Changing the Wound: Covalent Immobilization of the Epidermal Growth Factor.

Autor:	Raghunathan V; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States.; Department of Basic Sciences, College of Optometry, University of Houston, 4901 Calhoun Rd, Houston, Texas 77204, United States.; Biomedical Engineering, Cullen College of Engineering, University of Houston, Houston, Texas 77204, United States., Park SA; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States.; Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, 625 Harrison Street, West Lafayette, Indiana 47907, United States., Shah NM; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States.; Medtronic Diabetes, 18000 Devonshire Street, Northridge, California 91325-1219, United States., Reilly CM; Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States., Teixeira L; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Dubielzig R; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Chang YR; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States., Motta MJ; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States., Schurr MJ; Divison of General Surgery, Mountain Area Health Education Center, 509 Biltmore Avenue, Asheville, North Carolina 28803, United States., McAnulty JF; Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, Wisconsin 53706, United States., Isseroff RR; Department of Dermatology, UC Davis School of Medicine, University of California Davis, Sacramento, California 95817, United States., Abbott NL; Smith School of Chemical and Biomolecular Engineering, Cornell University, 1 Hoy Plaza, Ithaca, New York 14853 United States., Murphy CJ; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, United States.; Department of Ophthalmology & Vision Science, School of Medicine, University of California Davis, One Shields Avenue, Davis, California 95817, United States.
Jazyk:	angličtina
Zdroj:	ACS biomaterials science & engineering [ACS Biomater Sci Eng] 2021 Jun 14; Vol. 7 (6), pp. 2649-2660. Date of Electronic Publication: 2021 May 21.
DOI:	10.1021/acsbiomaterials.1c00192
Abstrakt:	Re-epithelialization of wounds is a critical element of wound closure. Growth factors have been used in combination with conventional wound management to promote closure, but the method of delivery has been limited to the topical application of ointment formulations. Cytoactive factors delivered in this way have short resident times in wounds and have met with limited success. Here, we demonstrate that methods used to covalently immobilize proteins on synthetic materials can be extended to immobilize cytoactive factors such as the epidermal growth factor (EGF) onto the wound beds of genetically diabetic mice that exhibit impaired healing. Full-thickness splinted excisional wounds were created in diabetic (db/db) mice with a well-defined silicone splint to limit wound contracture. Wound surfaces were treated with a reducing agent to expose sulfhydryl groups and subsequently treated with EGF modified with a heterobifunctional crosslinker. This allowed for the covalent immobilization of the EGF to the wound surface. The conjugation chemistry was validated in vitro and in vivo. In a separate group of mice, wounds were topically treated twice daily with soluble EGF. The mice were evaluated over 11 days for wound closure. This covalent immobilization strategy resulted in EGF being retained on the wound surface for 2 days and significantly increased epithelial wound closure by 20% compared to wounds treated with topical EGF or topical vehicle. Covalent immobilization was not only therapeutically effective but also delivered a markedly reduced load of growth factor to the wound surface compared to topical application (when only 180 ng of EGF was immobilized onto the wound surface in comparison with 7200 ng of topically applied EGF over a period of 11 days). No adverse effects were observed in treated wounds. Results obtained provide proof of concept for the effectiveness of covalent immobilization in the treatment of dysregulated wounds. The covalent immobilization of cytoactive factors represents a potentially transformative approach to the management of difficult chronic wounds.
Databáze:	MEDLINE
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