Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

Abstract

Progress in biomaterial science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and controlling the cellular microenvironment of the wound tissue are important to improve the wound healing process. In this study, we review different biochemical (e.g., growth factors, peptides, DNA, and RNA) and biophysical (e.g., topographical guidance, pressure, electrical stimulation, and pulsed electromagnetic field) cues providing a functional and instructive acellular matrix to heal diabetic chronic wounds. The biochemical and biophysical signals generally regulate cell-matrix interactions and cell behavior and function inducing the tissue regeneration for chronic wounds. Some technologies and devices have already been developed and used in the clinic employing biochemical and biophysical cues for wound healing applications. These technologies can be integrated with smart biomaterials to deliver therapeutic agents to the wound tissue in a precise and controllable manner. This review provides useful guidance in understanding molecular mechanisms and signals in the healing of diabetic chronic wounds and in designing instructive biomaterials to treat them.

Keywords: biomaterial; diabetic; dressing; matrix; wound healing.

FIG. 1.

Various biochemical and biophysical cues provided by matrix to regulate the native cell response. Growth factors and derivatives can interact with native cells through their specific receptors. The composition of ECM proteins is usually recognized by integrins. Small bioactive molecules, including oxygen and NO, can diffuse into the cells and mainly affect mitochondrial activities. Genetic regulators, including cDNA, miRNA, and siRNA, can be delivered by nonviral vehicles and facilitate gene transcription and translation. Electric or magnetic cues can also influence cell responses such as migration. cDNA, complementary DNA; ECM, extracellular matrix; miRNA, microRNA; NO, nitric oxide; siRNA, small interfering RNA. Color images available online at www.liebertpub.com/teb

FIG. 2.

Engineered biomaterials using topographical guidance. (a) Schematic of wound treatment using a microgrooved PDMS patch. (b) Porous polymer matrix fabricated by sphere templating. (c) Electrospun fibers aligned in radial orientation. (d) Microisland arrays of electrospun nanofibers. Reproduced with the permission from Refs.^,,, Copyrights 2012 Royal Society of Chemistry, 2012 John Wiley and Sons, 2010 American Chemical Society, and 2010 John Wiley and Sons, respectively. PDMS, polydimethylsiloxane. Color images available online at www.liebertpub.com/teb

FIG. 3.

A commercially available vacuum-assisted wound closure device (KCI's proprietary V.A.C.^® Therapy System). The macrostrain assists in the excessive fluid removal (arrows indicate exudant flow), tissue edema reduction, and blood flow optimization (arrows indicate vessel dilatation). Courtesy of KCI, an Acelity Company. © 2015 KCI. Color images available online at www.liebertpub.com/teb

FIG. 4.

Schematic diagram of design, application (a), and electric fields (b) generated by Procellera^® bioelectric dressing. Courtesy of Banerjee et al. Color images available online at www.liebertpub.com/teb

FIG. 5.

Diagram of the design and magnetic field generated by RecoveryRx^® medical device (a) and its application on human body (b). Color images available online at www.liebertpub.com/teb