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Title TGFß functionalized starPEG-heparin hydrogels modulate human dermal fibroblast growth and differentiation
Date 01.10.2015
Number 47942
Abstract Hydrogels are promising biomaterials that can adapt easily to complex tissue entities. Furthermore, chemical modifications enable these hydrogels to become an instructive biomaterial to a variety of cell types. Human dermal fibroblasts play a pivotal role during wound healing, especially for the synthesis of novel dermal tissue replacing the primary fibrin clot. Thus, the control of growth and differentiation of dermal fibroblasts is important to modulate wound healing. In here, we utilized a versatile starPEG-heparin hydrogel platform that can be independently adjusted with respect to mechanical and biochemical properties for cultivating human dermal fibroblasts. Cell-based remodeling of the artificial matrix was ensured by using matrix metalloprotease (MMP) cleavable crosslinker peptides. Attachment and proliferation of fibroblasts on starPEG-heparin hydrogels of differing stiffness, density of pro-adhesive RGD peptides and MMP cleavable peptide linkers were tested. Binding and release of human TGFß1 as well as biological effect of the pre-adsorbed growth factor on fibroblast gene expression and myofibroblast differentiation were investigated. Hydrogels containing RGD peptides supported fibroblast attachment, spreading, proliferation matrix deposition and remodeling compared to hydrogels without any modifications. Reversibly conjugated TGFß1 was demonstrated to be constantly released from starPEG-heparin hydrogels for several days and capable of inducing myofibroblast differentiation of fibroblasts as determined by induction of collagen type I, ED-A-Fibronectin expression and incorporation of alpha smooth muscle actin and palladin into F-actin stress fibers. Taken together, customized starPEG-heparin hydrogels could be of value to promote dermal wound healing by stimulating growth and differentiation of human dermal fibroblasts.
URL http://dx.doi.org/10.1016/j.actbio.2015.07.036
Publisher Acta Biomaterialia
Identifier 0
Citation Acta Biomaterialia 25 (2015) 65-75
DOI http://dx.doi.org/10.1016/j.actbio.2015.07.036
Authors Watarai, A. ; Schirmer, L. ; Thönes, S. ; Freudenberg, U. ; Werner, C. ; Simon, J. C. ; Anderegg, U.
Tags starpeg heparin hydrogels wound healing myofibroblast alpha-smooth muscle actin (asma) extracellular matrix (ecm) metalloprotease (mmp)

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