RGD-Hydrogel Improves the Therapeutic Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Phosgene-Induced Acute Lung Injury in Rats

Abstract

Mesenchymal stem cells (MSCs) have promising potential in the treatment of various diseases, such as the therapeutic effect of bone marrow-derived MSCs for phosgene-induced acute lung injury (P-ALI). However, MSC-related therapeutics are limited due to poor cell survival, requiring appropriate MSC delivery systems to maximise therapeutic capacity. Biomaterial RGD-hydrogel is a potential cell delivery vehicle as it can mimic the natural extracellular matrix and provide cell adhesion support. The application of RGD-hydrogel in the MSC treatment of respiratory diseases is scarce. This study reports that RGD-hydrogel has good biocompatibility and can increase the secretion of Angiopoietin-1, hepatocyte growth factor, epidermal growth factor, vascular endothelial cell growth factor, and interleukin-10 in vitro MSCs. The hydrogel-encapsulated MSCs could further alleviate P-ALI and show better cell survival in vivo. Overall, RGD-hydrogel could improve the MSC treatment of P-ALI by modulating cell survival and reparative activities. It is exciting to see more and more ways to unlock the therapeutic potential of MSCs.

Lung Extracellular Matrix Hydrogels-Derived Vesicles Contribute to Epithelial Lung Repair

“…Regarding cell therapy, hydrogels provide clear advantages to conventional culture. Their biophysical characteristics can be easily adjusted, other external physical stimuli (such as cyclic stretch) can be applied, are used as bioinks for bioprinting, and can be used as vehicle facilitating MSCs engraftment and viability after transplantation [12,13,24]. This work reveals that L-HG is also an important source of bioactive proteins and derived vesicles that can modulate multiple cellular mechanisms.…”

“…Interestingly, MSCs cultured on decellularized lung scaffolds [11] and native lung-derived hydrogels [3] increased their therapeutic potential compared to conventional cell cultures. In a recent study, hydrogel-encapsulated MSCs could further alleviate acute lung injury, increasing the expression of several growth factors and interleukin-10 [12]. In addition, hydrogel-encapsulated MSCs showed better cell survival and could increase their engraftment in the injured tissue [13].…”

Peptide Hydrogels and Nanostructures Controlling Biological Machinery

“…Short peptide sequences have been identified and derived from the ECM to support cell adhesion and growth. These sequences can be incorporated into the material design to promote cell–cell and cell–matrix interactions, which directly influence cell behavior . These materials utilize peptide functionalization to mimic the cellular environment and provide molecular cues to promote tissue regeneration and repair .…”

“…These short peptides are more stable and exhibit less steric hindrance compared to their full-length proteins . The fibronectin-derived cell adhesion sequence arginine-glycine-aspartic acid (RGD) has been demonstrated to promote cell proliferation in vivo and in vitro. , Laminin-derived peptides can be functionalized to induce cell aggregation and adhesion . Laminin-derived peptides include IKVAV, YIGSR, PDSGR, and RYVVLPR .…”

“…These sequences can be incorporated into the material design to promote cell–cell and cell–matrix interactions, which directly influence cell behavior. 23 These materials utilize peptide functionalization to mimic the cellular environment and provide molecular cues to promote tissue regeneration and repair. 24 These short peptides are more stable and exhibit less steric hindrance compared to their full-length proteins.…”