Enzymatically Cross-linked Hydrogels Based on Synthetic Poly(α-amino acid)s Functionalized with RGD Peptide for 3D Mesenchymal Stem Cell Culture

Abstract

Injectable hydrogel scaffolds combined with stem cell therapy represent a promising approach for minimally invasive surgical tissue repair. In this study, we developed and characterized a fully synthetic, biodegradable poly(N 5 -(2-hydroxyethyl)-L-glutamine)-based injectable hydrogel modified with integrin-binding arginine−glycine−aspartic acid (RGD) peptide (PHEG-Tyr-RGD). The biodegradable hydroxyphenyl polymer precursor derivative of PHEG-Tyr was enzymatically cross-linked to obtain injectable hydrogels with different physicochemical properties. The gelation time, gel yield, swelling behavior, and storage modulus of the PHEG-Tyr hydrogels were tuned by varying the concentrations of the PHEG-Tyr precursors and horseradish peroxidase as well as the n H 2 O 2 /n Tyr ratio. The mechanical properties and gelation time of the PHEG-Tyr hydrogel were optimized for the encapsulation of rat mesenchymal stem cells (rMSCs). We focused on the 2D and 3D spreading and viability of rMSCs within the PHEG-Tyr-RGD hydrogels with different physicochemical microenvironments in vitro. Encapsulation of rMSCs shows long-term survival and exhibits cell−matrix and cell−cell interactions reflective of both the RGD concentration and hydrogel stiffness. The presented biomaterial represents a suitable biological microenvironment to guide 3D spreading and may act as a promising 3D artificial extracellular matrix for stem cell therapy.

Gram-selective antibacterial peptide hydrogels

“…Peptide hydrogels, which are three-dimensional networks of self-assembled peptide supramolecular structures that hold large amounts of water, have shown good biocompatibility, biofunctional diversity, and responsiveness. [37][38][39][40] These features have endowed peptide hydrogels with great potential in various biomedical applications involving cell therapy, 40,41 drug delivery, [42][43][44][45] tissue engineering and regeneration, [45][46][47][48][49] biosensors, 50,51 and wound healing. [52][53][54][55][56] Excellent antimicrobial activities have been achieved by hydrogels selfassembled by AMPs without loading them with additional antimicrobial drugs.…”

Histidine-Containing Amphiphilic Peptide-Based Non-Cytotoxic Hydrogelator with Antibacterial Activity and Sustainable Drug Release

“…This kind of soft material being easily useable, nontoxic, biocompatible, and biodegradable has extensive applications in biomedical technology as well as in environmental science. The tunable property of the hydrogel through various stimuli such as pH, mechano-responsiveness, chemo-responsiveness, light, heat, and others make them suitable as carriers of numerous drugs and biomolecules. , Confinement of a large volume of water into a 3D-hydrogel network enables them to mimic biological systems and thus hydrogels have beneficial applications in tissue engineering, , cell culture, , tissue regeneration, antibacterials, , wound healing, or cell adhesion and proliferation. , Hydrogels have also been used for environmental remediation by removing toxic organic dyes, heavy metals, , and oil spills. ,, Apart from this, a notable property of hydrogel is its thixotropic ,, nature in which a gel–sol–gel transition occurs. By applying a mechanical shear strain/stress a gel can be broken and turned into solution and this can reform when the applied force is withdrawn.…”

“…The tunable property of the hydrogel through various stimuli such as pH, mechano-responsiveness, chemo-responsiveness, light, heat, and others make them suitable as carriers of numerous drugs and biomolecules. 18,19 Confinement of a large volume of water into a 3D-hydrogel network enables them to mimic biological systems and thus hydrogels have beneficial applications in tissue engineering, 20,21 cell culture, 22,23 tissue regeneration, 24 antibacterials, 25,26 wound healing, 27 or cell adhesion and proliferation. 28,29 Hydrogels have also been used for environmental remediation by removing toxic organic dyes, 30 heavy metals, 30,31 and oil spills.…”

Tailored Polypeptide Star Copolymers for 3D Printing of Bacterial Composites Via Direct Ink Writing

“…For example, polypeptides offer tailored molecular weights, controlled secondary structures, [ 31 ] degradable backbones and functional side chains [ 32 ] for modulating physicochemical, biofunctional and mechanical properties. [ 33–35 ] As a result, the exploration of polypeptides hydrogels as 3D printable bioinks may offer significant potential for the 3D printing of bacteria‐based biocomposites ( Figure ).…”