A novel, sterilized microvascular tissue product improves healing in a murine pressure ulcer model

Jeffrey M. Gimble, Trivia Frazier, Xiying Wu, Andrea Alarcon Uquillas, Claire Llamas, Theodore Brown, Doan Nguyen, H. Alan Tucker, Douglas M. Arm, Dale R. Peterson, Bruce A. Bunnell

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Processed microvascular tissue (PMVT), a human structural allograft, is derived from lyophilized human tissue containing microcirculatory cellular components. Since PMVT serves as a source of extracellular matrix (ECM), growth factors, cytokines, and chemokines modulating angiogenesis, inflammation, apop-tosis, and endogenous cell recruitment, we hypothesized its application would accelerate wound regeneration in a validated pressure ulcer (PU) model developed in C57BL/6 mice using two 24-hour cycles of skin ischemia/reperfusion created by placement and removal of external magnets. Methods: Two identical PU injuries (n = 50 female mice) were treated with (a) topical particulate PMVT, (b) injected rehydrated PMVT, or (c) saline control injection, and assessed daily for closure rates, scab formation/removal, and temperature. A baseline control cohort (n = 5) was euthanized at day 0 and treatment group cohorts (n = 5) were killed at 3, 7, or 14 days postinjury. The PU injuries were collagenase-digested for flow cytometric analysis of inflammatory, reparative, and stem cell frequencies and analyzed by hematoxylin and eosin (H&E) histology and immunofluorescence. Results: PMVT-accelerated wound closure, most notably, topical PMVT significantly increased mean closure from d5 (13% versus 9%) through d13 (92% versus 38%) compared with phosphate-buffered saline (PBS) controls (P < 0.05). PMVT also hastened scab formation/removal, significantly accelerated disappearance of inflammatory myeloid (CD11b+) cells while upregulating α-smooth muscle actin, vascular endothelial growth factor A, and placental growth factor and raised skin temperature surrounding the PU site, consistent with increased blood flow. Conclusions: These results indicate that PMVT has potential as an advanced treatment for restoring normal tissue function in ischemic wounds and merits clinical study.

Original languageEnglish
Article numbere2010
JournalPlastic and Reconstructive Surgery - Global Open
Volume6
Issue number11
DOIs
StatePublished - 2018

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    Gimble, J. M., Frazier, T., Wu, X., Uquillas, A. A., Llamas, C., Brown, T., Nguyen, D., Alan Tucker, H., Arm, D. M., Peterson, D. R., & Bunnell, B. A. (2018). A novel, sterilized microvascular tissue product improves healing in a murine pressure ulcer model. Plastic and Reconstructive Surgery - Global Open, 6(11), [e2010]. https://doi.org/10.1097/GOX.0000000000002010