Growth‐Factor Free Multicomponent Nanocomposite Hydrogels That Stimulate Bone Formation

Abstract

Synthetic osteo‐promoting materials that are able to stimulate and accelerate bone formation without the addition of exogenous cells or growth factors represent a major opportunity for an aging world population. A co‐assembling system that integrates hyaluronic acid tyramine (HA‐Tyr), bioactive peptide amphiphiles (GHK‐Cu2+), and Laponite (Lap) to engineer hydrogels with physical, mechanical, and biomolecular signals that can be tuned to enhance bone regeneration is reported. The central design element of the multicomponent hydrogels is the integration of self‐assembly and enzyme‐mediated oxidative coupling to optimize structure and mechanical properties in combination with the incorporation of an osteo‐ and angio‐promoting segments to facilitate signaling. Spectroscopic techniques are used to confirm the interplay of orthogonal covalent and supramolecular interactions in multicomponent hydrogel formation. Furthermore, physico‐mechanical characterizations reveal that the multicomponent hydrogels exhibit improved compressive strength, stress relaxation profile, low swelling ratio, and retarded enzymatic degradation compared to the single component hydrogels. Applicability is validated in vitro using human mesenchymal stem cells and human umbilical vein endothelial cells, and in vivo using a rabbit maxillary sinus floor reconstruction model. Animals treated with the HA‐Tyr‐HA‐Tyr‐GHK‐Cu2+ hydrogels exhibit significantly enhanced bone formation relative to controls including the commercially available Bio‐Oss.

The Overview of Porous, Bioactive Scaffolds as Instructive Biomaterials for Tissue Regeneration and Their Clinical Translation

“…The chosen peptide sequence contributed to high water retention and stimulated the formation of blood vessels. Moreover, the gel was injectable, which avoids any extensive surgery [ 220 ].…”

The role of lithium in the osteogenic bioactivity of clay nanoparticles

“…Paper effect of LAPONITE® on osteogenic differentiation of skeletal populations has been widely reported [1][2][3][31][32][33][34][35][36] and observed both when applied as a dispersed additive to cell culture media 2,3,31,32 and as a composite in polymeric biomaterials. 5,[33][34][35][36] In discussions of potential mechanisms in the literature it is frequently suggested that nanoclay bioactivity could be attributed to LAPONITE® degradation products. [2][3][4][5][6][7][8]31 Lithium is of particular interest in this context for its well-established pharmacological action as an agonist of the canonical Wnt pathway.…”

“…LAPONITE® nanoparticle addition caused a pronounced enhancement in ALP activity, calcium deposition and ALPL and COL1A1 gene expression in agreement with previous studies. [1][2][3]5,[31][32][33][34][35][36] Interestingly, genes for the principle osteogenic transcription factors, Runx2 and Osterix (SP7), were not upregulated in response to LAPONITE®, suggesting alternative signaling pathways lie behind the phenotypic changes observed. This observation is in contrast with some previous studies which describe upregulation of Runx2 with LAPONITE® addition, 2,3,32 although, notably, a whole transcriptome analysis of LAPONITE® effects on HBMSCs also recorded neither gene as being differentially expressed under similar conditions (RUNX2, false-discovery rate-adjusted P = 0.519 as calculated by authors from source dataset; SP7, undetermined).…”

Folding and self-assembly of short intrinsically disordered peptides and protein regions

“…11 Peptide derivatives are also relevant when considering biomineralization at interfaces. 12,13 Peptides can form hybrids with relevant nanostructures based on carbon for subsequent self-assembly into intriguing materials. 14,15 The structural features of proteins and peptide fragments are undoubtedly the focus of a large body of research.…”