Relative distribution and crosslinking of collagen distinguish fetal from adult sheep wound repair

Lovvorn, Harold N.; Cheung, David T.; Nimni, Marcel E.; Perelman, Natasha; Estes, James M.; Adzick, N. Scott

doi:10.1016/s0022-3468(99)90261-0

Cited by 104 publications

(72 citation statements)

References 14 publications

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“…65,66 In scarless fetal skin, collagen III comprises *30-60% of the total collagen compared to 10-20% in adult skin. 66,67 Wounding in this unique setting triggers a complex cascade of tightly controlled events resulting in a scarless phenotype, typically consisting of fine reticular collagen and abundant HA. 2 Scarless repair, however, is dependent on gestational age.…”

Section: Ecm Remodelling In Fetal Cutaneous Scarless Healingmentioning

confidence: 99%

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

Xue

Jackson

2015

Advances in Wound Care

1,033

866

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Significance: When a cutaneous injury occurs, the wound heals via a dynamic series of physiological events, including coagulation, granulation tissue formation, re-epithelialization, and extracellular matrix (ECM) remodeling. The final stage can take many months, yet the new ECM forms a scar that never achieves the flexibility or strength of the original tissue. In certain circumstances, the normal scar is replaced by pathological fibrotic tissue, which results in hypertrophic or keloid scars. These scars cause significant morbidity through physical dysfunction and psychological stress. Recent Advances and Critical Issues: The cutaneous ECM comprises a complex assortment of proteins that was traditionally thought to simply provide structural integrity and scaffolding characteristics. However, recent findings show that the ECM has multiple functions, including, storage and delivery of growth factors and cytokines, tissue repair and various physiological functions. Abnormal ECM reconstruction during wound healing contributes to the formation of hypertrophic and keloid scars. Whereas adult wounds heal with scarring, the developing foetus has the ability to heal wounds in a scarless fashion by regenerating skin and restoring the normal ECM architecture, strength, and function. Recent studies show that the lack of inflammation in fetal wounds contributes to this perfect healing. Future Directions: Better understanding of the exact roles of ECM components in scarring will allow us to produce therapeutic agents to prevent hypertrophic and keloid scars. This review will focus on the components of the ECM and their role in both physiological and pathological (hypertrophic and keloid) cutaneous scar formation. SCOPE AND SIGNIFICANCEThis article reviews the extracellular matrix (ECM) and its remodeling during normal cutaneous wound healing and scar formation, and the differential response of the components of the ECM and their role in pathological (hypertrophic and keloid) cutaneous scar formation. This review focuses on the major players involved in the irregular ECM production as being; fibroblasts and their immature counterparts, myofibroblasts; collagens; transforming growth factor (TGF)-b, which controls the production of collagens; proteoglycans and matrix metalloproteinases (MMPs). We also highlight the complexity of interactions occurring in the ECM of skin during (ab) normal scar formation. TRANSLATIONAL RELEVANCEAbnormal ECM, particularly abnormal collagen remodeling and reorganization, accounts for one of the most important contributing factors to abnormal scarring. Identification of the exact ECM molecules involved in causing abnormal scarring is likely to provide a future treatment target. This may be achieved by promoting the correct balance in collagen ratios or by directly targeting the production of collagen. Overall, a better understanding of the exact roles of ECM components in scarring will help us to produce therapeutic agents to prevent and treat hypertrophic and keloid scars. CLINICAL RELEVANCEThere ...

