HYPERMED DELAYED FRACTURE REPAIR & FRACTURE NON UNION

Delayed Fracture Repair

 

What Are the Advantages of Hyperbaric Oxygenation for delayed Fracture Repair?

HBOT targets ‘zones of ischemia’ (areas of tissue and bone with retarded blood supply and nutritional status), facilitating new capillary network support and increasing blood supply (neovascularisation) by increasing vascular stem cell mobilization growth factors, reducing painful swelling and inflammation and promoting metabolism and immune system responses overcoming underlying infectious agents.

Further review - Hypoxic Induced Apoptosis.

Hyperbaric oxygen therapy in extremity trauma.

J Am Acad Orthop Surg. 2004 Nov-Dec;12(6):376-84.

Greensmith JE. St Elizabeth Hospital, Appleton, WI 54915, USA.

Abstract

Hyperbaric oxygen therapy potentially can provide enhanced oxygen delivery to peripheral tissues affected by vascular disruption, cytogenic and vasogenic edema, and cellular hypoxia caused by extremity trauma. After appropriate resuscitation, macrovascular repair, and fracture fixation/stabilization, adjunctive hyperbaric oxygen therapy can enhance tissue oxygen content. In patients with crush injury or early compartment syndrome, hyperbaric oxygen therapy may reduce the penumbra of cells at risk for delayed necrosis and secondary ischemia. Animal experiments and human case series suggest the benefits of such therapy, and recent randomized, prospective studies on trauma patients have confirmed its efficacy in those with extremity trauma. However, more data are necessary to determine additional indications as well as optimal timing and dosing for hyperbaric oxygen therapy.

Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy.

Thom SR, Milovanova TN, Yang M, Bhopale VM, Sorokina EM, Uzun G, Malay DS, Troiano MA, Hardy KR, Lambert DS, Logue CJ, Margolis DJ. Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6068, USA. sthom@mail.med.upenn.edu

Abstract

Diabetic patients undergoing hyperbaric oxygen therapies (HBO(2)T) for refractory lower extremity neuropathic ulcers exhibit more than a twofold elevation (p=0.004) in circulating stem cells after treatments and the post-HBO(2)T CD34(+) cell population contains two- to threefold higher levels of hypoxia inducible factors-1, -2, and -3, as well as thioredoxin-1 (p<0.003), than cells present in blood before HBO(2)T. Skin margins obtained from 2-day-old abdominal wounds exhibit higher expression of CD133, CD34, hypoxia inducible factor-1, and Trx-1 vs. margins from refractory lower extremity wounds and expression of these proteins in all wounds is increased due to HBO(2)T (p<0.003). HBO(2)T is known to mobilize bone marrow stem cells by stimulating nitric oxide synthase. We found that nitric oxide synthase activity is acutely increased in patients' platelets following HBO(2)T and remains elevated for at least 20 hours. We conclude that HBO(2) T stimulates vasculogenic stem cell mobilization from bone marrow of diabetics and more cells are recruited to skin wounds.

Hyperbaric oxygen induces placental growth factor expression in bone marrow-derived mesenchymal stem cells.

Shyu KG, Hung HF, Wang BW, Chang H. Life Sci. 2008 Jul 4;83(1-2):65-73. Epub 2008 May 23.

Source

Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, and Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Abstract

The bone marrow is home to mesenchymal stem cells (MSCs) that are able to differentiate into many different cell types. The effect of hyperbaric oxygen (HBO) on MSCs is poorly understood. Placental growth factor (PlGF) is an attractive therapeutic agent for stimulating revascularization of ischemic tissue. HBO has been shown to improve diabetic wound healing by increase circulating stem cells. We hypothesized that HBO induces PlGF expression in bone marrow-derived MSCs. The MSCs were obtained from adult human bone marrow and expanded in vitro. The purity and characteristics of MSCs were identified by flow cytometry and immunophenotyping. HBO at 2.5 ATA (atmosphere absolute) significantly increased PlGF protein and mRNA expression. The induction of PlGF protein by HBO was significantly blocked by the addition of N-acetylcysteine, while wortmannin, PD98059, SP600125 and SB203580 had no effect on PlGF protein expression. However, the specific inhibitor of nitric oxide synthase, L-NAME did not alter the PlGF protein expression induced by HBO. HBO significantly increased the reactive oxygen species production and pretreatment with N-acetylcysteine significantly blocked the induction of reactive oxygen species by HBO. HBO significantly increased the migration and tube formation of MSCs and pretreatment with N-acetylcysteine and PlGF siRNA significantly blocked the induction of migration and tube formation by HBO. In conclusion, HBO induced the expression of PlGF in human bone marrow-derived MSCs at least through the oxidative stress-related pathways, which may play an important role in HBO-induced vasculogenesis

Hyperbaric oxygen results in increased vascular endothelial growth factor (VEGF) protein expression

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Apr;105(4):417-22. Epub 2008 Feb 21.

Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada.

Abstract

Hyperbaric oxygen therapy (HBO) promotes osseous healing, however the mechanism by which this occurs has not been elucidated. HBO may promote angiogenesis, which is vital for bone healing. Vascular endothelial growth factor (VEGF) is one of the key factors that stimulates angiogenesis.

The objective of this study was to investigate whether HBO altered VEGF expression during bone healing.

Archived samples from calvarial defects of rabbits exposed to HBO (2.4 ATA, 90 minutes a day, 5 days a week for 4 weeks) and normobaric oxygen controls (NBO) were analyzed by immunohistochemistry.

VEGF expression in 6-week HBO samples was elevated compared to NBO (P = .012). Staining of the 12-week HBO samples was reduced compared to 6-week HBO (P = .008) and was similar to 6- and 12-week NBO control samples.

HBO therapy resulted in increased VEGF expression in the defects even 2 weeks after the termination of treatment (6 weeks postsurgery).