Protein and cell therapies are limited by delivery methods

Protein and cell therapies represent promising strategies for various regenerative medicine therapies. However, these therapies are significantly limited by delivery methods, particularly in terms of protein stability and dosing kinetics as well as cell survival, engraftment, and function. Hydrogels represent versatile and robust delivery vehicles for proteins and cells due to their high water content that aids protein biological activity, high cytocompatibility, and minimal adverse host reactions. However, current hydrogel technologies degrade too slowly for many applications.

Novel hydrogels aid in tunable degradation kinetics

Georgia Tech scientists engineered a hydrolytically degradable poly(ethylene glycol) (PEG) hydrogel technology for numerous in vitro and in vivo applications. The PEG macromer uses ester linkages embedded in the PEG backbone (4-arm PEG-ester-maleimide), which can be combined at various ratios with non-degradable macromers to enable tunable degradation kinetics. The hydrogel material enables tight control over gel degradation and therapeutic release kinetics. This technology overcomes limitations of widely use hydrogels crosslinked with protease-degradable linkers that exhibit slow and site-dependent degradation rates.

Applications for this technology include controlled release and delivery of drugs or proteins as well as cell encapsulation. In addition, it can be used as a delivery vehicle and adhesive for cells in transplantation settings, as current data promotes human stem cell viability and engraftment in vivo.

Solution Advantages
  • Improved viability: Promotes cell vascularization, encapsulation, and transplantation
  • Customizable: Offers tunable degradation kinetics in vitro and in vivo in a wide variety of animal models and transplant sites
  • Supports regenerative medicine: Allows for rapid hydrolytic cleavage in the in vivo environment but remains stable in vitro for weeks at neutral pH 7 
Potential Commercial Applications
  • Tissue engineering
  • Drug delivery
  • Regenerative medical therapies
  • Research tool for biotechnology applications
An example hydrogel delivery system:  VEGF + PEG-4MAL leads to PEGylated-VEGF which leads (via SH degradable crosslinker) to crosslinked degradable VEGF-PEG-4MAL hydrogel which leads (via protease) to degradation products.

Example hydrogel delivery system employing PEG-VPM hydrogels