Studies in Fetal Wound Healing IV. Hyaluronic Acid-Stimulating Activity Distinguishes Fetal Wound Fluid from Adult Wound Fluid

Abstract

Recent clinical and experimental evidence suggests that the fetus responds to injury in a fashion fundamentally different from that of the adult. Our initial experience with human open fetal surgery reinforces experimental observations that the fetal wounds heal without the scarring, inflammation, and contraction that often accompany adult wounds. In this study we examine fetal wound fluid in an attempt to elucidate the control mechanisms that endow the fetus with unique healing properties. The extracellular matrix of fetal wounds is rich in hyaluronic acid, a glycosaminoglycan found in high concentrations whenever there is tissue proliferation, regeneration, and repair. We establish that wound fluid from the fetus contains high levels of hyaluronic acid-stimulating activity that may underlie the elevated deposition of hyaluronic acid in the fetal wound matrix. In contrast there was no hyaluronic acid-stimulating activity present in adult wound fluid. Hyaluronic acid, in turn, fosters an extracellular environment permissive for cell motility and proliferation that may account for the unique properties observed in fetal wound healing.

Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation

“…A reasonable approach to investigate this enigma is to compare adult and fetal healing in as many respects as possible. Thus it was recently recognized that the time pattern for the increased HYA concentration in the wound was substantially different in fetal and in adult wounds [42,43]. The fetal wound was thus characterized by a considerable amount of 'hyaluronic acid stimulating activity' (HASA), a long-standing presence of HYA in the wound bed and an absence of hyaluronidase activity.…”

The Extracellular Matrix of the Fetal Wound: Hyaluronic Acid Controls Lymphocyte Adhesion

“…Extensive wound healing research has clearly documented the remarkable characteristics of fetal tissue repair following injury [1][2][3][4][5][6][7][8][9][10]. Perhaps the most striking aspect of these investigations has been the finding that fetal wounds heal without an inflammatory response and generate a "scarless" repair marked by tissue regeneration and organized structural integrity rather than be an important factor in thi~ procese of scarless ,repair [11][12][13].…”

Effects of repetitive injections of hyaluronic acid on peritendinous adhesions after flexor tendon repair: a preliminary randomized, placebo-controlled clinical trial

“…[31] HA provides a healing process through regeneration and growth rather than scarring and fibrosis. [21,22] However, this effect has been variable. [32] The molecular weight and the concentration of the preparation are critical to its potential beneficial effects.…”

“…This macromolecular network would prevent fibrous ingrowth from the surrounding tissues. [21][22][23] The other explanation was that HA, being an effective soft tissue lubricant, might decrease the new extracellular matrix formation due to the inhibition of mononuclear phagocytes and lymphocytes. [24] The goal of this clinical study was to compare the effects of repetitive injections of HA with placebo on the functional outcome after primary digital zone-II flexor tendon repair.…”