A Novel Three-Dimensional Wound Healing Model

Wound healing is a well-orchestrated process, with various cells and growth factors coming into the wound bed at a specific time to influence the healing. Understanding the wound healing process is essential to generating wound healing products that help with hard-to-heal acute wounds and chronic wo...

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Main Authors: Zhuo J. Chen, Jessica P. Yang, Benjamin M. Wu, Bill Tawil
Format: Article
Language:English
Published: MDPI AG 2014-12-01
Series:Journal of Developmental Biology
Subjects:
Online Access:http://www.mdpi.com/2221-3759/2/4/198
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author Zhuo J. Chen
Jessica P. Yang
Benjamin M. Wu
Bill Tawil
author_facet Zhuo J. Chen
Jessica P. Yang
Benjamin M. Wu
Bill Tawil
author_sort Zhuo J. Chen
collection DOAJ
description Wound healing is a well-orchestrated process, with various cells and growth factors coming into the wound bed at a specific time to influence the healing. Understanding the wound healing process is essential to generating wound healing products that help with hard-to-heal acute wounds and chronic wounds. The 2D scratch assay whereby a wound is created by scratching a confluent layer of cells on a 2D substrate is well established and used extensively but it has a major limitation—it lacks the complexity of the 3D wound healing environment. Established 3D wound healing models also have many limitations. In this paper, we present a novel 3D wound healing model that closely mimics the skin wound environment to study the cell migration of fibroblasts and keratinocytes. Three major components that exist in the wound environment are introduced in this new model: collagen, fibrin, and human foreskin fibroblasts. The novel 3D model consists of a defect, representing the actual wound, created by using a biopsy punch in a 3D collagen construct. The defect is then filled with collagen or with various solutions of fibrinogen and thrombin that polymerize into a 3D fibrin clot. Fibroblasts are then added on top of the collagen and their migration into the fibrin—or collagen—filled defect is followed for nine days. Our data clearly shows that fibroblasts migrate on both collagen and fibrin defects, though slightly faster on collagen defects than on fibrin defects. This paper shows the visibility of the model by introducing a defect filled with fibrin in a 3D collagen construct, thus mimicking a wound. Ongoing work examines keratinocyte migration on the defects of a 3D construct, which consists of collagen-containing fibroblasts. The model is also used to determine the effects of various growth factors, delivered in the wound defects, on fibroblasts’ and keratinocytes’ migration into the defects. Thus this novel 3D wound healing model provides a more complex wound healing assay than existing wound models.
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spelling doaj.art-b5266fbd957c49328c4375b73b3f2c0a2022-12-22T02:08:15ZengMDPI AGJournal of Developmental Biology2221-37592014-12-012419820910.3390/jdb2040198jdb2040198A Novel Three-Dimensional Wound Healing ModelZhuo J. Chen0Jessica P. Yang1Benjamin M. Wu2Bill Tawil3Department of Bioengineering, UCLA School of Engineering, 420 Westwood Plaza, Los Angeles, CA 90095-1600, USADepartment of Bioengineering, UCLA School of Engineering, 420 Westwood Plaza, Los Angeles, CA 90095-1600, USADepartment of Bioengineering, UCLA School of Engineering, 420 Westwood Plaza, Los Angeles, CA 90095-1600, USADepartment of Bioengineering, UCLA School of Engineering, 420 Westwood Plaza, Los Angeles, CA 90095-1600, USAWound healing is a well-orchestrated process, with various cells and growth factors coming into the wound bed at a specific time to influence the healing. Understanding the wound healing process is essential to generating wound healing products that help with hard-to-heal acute wounds and chronic wounds. The 2D scratch assay whereby a wound is created by scratching a confluent layer of cells on a 2D substrate is well established and used extensively but it has a major limitation—it lacks the complexity of the 3D wound healing environment. Established 3D wound healing models also have many limitations. In this paper, we present a novel 3D wound healing model that closely mimics the skin wound environment to study the cell migration of fibroblasts and keratinocytes. Three major components that exist in the wound environment are introduced in this new model: collagen, fibrin, and human foreskin fibroblasts. The novel 3D model consists of a defect, representing the actual wound, created by using a biopsy punch in a 3D collagen construct. The defect is then filled with collagen or with various solutions of fibrinogen and thrombin that polymerize into a 3D fibrin clot. Fibroblasts are then added on top of the collagen and their migration into the fibrin—or collagen—filled defect is followed for nine days. Our data clearly shows that fibroblasts migrate on both collagen and fibrin defects, though slightly faster on collagen defects than on fibrin defects. This paper shows the visibility of the model by introducing a defect filled with fibrin in a 3D collagen construct, thus mimicking a wound. Ongoing work examines keratinocyte migration on the defects of a 3D construct, which consists of collagen-containing fibroblasts. The model is also used to determine the effects of various growth factors, delivered in the wound defects, on fibroblasts’ and keratinocytes’ migration into the defects. Thus this novel 3D wound healing model provides a more complex wound healing assay than existing wound models.http://www.mdpi.com/2221-3759/2/4/198fibrin3D constructcell migration
spellingShingle Zhuo J. Chen
Jessica P. Yang
Benjamin M. Wu
Bill Tawil
A Novel Three-Dimensional Wound Healing Model
Journal of Developmental Biology
fibrin
3D construct
cell migration
title A Novel Three-Dimensional Wound Healing Model
title_full A Novel Three-Dimensional Wound Healing Model
title_fullStr A Novel Three-Dimensional Wound Healing Model
title_full_unstemmed A Novel Three-Dimensional Wound Healing Model
title_short A Novel Three-Dimensional Wound Healing Model
title_sort novel three dimensional wound healing model
topic fibrin
3D construct
cell migration
url http://www.mdpi.com/2221-3759/2/4/198
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