On the design and efficacy assessment of self-assembling peptide-based hydrogel-glycosaminoglycan mixtures for potential repair of early stage cartilage degeneration.

Peptide-based hydrogels are of interest for their potential use in regenerative medicine. Combining these hydrogels with materials that may enhance their physical and biological properties, such as glycosaminoglycans, has the potential to extend their range of biomedical applications, for example in the repair of early cartilage degeneration. The aim of this study was to combine three self-assembling peptides (P11 -4, P11 -8, and P11 -12) with chondroitin sulphate at two molar ratios of 1:16 and 1:64 in 130 and 230 mM Na+ salt concentrations. The study investigates the effects of mixing self-assembling peptide and glycosaminoglycan on the physical and mechanical properties at 37°C. Peptide alone, chondroitin sulphate alone, and peptide in combination with chondroitin sulphate were analysed using Fourier transform infrared spectroscopy to determine the ß-sheet percentage, transmission electron microscopy to determine the fibril morphology, and rheology to determine the elastic and viscous modulus of the materials. All of the variables (peptide, salt concentration, and chondroitin sulphate molar ratio) had an effect on the mechanical properties, ß-sheet formation, and fibril morphology of the hydrogels. P11 -4 and P11 -8-chondroitin sulphate mixtures, at both molar ratios, were shown to have a high ß-sheet percentage, dense entangled fibrillar networks, as well as high mechanical stiffness in both (130 and 230 mM) Na+ salt solutions when compared with the P11 -12/chondroitin sulphate mixtures. These peptide/chondroitin sulphate hydrogels show promise for biomedical applications in glycosaminoglycan depleted tissues.

Treatment of early caries lesions using biomimetic self-assembling peptides--a clinical safety trial.

OBJECTIVE: We previously reported that a rationally designed biomimetic self-assembling peptide, P11-4, nucleated hydroxyapatite de novo and was apparently capable of in situ enamel regeneration following infiltration into caries-like lesions. Our present aim was to determine the safety and potential clinical efficacy of a single application of P11-4 on early enamel lesions. MATERIALS AND METHODS: Fifteen healthy adults with Class V 'white spot' lesions received a single application of P11-4. Adverse events and lesion appearances were recorded over 180 days. RESULTS: Patients treated with P11-4 experienced a total of 11 adverse events during the study, of which two were possibly related to the protocol. Efficacy evaluation suggested that treatment with P11-4 significantly decreased lesion size (p = 0.02) after 30 days and shifted the apparent progression of the lesions from 'arrested/progressing' to 'remineralising' (p <0.001). A highly significant improvement in the global impression of change was recorded at day 30 compared with baseline (p <0.001). CONCLUSIONS: The results suggest that treatment of early caries lesions with P11-4 is safe, and that a single application is associated with significant enamel regeneration, presumably by promoting mineral deposition within the subsurface tissue.

Peptide synthesis and self-assembly.

Peptides and proteins are the most diverse building blocks in biomolecular self-assembly in terms of chemistry, nanostructure formation and functionality. Self-assembly is an intrinsic property of peptides. In this chapter, we attempt to address the following issues: How can we synthesize a self-assembling peptide? What are the fundamental physical and chemical principles that underpin peptide self-assembly? How can we learn to finely control peptide self-assembly? The merits of answering these questions are inspiring both for biology and medicine in terms of new opportunities for understanding, preventing and curing of diseases, and for nanotechnology in terms of new prescribed routes to achieving peptide-based nanostructures with a range of properties appropriate for specific applications.