Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering.
The aim of this study was to design a dermal substitute containing adipose derived stem cells (ADSC) that can be used to improve the regeneration of skin on difficult wound beds by stimulating rapid neovascularization. This was achieved by first synthesizing methacrylated gelatin (GelMA) and methacrylated hyaluronic acid (HAMA) precursors which could be stored at -80oC after lyophilisation. Polymer precursors were then dissolved in media (in 15:1 ratio), ADSCs added together with the photoinitiator and crosslinked with 40 s of UV. Hydrogels degraded by 50% over 3 weeks in an in vitro environment. ADSC loaded hydrogels could be easily handled with forceps (compressive modulus was 6 kPa). Transparency of the gel would allow a full field-of-view of a wound site. The hydrogels provided a suitable microenvironment for ADSC proliferation as shown by the filopodia observed in confocal micrographs. In vivo studies demonstrated that stem cell loaded hydrogels increased vascularization by up to 3 fold compared to their cell free counterparts. In conclusion, GelMA/HAMA hydrogels loaded with ADSC showed the desired proliferative and angiogenic properties essential to promote angiogenesis for wound healing and improving survival of tissue engineered skin.
Middle East Technical University (METU), Department of Biotechnology, 06800 Ankara, Turkey; BIOMATEN, METU Center of Excellence in Biomaterials and Tissue Engineering, 06800 Ankara, Turkey; Ahi Evran University, Department of Chemistry, Faculty of Arts and Sciences, 40100 Kirsehir, Turkey.
Gozde
G
Eke
Department of Materials Science & Engineering, The Kroto Research Institute, University of Sheffield, Broad Lane, S3 7HQ Sheffield, United Kingdom; Royal Hallamshire Hospital, Urology Clinic, Sheffield, United Kingdom.
Naside
N
Mangir
Middle East Technical University (METU), Department of Biotechnology, 06800 Ankara, Turkey; METU, Department of Chemistry, 06800 Ankara, Turkey; BIOMATEN, METU Center of Excellence in Biomaterials and Tissue Engineering, 06800 Ankara, Turkey.
Nesrin
N
Hasirci
Department of Materials Science & Engineering, The Kroto Research Institute, University of Sheffield, Broad Lane, S3 7HQ Sheffield, United Kingdom.
Sheila
S
MacNeil
Middle East Technical University (METU), Department of Biotechnology, 06800 Ankara, Turkey; METU, Department of Biological Sciences, 06800 Ankara, Turkey; BIOMATEN, METU Center of Excellence in Biomaterials and Tissue Engineering, 06800 Ankara, Turkey. Electronic address: vhasirci@metu.edu.tr.
Vasif
V
Hasirci
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D049109:Cell Proliferation; D002470:Cell Survival; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry; D018919:Neovascularization, Physiologic; D066244:Proton Magnetic Resonance Spectroscopy; D012867:Skin / Q000098:blood supply* / Q000473:pathology; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D014466:Ultraviolet Rays; D014945:Wound Healing
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D008689:Methacrylates; C008384:methacrylic acid; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid; D004247:DNA
Adipose derived stem cells; Angiogenesis; Bicomponent hydrogel; Dermal substitute; Photocrosslinking