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.
Highlights
Balanced scar formation is crucial to natural wound healing [1]
To reduce the number of collagen fibrils formed in response to injury, we developed a monoclonal anti-collagen antibody (ACA) that targets the C-terminal telopeptide of the α2(I) chain (α2Ct), which is engaged in the aggregation of collagen monomers into fibrils [11, 13, 14]
Surgical and accidental injuries to articular joints may lead to arthrofibrosis
Summary
Balanced scar formation is crucial to natural wound healing [1]. When scarring is excessive, it negatively impacts the vital functions of the affected tissues. Fibrotic scars formed in muscles weaken them, and the scar tissue formed within and around injured joints causes arthrofibrosis [2, 3]. Arthrofibrosis, which can occur due to accidental trauma or surgery, stiffens the joints, restricts the ability to perform activities of daily living, and causes pain [4].
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