The Effect of Combining Hyaluronic Acid and Human Dermal Fibroblasts on Tendon Healing

Abstract

Background: The incidence of rotator cuff tears is rapidly increasing, and operative techniques for rotator cuff repair have been developed. However, the rates of postoperative retear remain high. Purpose/Hypothesis: The purpose was to determine the effects of human dermal fibroblasts (HDFs) with hyaluronic acid (HA) on tendon-to-bone healing in a rabbit model of chronic rotator cuff tear injury. It was hypothesized that HA would enhance HDF proliferation and that a combination of HA and HDFs would produce a synergistic effect on the healing of repaired rotator cuff tendons of rabbits. Study Design: Controlled laboratory study. Methods: For in vitro study, HDFs were plated on a 24-well plate. After 1 day, 2 wells were designated as the test group and treated with 0.75% HA in phenol red–free Dulbecco's modified Eagle medium (DMEM). An other 2 wells served as control groups and were treated with the same volume of phenol red–free DMEM without HA. Each group was duplicated, resulting in a total of 4 wells, with 2 wells in each group for replication purposes. The cells were incubated for 24 hours, followed by 72-hour cultivation. Absorbance ratios at 96 and 24 hours were compared to evaluate cell proliferation. For the in vivo study, a total of 24 rabbits were randomly allocated to groups A, B, and C (n = 8 each). Supraspinatus tendons were detached bilaterally and left for 6 weeks to establish a chronic rotator tear model. Torn tendons were subsequently repaired using the following injections: group A, 0.5 × 106 HDFs with HA; group B, HA only; and group C, saline only. At 12 weeks after repair, biomechanical tests and histological evaluation were performed. Results: In vitro study showed that HDF proliferation significantly increased with HA (HDFs with HA vs HDFs without HA; 3.96 ± 0.09 vs 2.53 ± 0.15; P < .01). In vivo, group A showed significantly higher load-to-failure values than the other groups (53.8 ± 6.9 N/kg for group A, 30.6 ± 6.4 N/kg for group B, and 24.3 ± 7.6 N/kg for group C; P < .001). Histological evaluation confirmed that group A showed higher collagen fiber density and better collagen fiber continuity, tendon-to-bone interface maturation, and nuclear shape than the other groups (all P < .05). Conclusion: This controlled laboratory study verified the potential of the combination of HDFs and HA in enhancing healing in a chronic rotator cuff tear rabbit model. Clinical Relevance: A potential synergistic effect on rotator cuff tendon healing may be expected from a combination of HDFs and HA.