Designer self-assembling hydrogel scaffolds can impact skin cell proliferation and migration

There is a need to develop economical, efficient and widely available therapeutic approaches to enhance the rate of skin wound healing. The optimal outcome of wound healing is restoration to the pre-wound quality of health. In this study we investigate the cellular response to biological stimuli using functionalized nanofibers from the self-assembling peptide, RADA16. We demonstrate that adding different functional motifs to the RADA16 base peptide can influence the rate of proliferation and migration of keratinocytes and dermal fibroblasts. Relative to unmodified RADA16; the Collagen I motif significantly promotes cell migration, and reduces proliferation.

[1]  A. Barbul,et al.  General principles of wound healing. , 1997, The Surgical clinics of North America.

[2]  Fabrizio Gelain,et al.  Biological Designer Self-Assembling Peptide Nanofiber Scaffolds Significantly Enhance Osteoblast Proliferation, Differentiation and 3-D Migration , 2007, PloS one.

[3]  J. Laws State-of-the-art burn treatment. , 1996, Occupational health & safety.

[4]  S. Shapiro,et al.  Evaluation of endothelial cell migration with a novel in vitro assay system. , 2000, Methods in cell science : an official journal of the Society for In Vitro Biology.

[5]  Giles O. C. Cory Scratch-wound assay. , 2011, Methods in molecular biology.

[6]  A. Telser Molecular Biology of the Cell, 4th Edition , 2002 .

[7]  Remo Papini,et al.  Management of burn injuries of various depths , 2004, BMJ : British Medical Journal.

[8]  S. Neil What role does the extracellular matrix serve in skin grafting and wound healing , 1994 .

[9]  R. Clark,et al.  Fibronectin, as well as other extracellular matrix proteins, mediate human keratinocyte adherence. , 1985, The Journal of investigative dermatology.

[10]  M. Abercrombie,et al.  Observations on the social behaviour of cells in tissue culture. I. Speed of movement of chick heart fibroblasts in relation to their mutual contacts. , 1953, Experimental cell research.

[11]  J. Hubbell,et al.  Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: systematic modulation of a synthetic cell-responsive PEG-hydrogel. , 2008, Biomaterials.

[12]  Shuguang Zhang,et al.  Designer functionalized self-assembling peptide nanofiber scaffolds for growth, migration, and tubulogenesis of human umbilical vein endothelial cells , 2008 .

[13]  D. Woodley,et al.  Laminin inhibits human keratinocyte migration , 1988, Journal of cellular physiology.

[14]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[15]  Takatoshi Kinoshita,et al.  Dynamic reassembly of peptide RADA16 nanofiber scaffold. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Lawrence J Bonassar,et al.  Characterization of polylactic acid-polyglycolic acid composites for cartilage tissue engineering. , 2003, Tissue engineering.

[17]  S. Rizzi,et al.  Elucidating the role of matrix stiffness in 3D cell migration and remodeling. , 2011, Biophysical journal.

[18]  D. Greenhalgh,et al.  The role of apoptosis in wound healing. , 1998, The international journal of biochemistry & cell biology.

[19]  D. Woodley,et al.  Type IV collagen and fibronectin enhance human keratinocyte thymidine incorporation and spreading in the absence of soluble growth factors. , 1990, The Journal of investigative dermatology.

[20]  Shuguang Zhang,et al.  Designer self-assembling peptide nanofiber biological materials. , 2010, Chemical Society reviews.

[21]  N. Kotov,et al.  Three-dimensional cell culture matrices: state of the art. , 2008, Tissue engineering. Part B, Reviews.

[22]  Gary E. Wnek,et al.  TAILORING TISSUE ENGINEERING SCAFFOLDS USING ELECTROSTATIC PROCESSING TECHNIQUES: A STUDY OF POLY(GLYCOLIC ACID) ELECTROSPINNING , 2001 .

[23]  Sang Hoon Lee,et al.  Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells. , 2007, Biomaterials.

[24]  C. S. Izzard,et al.  Formation of cell-to-substrate contacts during fibroblast motility: an interference-reflexion study. , 1980, Journal of cell science.

[25]  Kyriacos A. Athanasiou,et al.  The effects of porosity on in vitro degradation of polylactic acid- polyglycolic acid implants used in repair of articular cartilage , 1998 .

[26]  C. Winder,et al.  The sensitivity and specificity of the MTS tetrazolium assay for detecting the in vitro cytotoxicity of 20 chemicals using human cell lines. , 1997, Toxicology.

[27]  John M. Walker,et al.  Cell Migration , 2005, Methods in Molecular Biology™.

[28]  Xiaojun Zhao,et al.  The effect of a self-assembling peptide nanofiber scaffold (peptide) when used as a wound dressing for the treatment of deep second degree burns in rats. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[29]  D. Druecke,et al.  Modulation of scar tissue formation using different dermal regeneration templates in the treatment of experimental full‐thickness wounds , 2004, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[30]  Fabrizio Gelain,et al.  Designer self-assembling peptide scaffolds for 3-d tissue cell cultures and regenerative medicine. , 2007, Macromolecular bioscience.

[31]  R. Tompkins,et al.  Artificial skin. , 2000, Annual review of medicine.

[32]  E Ruoslahti,et al.  RGD and other recognition sequences for integrins. , 1996, Annual review of cell and developmental biology.

[33]  C. M. Agrawal,et al.  Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/polyglycolic acid copolymers. , 1996, Biomaterials.

[34]  B. Atiyeh,et al.  Cultured epithelial autograft (CEA) in burn treatment: three decades later. , 2007, Burns : journal of the International Society for Burn Injuries.

[35]  S. Boyce,et al.  Burn wound closure with cultured autologous keratinocytes and fibroblasts attached to a collagen-glycosaminoglycan substrate. , 1989, JAMA.

[36]  Paul Martin,et al.  Wound Healing--Aiming for Perfect Skin Regeneration , 1997, Science.

[37]  J. McCubrey,et al.  Use of an aqueous soluble tetrazolium/formazan assay to measure viability and proliferation of lymphokine-dependent cell lines. , 1993, Journal of immunological methods.

[38]  F. Nakamura Biochemical, electron microscopic and immunohistological observations of cationic detergent-extracted cells: detection and improved preservation of microextensions and ultramicroextensions , 2001, BMC Cell Biology.

[39]  Andreas Greiner,et al.  Nanoprocessing of polymers: applications in medicine, sensors, catalysis, photonics , 2005 .