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Biomaterial, Mechanical and Molecular Strategies to Control Skin Mechanics

Blackstone, Britani Nicole

Abstract Details

2014, Doctor of Philosophy, Ohio State University, Biomedical Engineering.
Split-thickness autograft is the standard treatment for full-thickness burns. In large burns, sparse availability of uninjured skin prevents rapid closure of the wound, resulting in increased scar tissue formation or mortality. Tissue-engineered skin (ES) offers promise when autografts are not available. Unfortunately, current generations of ES are orders of magnitude weaker than normal human skin causing them to be difficult to apply surgically, subject to damage by mechanical shear in the early phases of engraftment and less elastic and weaker once grafted. To enhance and tune ES biomechanics, a coaxial (CoA) electrospun scaffold platform was developed from polycaprolactone (PCL, core) and gelatin (shell). CoA ES exhibited increased cellular adhesion and metabolism versus PCL alone or gelatin-PCL blend and promoted the development of well stratified skin with a dense dermal layer and a differentiated epidermal layer. Biomechanics of the scaffold and ES scaled linearly with core diameter suggesting that this scaffold platform could be utilized to tailor ES mechanics for their intended grafting site and reduce graft damage in vitro and in vivo. To further enhance the mechanics of the coaxial scaffold, CoA scaffolds with cores of polylactic acid (PLA) and PCL and shells of gelatin were fabricated along with pure gelatin scaffolds and grafted onto athymic mice. Coaxial scaffolds were effective at preventing wound contracture but were not stable on the animal with the human epidermis largely replaced with mouse epidermis by week 10. The strength and stiffness of the ES were significantly greater than pure gelatin in vitro however after engraftment, mechanics of the gelatin improved greatly whereas little change was observed for the coaxial groups. Large quantities of macrophages were also seen in the coaxial groups throughout the entire duration of the study. Though coaxial scaffold could provide tailored mechanics in vitro, they elicited a strong host response, eliminating them as an option for in vivo use. As a result, methods to encourage ECM deposition in vitro were evaluated. Previous efforts to mechanically stimulate ES have significantly improved ES mechanics when compared to traditionally cultured ES, however, they are only modest improvements when compared to native human skin. The addition of cyclic strain to the previously studied static strain elicited further increases in ES strength; however the end result was still far below native human skin. To better understand why mechanical stimulation only produced most improvements in ES mechanics, acellular scaffold response to strain was investigated. Non-woven electrospun scaffolds underwent very little microstructural reorganization during mechanical stimulation, while lyophilized collagen scaffolds underwent significant micro-structural changes. These differences in scaffold response suggest that large stain magnitudes may be required to excite cells within electrospun scaffolds, while modest strain magnitudes may result in significant changes in cellular behavior within lyophilized collagen sponges. Overall, these studies suggest that a better understanding of cell-scaffold interaction and the role of cell level strain on ECM deposition must be better understood in order to encourage a more natural skin morphogenesis and maturation process.
Heather Powell (Advisor)
Samir Ghadiali (Committee Member)
Douglas Kniss (Committee Member)
Abigail Shoben (Committee Member)
173 p.

Recommended Citations

Citations

  • Blackstone, B. N. (2014). Biomaterial, Mechanical and Molecular Strategies to Control Skin Mechanics [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1406123409

    APA Style (7th edition)

  • Blackstone, Britani. Biomaterial, Mechanical and Molecular Strategies to Control Skin Mechanics. 2014. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1406123409.

    MLA Style (8th edition)

  • Blackstone, Britani. "Biomaterial, Mechanical and Molecular Strategies to Control Skin Mechanics." Doctoral dissertation, Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1406123409

    Chicago Manual of Style (17th edition)