Cell infiltrative hydrogel fibrous scaffolds for accelerated wound healing.
Development of natural protein-based fibrous scaffolds with tunable physical properties and biocompatibility is highly desirable to construct three-dimensional (3D), fully cellularized scaffolds for wound healing. Herein, we demonstrated a simple and effective technique to construct electrospun 3D fibrous scaffolds for accelerated wound healing using a photocrosslinkable hydrogel based on gelatin methacryloyl (GelMA). We found that the physical properties of the photocrosslinkable hydrogel including water retention, stiffness, strength, elasticity and degradation can be tailored by changing the light exposure time. We further observed that the optimized hydrogel fibrous scaffolds which were soft and elastic could support cell adhesion, proliferation and migration into the whole scaffolds, facilitating regeneration and formation of cutaneous tissues within two weeks. Such tunable characteristics of the fibrous GelMA scaffolds distinguished them from other reported substrates developed for reconstruction of wound defects including glutaraldehyde-crosslinked gelatin or poly (lactic-co-glycolic acid) (PLGA), whose physical and chemical properties were difficult to modify to allow cell infiltration into the 3D scaffolds for tissue regeneration. We anticipate that the ability to become fully cellularized will make the engineered GelMA fibrous scaffolds suitable for widespread applications as skin substitutes or wound dressings.



In present study, we generate three-dimensional photocrosslinkable gelatin (GelMA)-based fibrous scaffolds with tunable physical and biological properties by using a combined photocrosslinking/electrospinning approach. The developed GelMA fibrous scaffolds can not only support cell viability and cell adhesion, but also facilitate cell migration and proliferation, accelerating regeneration and formation of cutaneous tissues. In addition, the physical properties of the engineered fibrous GelMA hydrogel including water retention capability, mechanical properties and biodegradability can be tuned to accommodate different patients' needs, making it a promising candidate for skin tissue engineering.
Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA; School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China; Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Shaanxi 710049, China.
Xin
X
Zhao
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University of Medicine, Shanghai 200011, China.
Xiaoming
X
Sun
Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA.
Lara
L
Yildirimer
Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA.
Qi
Q
Lang
Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA.
Zhi Yuan William
ZYW
Lin
Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA.
Reila
R
Zheng
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University of Medicine, Shanghai 200011, China.
Yuguang
Y
Zhang
Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, Jiangsu 215006, China. Electronic address: wgcui80@hotmail.com.
Wenguo
W
Cui
Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA; Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA. Electronic address: n.annabi@neu.edu.
Nasim
N
Annabi
Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Department of Physics, King Abdulaziz University, Jeddah 21569, Saudi Arabia. Electronic address: alik@bwh.harvard.edu.
Ali
A
Khademhosseini
D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D005260:Female; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry; D008689:Methacrylates / Q000737:chemistry; D008813:Mice, Inbred ICR; D057139:Nanofibers / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D062326:Re-Epithelialization / Q000187:drug effects; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects*
D008689:Methacrylates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005780:Gelatin; D003094:Collagen
Gelatin methacryloyl; Photocrosslinkable hydrogel; Soft elasticity; Water retention; Wound healing