Protease-sensitive PEG hydrogels regulate vascularization in vitro and in vivo.

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Forming functional blood vessel networks is crucial for engineered and ischemic tissues.
• Poly(ethylene glycol) (PEG)-based hydrogels offer tunable properties to study vascularization.
• Understanding the impact of mechanical properties and proteolytic degradation on vascularization is key.

Purpose of the Study:

• To investigate the role of hydrogel crosslinking and matrix metalloproteinase (MMP) susceptibility on vascular network formation.
• To evaluate the efficacy of PEG-based hydrogels in supporting vascularization both in vitro and in vivo.

Main Methods:

• Synthesis of four-arm PEG vinyl sulfone hydrogels crosslinked with peptides of varying MMP cleavage rates.
• Co-encapsulation of endothelial cells and fibroblasts within hydrogels.
• Assessment of vascular morphogenesis in vitro and vascularization following in vivo transplantation.

Main Results:

• In vitro vascular morphogenesis was robust to peptide identity but attenuated by increased crosslinking and MMP inhibition.
• In vivo, perfused vasculature formed in all gel types.
• Vascularization in vivo was not decreased by increased crosslinking, contrasting with in vitro findings.

Conclusions:

• PEG-based hydrogel platform effectively supports vascularization in vitro and in vivo.
• Hydrogel crosslinking density and proteolytic susceptibility differentially impact vascularization depending on the environment (in vitro vs. in vivo).
• This platform provides a valuable tool for studying and promoting vascularization in tissue engineering and regenerative medicine.