Abstract
Healing of an anterior cruciate ligament graft in bone tunnel yields weaker fibrous scar tissue, which may prolong an already prolonged healing process within the tendon–bone interface. In this study, gelatin molecules were added to thermosensitive chitosan/β-glycerol phosphate disodium salt hydrogels to form chitosan/gelatin/β-glycerol phosphate (C/G/GP) hydrogels, which were applied to 0.1 mg/mL collagenase carrier in the tendon–bone junction. New Zealand white rabbit’s long digital extensor tendon was detached and translated into a 2.5-mm diameter tibial plateau tunnel. Thirty-six rabbits underwent bilateral surgery and hydrogel injection treatment with and without collagenase. Histological analyses revealed early healing and more bone formation at the tendon–bone interface after collagenase partial digestion. The area of metachromasia significantly increased in both 4-week and 8-week groups after collagenase treatment (p < 0.01). Micro computed tomography showed a significant increase in total bone volume and bone volume/tissue volume in the 8 weeks after collagenase treatment, compared with the control group. Load-to-failure was significantly higher in the treated group at 8 weeks (23.8 ± 8.13 N vs 14.3 ± 3.9 N; p = 0.008). Treatment with collagenase digestion resulted in a 66% increase in pull-out strength. In conclusion, injection of C/G/GP hydrogel with collagenase improves tendon-to-bone healing in a rabbit model.
Highlights
The anterior cruciate ligament (ACL) is one of the most commonly injured soft tissue structures, with an injury incidence of one in 3000 in the American population [1]
We aimed to investigate the effects of low dose collagenase for partial digestion of the extracellular matrix (ECM) in improving tendon–bone healing
There is no significant difference between the chitosan/gelatin/β-glycerol phosphate (C/G/glycerol phosphate (GP)) hydrogels with or without collagenase, compared with the monolayer cultured group (n = 5, p> 0.05)
Summary
The anterior cruciate ligament (ACL) is one of the most commonly injured soft tissue structures, with an injury incidence of one in 3000 in the American population [1]. Primary repair is not effective for treating injured ACL tissue due to poor healing potential. ACL reconstruction with autografts or allografts has a greater than 90% success rate in restoring knee stability or previous functional. Autologous bone-patellar-tendon grafts (BPTB) achieve good results due to direct bone-to-bone healing in femoral and tibial tunnels. The harvesting of BPTB results in significant donor morbidity, anterior knee pain, and higher rates of osteoarthritis [3]. Autologous hamstring tendon grafts restore function to a similar extent as BPTB grafts, but have a higher graft failure rate and revision rate [4,5]. There is an unmet need for interventions that can enhance tendon-to-bone healing to attain a lower graft failure rate and better functional outcomes
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