Over-healing of a wound can prevent complete tissue repair
Over-healing and excessive fibrosis (such as hypertrophic scarring and pathological matrix deposition) disrupt normal tissue architecture and can prevent functional tissue repair.
Multiple studies demonstrate that excessive extracellular matrix deposition, pathological scarring, and over-activation of fibrogenic pathways (such as TGF-beta and mTORC1 signaling) impair the quality of wound healing and prevent functional tissue regeneration.
Ryoichi Mori, Tanya J. Shaw, Paul Martin. Molecular mechanisms linking wound inflammation and fibrosis: knockdown of osteopontin leads to rapid repair and reduced scarring. 2008. https://doi.org/10.1084/jem.20071412
Demonstrates that blocking inflammation-associated osteopontin reduces excessive scarring and accelerates normal tissue repair.
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Kenneth R. Cutroneo. TGF‐β–induced fibrosis and SMAD signaling: oligo decoys as natural therapeutics for inhibition of tissue fibrosis and scarring. 2007. https://doi.org/10.1111/j.1524-475x.2007.00226.x
Indicates that persistent TGF-beta activity drives excessive fibrosis, leading to impaired tissue structure and organ malfunction.
Wu M, Zhang J, Xiong N, Ma Y, Yong L, Liu H, Guo Q. Exosomes in Hypertrophic Scars and Keloids: Mechanisms and Therapeutic Potentials-A Narrative Review.. 2026. https://doi.org/10.1111/jocd.70705
Notes that pathological scars arise from dysregulated wound healing marked by excessive extracellular matrix deposition and abnormal fibroblast activation.
Dou H, Li J, Lin L, Jin M, Wang J, Fu H, Lu J, Chen Q, Xiang L, Wang J, Ding X. 4E-BP1 acts as a molecular rheostat balancing regenerative healing and fibrotic scarring.. 2026. https://doi.org/10.1038/s12276-026-01724-0
Shows that the mTORC1 effector 4E-BP1 balances reparative efficiency and fibrotic remodeling, where unchecked signaling promotes excessive collagen deposition.
Que H, Wang Y, Pan J, Yan Z. [The mechanism and research progress of thymic stromal lymphopoietin in chronic wound fibrosis].. 2026. https://europepmc.org/article/MED/42463317
Explains that while moderate fibrosis protects a wound, excessive fibrosis leads to pathological scarring that impedes complete healing.
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