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A Paradigm of Fibroblast Activation and Dermal Wound Contraction to Guide the Development of Therapies for Chronic Wounds and Pathologic Scars.

ABSTRACT: Delayed wound healing and pathologic scarring are abnormal processes that can be thought of as occurring on a wound healing continuum, where insufficient wound contraction leads to nonhealing wounds, and overexuberant wound contraction leads to scarring. Chronic nonhealing wounds, including diabetic foot wounds, decubitus ulcers, and venous stasis ulcers, affect millions of people annually in the United States and costs billions of dollars. Similarly, pathologic scaring affects more than 40 million Americans annually and also costs billions of dollars.While there are multiple factors that contribute to chronic nonhealing wounds and pathologic scars, a derangement in wound contraction is common to both. In this article, we will present a paradigm of dermal wound contraction, derived from clinical observations and basic science evidence, which pertains to chronic nonhealing wounds and pathologic scars.We will review how select therapies currently under investigation and in development fit the paradigm.The paradigm will facilitate translational research and enable the development of future innovative therapies.

SUBMITTER: Levinson H

PROVIDER: S-EPMC3840547 | biostudies-other | 2013 May

REPOSITORIES: biostudies-other

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A Paradigm of Fibroblast Activation and Dermal Wound Contraction to Guide the Development of Therapies for Chronic Wounds and Pathologic Scars.

Levinson Howard H

Advances in wound care 20130501 4

<h4>Significance</h4>Delayed wound healing and pathologic scarring are abnormal processes that can be thought of as occurring on a wound healing continuum, where insufficient wound contraction leads to nonhealing wounds, and overexuberant wound contraction leads to scarring. Chronic nonhealing wounds, including diabetic foot wounds, decubitus ulcers, and venous stasis ulcers, affect millions of people annually in the United States and costs billions of dollars. Similarly, pathologic scaring affe ...[more]

PMID: 24527338

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Project description:Current cellular hydrogel-based skin grafts composed of human dermal fibroblasts and a hydrogel scaffold tend to minimize contraction of full-thickness skin wounds and support skin regeneration. However, there has been no comparison between the sources of the dermal fibroblast used. Products using human adult or neonatal foreskin dermal fibroblasts are often expanded in vitro and used after multiple passages without a clear understanding of the effects of this initial production step on the quality and reproducibility of the cellular behavior. Based on the known effects of 2D tissue culture expansion on cellular proliferation and gene expression, we hypothesized that differences in donor age and time in culture may influence cellular properties and contractile behavior in a fibroblast-populated collagen matrix. Using porcine skin as a model based on its similarity to human skin in structure and wound healing properties, we isolated porcine dermal fibroblasts of three different donor ages for use in a 2D proliferation assay and in a 3D cell-populated collagen matrix contractility assay. In 2D cell culture, doubling time remained relatively consistent between all age groups from passage 1 to 6. In the contractility assays, fetal and neonatal groups contracted faster and generated more contractile force than the adult group at passage 1 in vitro. However, after five passages in culture, there was no difference in contractility between ages. These results show how cellular responses in a hydrogel scaffold differ based on donor age and time in culture in vitro, and suggest that consistency in the cellular component of bioengineered skin products could be beneficial in the biomanufacturing of consistent, reliable skin grafts and graft in vivo models. Future research and therapies using bioengineered skin grafts should consider how results may vary based on donor age and time in culture before seeding. Impact statement Little is known about the impact of donor cell age and time in culture on the contraction of cellular, hydrogel-based skin grafts. These results show how cellular phenotypes of porcine fibroblasts differ based on donor age and time in culture. This information is beneficial when addressing important inconsistencies in biomanufacturing of bioengineered skin grafts and in vitro models. These findings are relevant to research and therapies using bioengineered skin graft models and the results can be used to increase reproducibility and consistency during the production of bioengineered skin constructs. The information from this study can be extrapolated to future in vivo studies using human dermal fibroblasts in an in vivo model to help determine the best donor age and time in culture for optimal wound healing outcomes or more reproducible in vitro testing constructs.

Dataset Information

A Paradigm of Fibroblast Activation and Dermal Wound Contraction to Guide the Development of Therapies for Chronic Wounds and Pathologic Scars.

Publications

A Paradigm of Fibroblast Activation and Dermal Wound Contraction to Guide the Development of Therapies for Chronic Wounds and Pathologic Scars.

Similar Datasets

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