The early effect of high molecular weight hyaluronan (hyaluronic acid) on anterior cruciate ligament healing: An experimental study in rabbits

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Abstract
The purpose of this study was to assess, morphologically and biochemically, the effect of hyaluronan (HA) on the early repair process of the anterior cruciate ligament (ACL). Following partial bilateral laceration in the midsubstance of the cruciate ligament, a single dose of HA (MW of 3.6 × 106) was injected in one knee and saline in the contralateral knee. Postsurgery, the rabbits were allowed normal (nonimmobilized) cage activity, and were killed after 4 (n = 11) and 12 (n = 10) weeks. The ligaments were evaluated by gross morphology and graded according to the degree of repair. We used grades 1, 2, and 3 for uncovered, partially covered, and totally covered lacerations, respectively. Five of the HA-treated ligaments at each time studied were completely covered, compared to 0 at 4 weeks, and 1 at 12 weeks in the saline group. Paired evaluations of the lacerated ACLs showed that the HA-treated ligaments received a healing grade higher than the ligaments exposed to saline in 14 of the 21 animals. In the remaining animals, there was no difference between the sides. The repaired tissue of the ACLs was also examined by light and electron microscopy. When compared qualitatively with saline controls, HA-treated ligaments exhibited a more pronounced repair, with an increased angiogenesis and less inflammatory response. Biochemical analysis demonstrated a mean higher value of type III collagen in the HA-treated injured ACL than in saline-treated injured ACL (13.4 ± 1.1% and 11.0 ± 0.8%, respectively). This increased synthesis of type III collagen in the HA-treated injured ACL was statistically higher (p < 0.05) when compared to the saline-treated injured ACL.