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Thiol-Reactive Crosslinkers for Biomaterials

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41EB004710-01
Agency Tracking Number: EB004710
Amount: $100,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Solicitation Year: N/A
Award Year: 2004
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
United States
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (801) 585-9051
Business Contact
Phone: (801) 232-3603
Research Institution

DESCRIPTION (provided by applicant): A limited number of cytocompatible crosslinkers are available for the preparation of cell-seeded hydrogels and in vivo biocompatible injectable biomaterials. To expand this selection, Sentrx Surgical, Inc. will synthesize and evaluate a series of thiol-reactive bivalent and polyvalent crosslinkers based on polyethylene glycol (PEG). We will determine the relative reactivity of the new linkers with cysteine-containing peptides that would be covalently immobilized to thiol-modified hyaluronan (HA) or chondroitin sulfate (CS) and then crosslinked into a hydrogel. We will also establish the feasibility of using these new crosslinkers as in situ crosslinkable synthetic mimics of the extracellular matrix (ECM) for cell encapsulation in vitro and tissue regeneration in vivo. Specifically, we will explore five specific aims. First, we will synthesize five bivalent and five polyvalent PEG derivatives. Second, we will determine the pH dependence of the rates of reaction of each these linkers with cysteine and with HA-DTPH, a thiol-modified HA with the bivalent crosslinkers; rates will include comparison with known thiol-reactive PEG crosslinkers. Third, we will select three chemistries to prepare CRGDS clusters for attachment and crosslinking to give three new CRGDS-modified HA-DTPH hydrogels. Fourth, these new materials will be evaluated for cytocompatibility and cell growth in vitro with murine fibroblasts. Finally, selected materials will be seeded with fibroblasts and injected into nude mice for in vivo tissue generation.

* Information listed above is at the time of submission. *

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