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Development of a Novel Matrix Metalloproteinase‐Inhibiting Wound Dressing
Author(s) -
Skarja Gary A.,
Gorbet Maud B.,
LawsonSmith Rebecca K.,
May Michael H.,
Sefton Michael V.
Publication year - 2004
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2004.0abstractg.x
Subject(s) - gelatin , collagenase , matrix metalloproteinase , in vivo , wound healing , chemistry , in vitro , extracellular matrix , glutaraldehyde , zymography , matrix (chemical analysis) , biomedical engineering , biochemistry , chromatography , surgery , medicine , enzyme , biology , microbiology and biotechnology
Rimon Therapeutics develops synthetic therapeutic polymers (Theramers™) that combine bioactivity with a broad range of desirable mechanical and physical properties. The MI Theramer™ is a polymer that modulates the activity of matrix metalloproteinases (MMPs).. Excessive proteolytic cleavage of extracellular matrix and growth factors resulting from elevated levels of MMPs is believed to contribute to the impaired wound healing associated with chronic, non‐healing wounds. MI Theramer™ beads suspended in ThermaGel™(a thermoreversible gel) make up MI‐Gel™ Dressing. The dressing may be applied as a liquid that is poured into a wound, where it will gel on contact. The dressing can be reliquified and removed easily without re‐injuring the wound by cooling it. In vitro inhibition of collagenase type IV (equivalent to MMP‐2) from clostridium histolyticum (Molecular Probes) was measured. A dose‐dependent inhibition of MMP‐2 activity was measured for MI Theramer™ beads alone and suspended in ThermaGel™ indicating that MMP‐2 is able to diffuse into the gel and bind to the beads suspended therein. In vivo efficacy was demonstrated by observing the degradation of glutaraldehyde cross‐linked gelatin tubes using a mouse subcutaneous pouch model. Gelatin zymography on extracts collected from the gelatin tubes co‐implanted with MI Theramer™ beads also showed reduced MMP‐2 and MMP‐9 activity in comparison to controls. The insoluble MI Theramer™ beads were able to modulate MMP activity both in vitro and in vivo . The beads retained their inhibitory activity when they were suspended in a novel thermoreversible gel (ThermaGel™). The combined MI‐Gel™ Dressing may have promise as a novel chronic wound healing product.