The
potential to control the rate of replacement of a biodegradable
implant by a tissue would be advantageous. Here, we demonstrate that
tissue invasion can be tuned through the novel approach of overlaying
an enzymatically degradable hydrogel with an increasingly hydrolytically
degradable environment. Poly(ethylene glycol) (PEG) hydrogels were
formed from varying proportions of PEG-vinyl sulfone and PEG-acrylate
(PEG-AC) monomers via a Michael-type addition reaction with a dithiol-containing
matrix-metalloproteinase-susceptible peptide cross-linker. Swelling
studies showed that PEG hydrogels with similar initial stiffnesses
degraded more rapidly as the PEG-AC content increased. The replacement
of subcutaneously implanted PEG hydrogels was also found to be proportional
to their PEG-AC content. In addition, it would in many instances be
desirable that these materials have the ability to stimulate their
neovascularization. These hydrogels contained covalently bound heparin,
and it was shown that a formulation of the hydrogel that allowed tissue
replacement to occur over 1 month could trap and release growth factors
and increase neovascularization by 50% over that time.
Directed cell motility, as controlled by soluble factors, is crucial for many biological processes, including development, cancer progression, and wound healing. The use of directed cell motility also shows promise for applications in regenerative medicine such as therapeutic angiogenesis. Unfortunately, current in vitro 3-D migration and invasion models limit our understanding and application of these processes. Here, we present a novel and cost-effective 3-D chemotaxis assay for assessing the invasive response of cells to a chemoattractant extracellular matrix (ECM). Our system takes advantage of a custom-casting chamber to set two gels in contact with each other along a defined front, one containing a suitable chemoattractant and the other the cells. Rotation of the chamber allows easy visualization of invasion across the interface. The effectiveness of the assay was demonstrated by studying the invasion of both human dermal fibroblasts (FBs) and smooth muscle cells (SMCs) into a polyethylene glycol (PEG) hydrogel containing basic fibroblast growth factor (bFGF). Incorporation of bFGF resulted in significantly increased and directional invasion for both cell groups.
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