Functionalized silk-based biomaterials for bone formation

TLDR

Silks are being reassessed as biomaterial scaffolds because of their unique mechanical properties, genetic tailoring potential, and confirmed biocompatibility. The study aims to covalently decorate silk films with integrin‑recognition sequences (RGD) and parathyroid hormone peptides (PTH, 1‑34 and a modified form) to promote bone formation. The authors covalently attach RGD, PTH, and modified PTH to silk films, creating functionalized biomaterial matrices. RGD‑functionalized silk markedly increases osteoblast adhesion, alkaline phosphatase, procollagen, osteocalcin expression, and calcification, demonstrating enhanced in‑vitro mineralization.

Abstract

Silks are being reassessed as biomaterial scaffolds due to their unique mechanical properties, opportunities for genetic tailoring of structure and thus function, and recent studies clarifying biocompatibility. We report on the covalent decoration of silk films with integrin recognition sequences (RGD) as well as parathyroid hormone (PTH, 1-34 amino acids) and a modified PTH 1-34 (mPTH) involved in the induction of bone formation. Osteoblast-like cell (Saos-2) responses to the decorated silk films indicate that the proteins serve as suitable bone-inducing matrices. Osteoblast-like cell adhesion was significantly increased on RGD and PTH compared to plastic, mPTH, and the control peptide RAD. At 2 weeks of culture, message levels of alkaline phosphatase were similar on all substrates, but by 4 weeks, alkaline phosphatase mRNA was greatest on RGD. At 2 weeks of culture, alpha 1(I) procollagen mRNA was elevated on silk, RGD, RAD, and PTH, and hardly detectable on mPTH and plastic. However, by 4 weeks RGD demonstrated the highest level compared to the other substrates. Osteocalcin message levels detected by RT-PCR were greatest on RGD at both time points. Calcification was also significantly elevated on RGD compared to the other substrates with an increase in number and size of the mineralized nodules in culture. Thus, RGD covalently decorated silk appears to stimulate osteoblast-based mineralization in vitro.