinical translation. We report here on a coassembly system of peptide amphiphile (PA) molecules designed to form nanofibers for cartilage regeneration by displaying a high density of binding epitopes to transforming growth factor β-1 (TGFβ-1). Growth factor release studies showed that passive release of TGFβ-1 was slower from PA gels containing the growth factor binding sites. In vitro experiments indicate these materials support the survival and promote the chondrogenic differentiation of human mesenchymal stem cells. We also show that these materials can promote regeneration of articular cartilage in a full thickness chondral defect treated with microfracture in a rabbit model with or even without the addition of exogenous growth factor. These results demonstrate the potential of a completely synthetic bioactive biomaterial as a therapy to promote cartilage regeneration.