Hydrogels for Local Delivery of Therapeutics

Figure 1. Schematic depicting a hydrogel formulated for delivery of a peptide therapeutic by enzymatic degradation.
This hydrogel is composed of 8-arm poly(ethylene glycol) (PEG)-norbornene, matrix metalloproteinase (MMP)-degradable
crosslinkers, and MMP-degradable tethers bound to the therapeutic of interest. Cell-secreted MMPs degrade the gel network
and tethers, releasing the therapeutic molecule.

Project Collaborators: Dr. Hani Awad

Hydrogels can be exploited to encapsulate and deliver cells and biomolecules therapeutically, as delivery characteristics can be intimately controlled through alterations in hydrogel biophysical and biochemical structure. We use poly(ethylene glycol) (PEG) hydrogels as local delivery systems for cells and/or therapeutics that act locally to aid tissue regeneration in several applications, including ischemic tissue disorders, fractures, and critical-size bone defects.

We hypothesize that hydrogels designed to encapsulate cells and control the availability of cellularly-released paracrine factors and/or other therapeutic molecules such as growth factors, gene vectors, or small interfering RNA, will be useful for these therapeutic strategies. Our highly tunable PEG hydrogel platform can encapsulate soluble factors for diffusion-controlled release and/or support cell-mediated release by covalent conjugation of therapeutics via enzymatically degradable linkers. For example, peptide mimetics of growth factors, such as NGF or VEGF, can be tethered to the polymer using matrix metalloproteinase (MMP)-cleavable linkers to create cell-responsive delivery systems (Figure 1).