Keratinocyte Migration in a Three-Dimensional In Vitro Wound Healing Model Co-Cultured with Fibroblasts

Kritika Iyer; Zhuo Chen; Teja Ganapa; Benjamin M. Wu; Bill Tawil; Chase S. Linsley

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자료유형: 학술저널

저자정보: Kritika Iyer (University of California Los Angeles) Zhuo Chen (University of California Los Angeles) Teja Ganapa (University of California Los Angeles) Benjamin M. Wu (University of California Los Angeles) Bill Tawil (University of California Los Angeles) Chase S. Linsley (University of California Los Angeles)

저널정보: 한국조직공학과 재생의학회 조직공학과 재생의학 조직공학과 재생의학 제15권 제6호

발행연도: 2018.1

수록면: 721 - 733 (13page)

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BACKGROUND: Because three-dimensional (3D) models more closely mimic native tissues, one of the goals of 3D in vitro tissue models is to aid in the development and toxicity screening of new drug therapies. In this study, a 3D skin wound healing model comprising of a collagen type I construct with fibrin-filled defects was developed. METHODS: Optical imaging was used to measure keratinocyte migration in the presence of fibroblasts over 7 days onto the fibrin-filled defects. Additionally, cell viability and growth of fibroblasts and keratinocytes was measured using the alamarBlue assay and changes in the mechanical stiffness of the 3D construct was monitored using compressive indentation testing. RESULTS: Keratinocyte migration rate was significantly increased in the presence of fibroblasts with the cells reaching the center of the defect as early as day 3 in the co-culture constructs compared to day 7 for the control keratinocyte monoculture constructs. Additionally, constructs with the greatest rate of keratinocyte migration had reduced cell growth. When fibroblasts were cultured alone in the wound healing construct, there was a 1.3 to 3.4-fold increase in cell growth and a 1.2 to 1.4-fold increase in cell growth for keratinocyte monocultures. However, co-culture constructs exhibited no significant growth over 7 days. Finally, mechanical testing showed that fibroblasts and keratinocytes had varying effects on matrix stiffness with fibroblasts degrading the constructs while keratinocytes increased the construct’s stiffness. CONCLUSION: This 3D in vitro wound healing model is a step towards developing a mimetic construct that recapitulates the complex microenvironment of healing wounds and could aid in the early studies of novel therapeutics that promote migration and proliferation of epithelial cells.

참고문헌 (66)

참고문헌 신청

Eming SA / 2014 / Wound repair and regeneration: mechanisms, signaling, and translation / Sci Transl Med 6:265~266

Sen CK / 2009 / Human skin wounds : a major and snowballing threat to public health and the economy / Wound Repair Regen 17:763~771

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Mostow EN / 2005 / Effectiveness of an extracellular matrix graft(OASIS Wound Matrix)in the treatment of chronic leg ulcers : a randomized clinical trial / J Vasc Surg 41:837~843

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