Nerve regeneration during patellar tendon autograft remodelling after anterior cruciate ligament reconstruction: An experimental and clinical study

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Abstract
The innervation of the rat and human anterior cruciate ligament, patellar tendon, and patellar tendon autograft after reconstruction of the anterior cruciate ligament was investigated by immunohistochemical and histological methods. A rat model of reconstruction with patellar tendon autograft was evaluated during active graft remodelling (2–16 weeks) and compared with normal ligament and tendon. The knees of 10 patients who had undergone reconstruction with patellar tendon autograft were examined 5–37 months postoperatively (remodelling fully completed) with arthroscopy and biopsy. As a control, biopsies from normal ligament and tendon were obtained from four patients. Nerve fibers were identified using antisera for protein gene product 9.5, a general neural marker. Neuronal regeneration was assessed by the expression of growth-associated protein 43/B-50. The sensory type of innervation was characterized by assessing the distribution of nerves containing the sensory neuropeptides calcitonin gene related peptide and substance P. Immunoreactivity for all neural markers was found in both rat and human anterior cruciate ligament and patellar tendon. Two weeks after reconstruction, the rat autograft was acellular and no innervation could be identified. After 4 weeks, the grafts were viable, and immunoreactivity for protein gene product 9.5, growth associated protein 43/B-50, and calcitonin gene-related peptide was found until the 16th week postoperatively. Immunoreactivity for substance P was found in rat autografts at 4 weeks postoperatively only. All biopsies of human patellar tendon autograft showed signs of the remodelling process being fully completed, with revascularization and a sinusoidal collagen pattern with fibroblast repopulation. Neuropeptide immunoreactivity, however, was not found. The presence of immunoreactivity to sensory neuropeptides in the anterior cruciate ligament and patellar tendon may indicate a nociceptive and neuromodulatory function of these structures. The expression of sensory neuropeptides in the rat patellar tendon autograft suggests a possible involvement of sensory innervation during healing of the graft.