Supramolecular design of self-assembling nanofibers for cartilage regeneration

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.self-assembling biomaterials | chondral defects | microfracture | peptide amphiphiles | transforming growth factor

Moving from static to dynamic complexity in hydrogel design

“…This has been difficult for natural materials, where many cues (for example, adhesive and mechanical) are coupled, yet synthetic hydrogels have provided a well-defined platform for experimentation. A variety of biochemical signals have been explored upon or within hydrogels, taking advantage of hydrogels as 'blank slates' that can be decorated with cell-interactive 4 , or growth factor-binding [5][6][7] , ligands. Hydrogels are also useful because their physical properties are biomimetic, that is, they can be designed with stiffness ranges and topographical features that are analogous to natural extracellular environments 8 .…”

“…Approaches such as directed evolution will allow the rapid assessment of sequences with specific functionality. As an alternative to covalently crosslinked structures, hydrogels may be formed via the self-assembly of peptides designed to form fibrillar structures or even to present biological signals 6 . The same cues for adhesion and degradation can be incorporated into such structures 62 , and because selfassembling hydrogels are amenable to modular design, it is possible to optimize these hydrogels for a particular outcome such as endothelialization 63 .…”

“…87). In other circumstances, sequestering may result in local amplification of signals that promote healing by 'harnessing' endogenous, cell-secreted growth factors 6,88,89 . Harnessing of endogenous factors may lead to a series of practical advantages when compared with delivery of purified recombinant factors.…”

Peptide hormones and lipopeptides: from self‐assembly to therapeutic applications

“…They can then be metabolised into lipids and amino acids, which are then easily cleared by the kidneys 19. In therapeutic applications, the hydrophobic tail assists transport across the cell membrane, and the peptide epitope can then be used to target a specific cell via a ligand‐receptor complex 20.…”

Preparation of a novel composite nanofiber gel-encapsulated human placental extract through layer-by-layer self-assembly

“…In the present study, the aqueous HPE was encapsulated in a novel nanocomposite gel fiber (16,17) prepared by the ideal formulation of IKVAV, RGD, RAD16 and FGL-PA through LbL self-assembly (17,18,19,20), and the morphology, particle size, drug loading, drug release efficacy, encapsulation rate and structure validation were examined. IKVAV is an amphiphilic molecule, also known as isoleucine-lysine-valine-alanin-valine.…”