Effects of hyperbaric oxygen therapy on bone, muscle, cartilage, tendon and ligaments in animal studies: a systematic review

Abstract

Hyperbaric oxygen therapy (HBOT) has been investigated for its potential to enhance tissue healing because of its capacity to increase oxygen tension in ischemic and hypoxic tissues. Numerous preclinical studies have explored its role in the repair and regeneration of different musculoskeletal tissues. The aim of this systematic review was to assess the effects of HBOT on bone, muscle, cartilage, tendon, and ligament tissue in preclinical studies. Systematic review. A systematic review was performed via PubMed and LIVIVO databases. The inclusion criteria were experimental animal studies investigating the effects of HBOT on musculoskeletal tissues between 1996 and 2025 without the use of other therapeutics. Data on the study concept; animal models; tissue type; and macroscopic, histological, immunohistochemical, clinical, radiological and biomechanical effects of HBOT were extracted. The results were synthesized descriptively, grouped by tissue type to investigate tissue-modifying effects in preclinical animal studies. Risk of bias was assessed using SYRCLE’s Risk of Bias Tool. The systematic review was not prospectively registered. A total of 37 studies involving 2141 animals, e.g., rodents, rabbits, and larger mammals, were included in this review. Seventeen studies reported on muscle tissue,12 on tendons and ligaments, 6 on bone tissue and two on cartilage. Findings varied substantially by tissue type, injury model, and outcome domain. Histological and molecular outcomes were described more frequently to have improved than biomechanical ones. Ischaemia-reperfusion muscle models showed largely heterogenous findings, contusion models showed positive signals. Bone distraction osteogenesis showed the most consistent HBOT effects in biomechanical outcomes. Tendon and ligament reconstruction models showed promising histological and biomechanical outcomes in more methodologically robust studies. The risk of bias was high or unclear in most studies, with consistent shortcomings in randomization, blinding, and allocation concealment limiting confidence of the reported outcomes. Adverse effects of HBOT on the reviewed tissues have not been reported throughout studies, barotrauma has been mentioned as a possible side effect in few cases. HBOT protocols varied widely throughout all studies from 1 to 56 HBOT sessions. Preclinical evidence suggests that HBOT may support early-phase repair of musculoskeletal tissues, though findings showed inconsistencies in outcomes with many studies having high and unclear risk of bias, insufficient to support definitive conclusions. This highlights the need for standardized protocols and controlled clinical trials to determine optimal treatment parameters as well as transferability into clinical practice before certain translational recommendations can be made. Although this is a basic science review, understanding the effect of HBOT on healing of bone, muscle, ligament, tendon and cartilage tissue in animal models is clinically relevant for evaluating its translational potential in treating sport-related orthopedic injury healing in humans.