Scarless healing in the fetus: Implications and strategies for postnatal tendon repair.

摘要

Tendon injuries are a common clinical problem and their resolution is often hampered by adhesions and scarring, which restrict joint movement and compromise function. In contrast to adult tissue repair, extensive experimental evidence exists that fetal tissues, including skin, cartilage and bone, heal in the absence of scar formation. More recently, our research has demonstrated that fetal tendon is also capable of healing scarlessly; however, whether this capability is intrinsic to the fetal tendon itself or the result of its unique environment was not known. Nor had any previous attempts been made to utilize the information learned from fetal wound healing studies to treat adult tendon injuries. Therefore, we developed a model to assess the effect of environment on fetal tendon healing. We next designed a device to facilitate the transition of our studies to a smaller animal model; which was then used to investigate postnatal tendon repair strategies. In the first stage of this work, we hypothesized that injured fetal tendon tissue transplanted into an adult environment would heal regeneratively. Our results supported this hypothesis, with histological and biomechanical analyses revealing considerable alterations in adult tendon transplants after injury while fetal transplants showed no abnormalities. Our second objective was to improve upon our method of measuring the cross-sectional area of small connective tissues. To accomplish this, we utilized a laser triangulation sensor, which determines position by measuring reflected light from the target surface; the accuracy and repeatability of the system were demonstrated. Lastly, based on the large body of evidence implicating HA-receptor interactions in the processes of inflammation and scarring, along with observations from fetal skin studies, our third objective was to analyze the effects of globally inhibiting HA-receptor interactions in injured patellar tendons. We hypothesized that tendons of mice treated with a peptide inhibiting these interactions would exhibit superior healing properties, as measured by the inflammatory response, mechanical properties and fiber organization of the injured tissue. Contrary to our expectations, our treatment had little effect on the overall outcome. While surprising, these results may indicate a more complex role for HA in tendon healing deserving of further investigation.