Osteogenic Differentiation of Human Mesenchymal Stem Cells Directed by Extracellular Matrix-Mimicking Ligands in a Biomimetic Self-Assembled Peptide Amphiphile Nanomatrix

Abstract

This study investigated the ability of nanoscale, biomimetic peptide amphiphile (PA) scaffolds inscribed with specific cellular adhesive ligands to direct the osteogenic differentiation of human mesenchymal stem cells (hMSCs) without osteogenic supplements. PA sequences were synthesized to mimic the native bone extracellular matrix (ECM), expressing different isolated ligands (i.e. RGDS, DGEA, KRSR). All PAs were presented as self-assembled two-dimensional coatings for the seeded hMSCs. Initial attachment results demonstrated that the different PAs could be individually recognized based on the incorporated adhesive ligands. Long-term studies assessed osteogenic differentiation up to 35 days. The RGDS-containing PA nanomatrix expressed significantly greater alkaline phosphatase (ALP) activity, indicating the early promotion of osteogenic differentiation. A progressive shift towards osteogenic morphology and positive staining for mineral deposition provided further confirmation of the RGDS-containing PA nanomatrix. Overall, the PA nanomatrix clearly has great promise for directing the osteogenic differentiation of hMSCs without the aid of supplements by mimicking the native ECM, providing an adaptable environment that allows for different adhesive ligands to control cellular behaviors. This research model establishes the beginnings of a new versatile approach to regenerate bone tissues by closely following the principles of natural tissue formation.

Peptide Amphiphile Micelles Self-Adjuvant Group A Streptococcal Vaccination

“…They have been shown capable of delivering biologically active peptides for a variety of applications including angiogenesis (19,20), osteogenesis (21,22), neurogenesis (23,24), atherosclerosis treatment (25), cancer therapy (26,27), and islet transplantation (28,29). Also, peptide amphiphile micelles are comprised of a high concentration of peptide (30), inhibit peptide degradation (31), and can greatly increase peptide intracellular delivery (32).…”

A Comprehensive Review on the Role of Various Materials in the Osteogenic Differentiation of Mesenchymal Stem Cells with a Special Focus on the Association of Heat Shock Proteins and Nanoparticles

“…The self-assembling PA nanomatrix promotes osteogenic differentiation of hMSCs without the aid of supplements by providing a native bone ECM [Anderson et al, 2009]. PA assembled into nanofibers and phosphoserine residues were incorporated into the peptide sequence to improve its bioactivity, which promotes hydroxyapatite formation in the culture [Sargeant et al, 2012].…”

Advances in Regenerative Medicine

“…Therefore a biofunctionalization of a scaffold surface should not focus on the presentation of a uniform coating to engage a single receptor, but rather identify the properties that control the presentation of integrin-specific epitopes within the coatings (Keselowsky, Collard et al 2005). Clearly several additional chemical modifications can be introduced and applied to almost any specific substrata, provided that the proper chemistry is used; indeed many strategies and approaches are currently being tested (Fu, Wang et al 2011), ranging from simple coatings onto specific substrates (Uygun, Stojsih et al 2009), to the contemporary use of genetic engineering and structural approaches (Benoit, Schwartz et al 2008;Gorsline, Tangkawattana et al 2010), to combinations of matrix-mimicking ligands and engineered structured nanomatrices (Anderson, Kushwaha et al 2009). The same natural extracellular matrix is per se able to induce specific cell commitment (Chen, Dusevich et al 2007).…”