Abstract
Posttraumatic fibrotic scarring is a significant medical problem that alters the proper functioning of injured tissues. Current methods to reduce posttraumatic fibrosis rely on anti-inflammatory and anti-proliferative agents with broad intracellular targets. As a result, their use is not fully effective and may cause unwanted side effects. Our group previously demonstrated that extracellular collagen fibrillogenesis is a valid and specific target to reduce collagen-rich scar buildup. Our previous studies showed that a rationally designed antibody that binds the C-terminal telopeptide of the α2(I) chain involved in the aggregation of collagen molecules limits fibril assembly in vitro and reduces scar formation in vivo. Here, we have utilized a clinically relevant arthrofibrosis model to study the broad mechanisms of the anti-scarring activity of this antibody. Moreover, we analyzed the effects of targeting collagen fibril formation on the quality of healed joint tissues, including the posterior capsule, patellar tendon, and subchondral bone. Our results show that blocking collagen fibrillogenesis not only reduces collagen content in the scar, but also accelerates the remodeling of healing tissues and changes the collagen fibrils’ cross-linking. In total, this study demonstrated that targeting collagen fibrillogenesis to limit arthrofibrosis affects neither the quality of healing of the joint tissues nor disturbs vital tissues and organs.
Funder
U.S. Department of Defense
Publisher
Public Library of Science (PLoS)
Reference71 articles.
1. Renal epithelial injury and fibrosis;B Kaissling;Biochim Biophys Acta,2013
2. Fibrosis following Acute Skeletal Muscle Injury: Mitigation and Reversal Potential in the Clinic;T Gardner;J Sports Med (Hindawi Publ Corp),2020
3. Arthrofibrosis and large joint scarring;AF Chen;Connect Tissue Res,2019
4. Fibrosis is a common outcome following total knee arthroplasty;N Abdul;Scientific reports,2015
5. Keloid and Hypertrophic Scar Formation, Prevention, and Management: Standard Review of Abnormal Scarring in Orthopaedic Surgery;G Grabowski;The Journal of the American Academy of Orthopaedic Surgeons,2020
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