Designer D-form self-assembling peptide scaffolds promote the proliferation and migration of rat bone marrow-derived mesenchymal stem cells

Abstract

Self-assembling peptide (SAP) nanofiber hydrogel scaffolds have become increasingly important in tissue engineering due to their outstanding bioactivity and biodegradability. However, there is an initial concern on their long-term clinical use, since SAPs made of L-form amino acid sequences are sensitive to enzymatic degradation. In this study, we present a designer SAP, D-RADA16, made of all D-amino acid. We investigated the nanofiber morphology of D-RADA16, its potential for the culture of bone marrow-derived mesenchymal stem cells (BMSCs), and the proteolytic resistance of the biomaterial. The results revealed that D-RADA16 exhibited stable β-sheets and formed interwoven nanofiber scaffolds in water. D-RADA16 and L-RADA16 hydrogel scaffolds were both found to promote the proliferation and migration of rat BMSCs in the 3D cell culture microenvironment. Furthermore, the D-RADA16 scaffolds exhibited a higher proteolytic resistance against proteinase K than the L-RADA16 scaffolds. These observations indicate that D-RADA16 hydrogel scaffolds have excellent bioactivity, biocompatibility and biostability, and thus may serve as promising candidates for long-term application in vivo.

<p>Delivery of MSCs with a Hybrid β-Sheet Peptide Hydrogel Consisting IGF-1C Domain and D-Form Peptide for Acute Kidney Injury Therapy</p>

“…47 Accumulating studies have demonstrated that peptides made of only D-form amino acids are more resistant to protease degradation compared with their L-form counterparts, thus, self-assembling peptides with D-form amino acids are highly durable and seem to be a tangible option for improved scaffold stability. 30,31,40 Hydrogel without functional motif is not sufficient to mimic all the properties of ECM in vivo due to the complex relationship between structure and biophysical functions. The morphology provides only an architectural support and a physiochemical signal but lacks an inherent biological motif.…”

“…To resist natural enzyme degradation, D-form self-assembling peptide nanofiber scaffolds have been used for cell culture and tissue regeneration. 2,30,39,40 IGF-1 mediates cell growth and differentiation and has been widely used in tissue engineering and regenerative medicine. 17,41 Therefore, the design of biomimetic scaffolds with bioactivity-mimicking peptide IGF-1C and D-form self-assembling peptide motif Nap-FFG was developed.…”

“…[26][27][28][29] A recent study revealed that self-assembling peptide hydrogels with β-sheet structures, made of D-amino acids, exhibit high resistance against enzymatic hydrolysis. 30 The conjugation of bioactivity-mimicking peptides to the backbone of self-assembling β-sheets derived from D-amino acids may result in improved biostability and bioactivity for potential therapeutic applications. 28,30,31 This solution may provide a more effective way to generate hydrogel scaffolds for stem cells in regenerative medicine.…”

“…30 The conjugation of bioactivity-mimicking peptides to the backbone of self-assembling β-sheets derived from D-amino acids may result in improved biostability and bioactivity for potential therapeutic applications. 28,30,31 This solution may provide a more effective way to generate hydrogel scaffolds for stem cells in regenerative medicine.…”

Amphiphilic peptides as novel nanomaterials: design, self-assembly and application

“…Furthermore, with the recent development of biotechnology, genetic engineering, synthetic and material chemistry, de novo designer self-assembling molecules have also been developed rapidly. [4][5][6][7][8][9][10][11] These novel self-assembling molecules, biomimetically derived or de novo designed, have shown great potential as nanomaterials in a wide range of fields including regenerative medicine, [12][13][14][15][16][17][18] cancer research, [19][20][21] three-dimensional (3-D) cell culture, [22][23][24][25][26][27][28][29] drug and gene delivery, [30][31][32][33][34][35][36][37][38][39] nanotechnology [40][41][42] and so on.…”