Bioactive scaffolds for therapeutic angiogenesis on skin injuries and vascular disease model

angiogenesis;hydrogel;burn;skin;diabetic;stemcell;Chemical & Biomolecular Engineering

Shen, Yu-IMao, Hai-Quan ;

Johns Hopkins University

关键词: angiogenesis;    hydrogel;    burn;    skin;    diabetic;    stemcell;    Chemical & Biomolecular Engineering;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/40675/SHEN-DISSERTATION-2015.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Angiogenesis, defined as the formation of blood vessels from pre-existing vessels, is an important natural process. While angiogenesis does not occur in healthy mammals. it plays a major role in tumor development and wound healing. The tightly controlled process of angiogenesis is dependent on a variety of biochemical and biomechanical cues. Using synthetic bioactive hydrogel systems allows us to investigate this well controlled process. For instance, many have adapted three dimensional (3D) tissue culture models that recapitulate aspects of the tumorogenic in vivo microenvironment to study cancer progression in vitro and its linkage with angiogenesis. At the same time, a 3D tissue culture bioactive scaffolds can also provide a therapeutic strategy to treat various injuries and diseases.First we utilized hyaluronic acid hydrogel systems and using mathematical modeling, found that varying viscoelasticity in atmospheric and hypoxic environments affects cancer cell cycles and the expression of autophagy and apoptosis genes. Hypoxic stress enabled greater recovery from apoptosis through autophagy mechanism and induced greater angiogenic leading to extensive endothelial cell (EC) sprouting. Next we used the same hyaluronic acid hydrogel engineer human microvasculature for the treatment of diabetic foot ulcers (DFUs), one of the leading healthcare problems in the US. To this end, we developed an immunodeficient diabetes rodent DFU model. Treatment of DFU with engineered human vascularized hydrogel scaffolds from stem cell derived vascular cells, has shown faster wound healing compared to acellular hydrogel, thus suggestion a potential therapeutic strategy to treat DFU. Finally, we investigated the utilization of dextran hydrogel system to induce vascularization and healing of third degree burn injuries in a large animal model. We have observed accelerated third degree burn wound healing in porcine by rapid wound closure, improved re-epitheliazation, enhanced extracellular matrix remodeling and greater nerve re-innervation in the hydrogel treated wounds.Collectively, the results from this thesis showcase the successfully utilization of bioactive hydrogel scaffolds to study various biochemical and biophysical cues that influence angiogenesis. Combing with stem cell technologies, the hydrogel systems can improve wound healing at both diseased and severe skin injuries.