Revisiting the role of hyperbaric oxygen therapy in knee injuries: Potential benefits and mechanisms

Abstract

Knee injury negatively impacts routine activities and quality of life of millions of people every year. Disruption of tendons, ligaments, and articular cartilage are major causes of knee lesions, leading to social and economic losses. Besides the attempts for an optimal recovery of knee function after surgery, the joint healing process is not always adequate given the nature of intra-articular environment. Based on that, different therapeutic methods attempt to improve healing capacity. Hyperbaric oxygen therapy (HBOT) is an innovative biophysical approach that can be used as an adjuvant treatment post-knee surgery, to potentially prevent chronic disorders that commonly follows knee injuries. Given the well-recognized role of HBOT in improving wound healing, further research is necessary to clarify the benefits of HBOT in damaged musculoskeletal tissues, especially knee disorders. Here, we review important mechanisms of action for HBOT-induced healing including the induction of angiogenesis, modulation of inflammation and extracellular matrix components, and activation of parenchyma cells-key events to restore knee function after injury. This review discusses the basic science of the healing process in knee injuries, the role of oxygen during cicatrization, and shed light on the promising actions of HBOT in treating knee disorders, such as tendon, ligament, and cartilage injuries.

Scaffolds with high oxygen content support osteogenic cell survival under hypoxia

“…Since optimal O 2 level is essential for cellular metabolism and proliferation and plays a crucial role in the healing process, 29 a sustained release of O 2 from scaffolds can promote bone regeneration and expedite the recovery process under limited supply of O 2 . 30–33…”

Hyperbaric oxygen therapy enhances graft healing and mechanical properties after anterior cruciate ligament reconstruction: An experimental study in rabbits

“…This allows oxygen to diffuse over a greater distance from the capillary to the healing area, supplying that area with the necessary oxygen to promote tissue repair. Additionally, HBOT regulates the production of reactive oxygen and nitrogen species, leading to a controlled oxidative stress state 24 . These reactive species generated by the “oxidative eustress” act as signaling mediators in several pathways, inducing the synthesis of growth factors and cytokines that will modulate the inflammatory response, promote neovascularization (via the production of VEGF, PDGF, and angiopoietin‐2), and regulate the ECM 11,15,65 .…”

“…These reactive species generated by the “oxidative eustress” act as signaling mediators in several pathways, inducing the synthesis of growth factors and cytokines that will modulate the inflammatory response, promote neovascularization (via the production of VEGF, PDGF, and angiopoietin‐2), and regulate the ECM 11,15,65 . Preclinical and clinical studies have investigated how hyperbaric oxygenation may favor knee ligament cicatrization 24 . In this regard, HBOT has been shown to stimulate fibroblastic synthesis of collagen, mostly collagen type I, increase the concentration of tissue inhibitors of metalloproteinases (TIMPs), and promote graft vascularization and osteointegration 12,16–18,66,67 .…”

“…Preclinical and clinical studies have demonstrated a range of benefits of HBOT, including modulation of the inflammatory response, neovascularization, collagen synthesis, and extracellular matrix (ECM) regulation 15–23 . These processes play a crucial role during wound repair and may be essential for a successful ACL reconstruction 21,24 …”

“…Enhancing graft healing after ACL reconstruction is imperative to reduce surgical failures and avoid adverse outcomes. Despite the limited information regarding the role of HBOT in ligament injuries, the substantial evidence supporting HBOT's effectiveness in wound healing and other musculoskeletal injuries encourages its investigation in the context of ACL reconstruction 24 . The aim of this study was to evaluate the effect of HBOT on graft healing after ACL reconstruction.…”