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Section: Ecm Remodelling In Fetal Cutaneous Scarless Healingmentioning

confidence: 99%

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

Xue

Jackson

2015

Advances in Wound Care

1,033

866

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“…A similar effect of age on collagen elaboration has been observed in other connective tissues such as tendon and skin [9,54]. In an in vivo sheep skin injury model, Lovvorn et al observed more rapid deposition of Type I collagen and greater collagen cross-linking in early gestational fetal skin wounds in comparison to adult skin, which correlated with scarless healing [36]. The proficiency of fetal ACL fibroblasts to secrete considerably more Type I collagen than adult ACL fibroblasts supports the notion that the healing potential of the ACL may vary with age.…”

Section: Discussionmentioning

confidence: 58%

“…Scarlessly healing fetal tissues also have elevated levels of Type III collagen in comparison to adult tissues, suggesting specific collagen expression profiles associated with regenerative healing [11,36,51]. Although the secretion of Type I collagen is critical to restore tissue structure and function in the healing ACL, the presence of other collagens, such as Type III collagen, also may play a role in wound healing progression.…”

Section: Introductionmentioning

confidence: 99%

Fetal ACL Fibroblasts Exhibit Enhanced Cellular Properties Compared with Adults

Stalling

Nicoll

2008

Clinical Orthopaedics &Amp; Related Research

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Fetal tendons and skin heal regeneratively without scar formation. Cells isolated from these fetal tissues exhibit enhanced cellular migration and collagen production in comparison to cells from adult tissue. We determined whether fetal and adult fibroblasts isolated from the anterior cruciate ligament (ACL), a tissue that does not heal regeneratively, exhibit differences in cell migration rates and collagen elaboration. An in vitro migration assay showed fetal ACL fibroblasts migrated twice as fast as adult ACL fibroblasts at a rate of 38.90 ± 7.69 lm per hour compared with 18.88 ± 4.18 lm per hour, respectively. Quantification of Type I collagen elaboration by enzymelinked immunosorbent assay showed fetal ACL fibroblasts produced four times the amount of Type I collagen compared with adult ACL fibroblasts after 7 days in culture. We observed no differences in Type III collagen with time for adult or fetal ACL fibroblasts. Our findings indicate fetal ACL fibroblasts are intrinsically different from adult ACL fibroblasts, suggesting the healing potential of the ACL may be age-dependent.

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“…[14][15][16] This process strengthens the repaired tissue over the course of 6-12 months. 17 The remodeling phase lasts for a year or more. 8 The strength of previously wounded skin is at most 75-80% that of unwounded skin.…”

Section: Discussion Of Findings and Relevant Literature Overview Of Umentioning

confidence: 99%

Mechanical Forces in Cutaneous Wound Healing: Emerging Therapies to Minimize Scar Formation

Barnes

Marshall

Leavitt

et al. 2018

Advances in Wound Care

161

131

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Significance: Excessive scarring is major clinical and financial burden in the United States. Improved therapies are necessary to reduce scarring, especially in patients affected by hypertrophic and keloid scars. Recent Advances: Advances in our understanding of mechanical forces in the wound environment enable us to target mechanical forces to minimize scar formation. Fetal wounds experience much lower resting stress when compared with adult wounds, and they heal without scars. Therapies that modulate mechanical forces in the wound environment are able to reduce scar size. Critical Issues: Increased mechanical stresses in the wound environment induce hypertrophic scarring via activation of mechanotransduction pathways. Mechanical stimulation modulates integrin, Wingless-type, protein kinase B, and focal adhesion kinase, resulting in cell proliferation and, ultimately, fibrosis. Therefore, the development of therapies that reduce mechanical forces in the wound environment would decrease the risk of developing excessive scars. Future Directions: The development of novel mechanotherapies is necessary to minimize scar formation and advance adult wound healing toward the scarless ideal. Mechanotransduction pathways are potential targets to reduce excessive scar formation, and thus, continued studies on therapies that utilize mechanical offloading and mechanomodulation are needed.

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Relative distribution and crosslinking of collagen distinguish fetal from adult sheep wound repair

Cited by 104 publications

References 14 publications

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

Fetal ACL Fibroblasts Exhibit Enhanced Cellular Properties Compared with Adults

Mechanical Forces in Cutaneous Wound Healing: Emerging Therapies to Minimize Scar Formation

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