Skip to main content
Top
Published in: BMC Oral Health 1/2023

Open Access 01-12-2023 | Diabetes | Research

Hyperbaric oxygen therapy efficacy on mandibular defect regeneration in rats with diabetes mellitus: an animal study

Authors: Rodina H. Eldisoky, Salwa A. Younes, Samia S. Omar, Hagar S. Gharib, Tarek A. Tamara

Published in: BMC Oral Health | Issue 1/2023

Login to get access

Abstract

Background

This study aimed to investigate the influence of hyperbaric oxygen therapy on mandibular critical-sized defect regeneration in rats with experimentally induced type I diabetes mellitus. Restoration of large osseous defects in an impaired osteogenic condition such as diabetes mellitus is a challenging task in clinical practice. Therefore, investigating adjunctive therapies to accelerate the regeneration of such defects is crucial.

Materials and methods

Sixteen albino rats were divided into two groups (n = 8/group). To induce diabetes mellitus, a single streptozotocin dosage was injected. Critical-sized defects were created in the right posterior mandibles and filled with beta-tricalcium phosphate graft. The study group was subjected to 90-min sessions of hyperbaric oxygen at 2.4 ATA, for 5 consecutive days per week. Euthanasia was carried out after 3 weeks of therapy. Bone regeneration was examined histologically and histomorphometrically. Angiogenesis was assessed by immunohistochemistry against vascular endothelial progenitor cell marker (CD34) and the microvessel density was calculated.

Results

Exposure of diabetic animals to hyperbaric oxygen resulted in superior bone regeneration and increased endothelial cell proliferation, which were revealed histologically and immunohistochemically, respectively. These results were confirmed by histomorphometric analysis which disclosed a higher percentage of new bone surface area and microvessel density in the study group.

Conclusions

Hyperbaric oxygen has a beneficial effect on bone regenerative capacity, qualitatively and quantitively, as well as the ability to stimulate angiogenesis.
Literature
1.
go back to reference Weaver LK. Hyperbaric oxygen therapy indications. 13th ed. North Palm Beach: Best Publishing Company; 2014. Weaver LK. Hyperbaric oxygen therapy indications. 13th ed. North Palm Beach: Best Publishing Company; 2014.
2.
go back to reference Ortega MA, Fraile-Martinez O, Monserrat J, García-Montero C, García-Honduvilla N, Canals ML, et al. A general overview on the hyperbaric oxygen therapy: applications, mechanisms and translational opportunities. Medicina (Kaunas). 2021;57:864.PubMedCrossRef Ortega MA, Fraile-Martinez O, Monserrat J, García-Montero C, García-Honduvilla N, Canals ML, et al. A general overview on the hyperbaric oxygen therapy: applications, mechanisms and translational opportunities. Medicina (Kaunas). 2021;57:864.PubMedCrossRef
3.
go back to reference Özkan E, Bereket MC, Önger ME, Polat AV. The effect of unfocused extracorporeal shock wave therapy on bone defect healing in diabetics. J Craniofac Surg. 2018;29:1081–6.PubMedCrossRef Özkan E, Bereket MC, Önger ME, Polat AV. The effect of unfocused extracorporeal shock wave therapy on bone defect healing in diabetics. J Craniofac Surg. 2018;29:1081–6.PubMedCrossRef
4.
go back to reference Kahle AC, Cooper JS. Hyperbaric physiological and pharmacological effects of gases. Treasure Island: StatPearls Publishing; 2022. Kahle AC, Cooper JS. Hyperbaric physiological and pharmacological effects of gases. Treasure Island: StatPearls Publishing; 2022.
5.
go back to reference Svalestad J, Thorsen E, Vaagbø G, Hellem S. Effect of hyperbaric oxygen treatment on oxygen tension and vascular capacity in irradiated skin and mucosa. Int J Oral Maxillofac Surg. 2014;43:107–12.PubMedCrossRef Svalestad J, Thorsen E, Vaagbø G, Hellem S. Effect of hyperbaric oxygen treatment on oxygen tension and vascular capacity in irradiated skin and mucosa. Int J Oral Maxillofac Surg. 2014;43:107–12.PubMedCrossRef
6.
go back to reference Sheikh AY, Gibson JJ, Rollins MD, Hopf HW, Hussain Z, Hunt TK. Effect of hyperoxia on vascular endothelial growth factor levels in a wound model. Arch Surg. 2000;135:1293–7.PubMedCrossRef Sheikh AY, Gibson JJ, Rollins MD, Hopf HW, Hussain Z, Hunt TK. Effect of hyperoxia on vascular endothelial growth factor levels in a wound model. Arch Surg. 2000;135:1293–7.PubMedCrossRef
7.
go back to reference Fok TC, Jan A, Peel SA, Evans AW, Clokie CM, Sándor GK. Hyperbaric oxygen results in increased vascular endothelial growth factor (VEGF) protein expression in rabbit calvarial critical-sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105:417–22.PubMedCrossRef Fok TC, Jan A, Peel SA, Evans AW, Clokie CM, Sándor GK. Hyperbaric oxygen results in increased vascular endothelial growth factor (VEGF) protein expression in rabbit calvarial critical-sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105:417–22.PubMedCrossRef
8.
go back to reference Goldstein LJ, Gallagher KA, Bauer SM, Bauer RJ, Baireddy V, Liu ZJ, et al. Endothelial progenitor cell release into circulation is triggered by hyperoxia-induced increases in bone marrow nitric oxide. Stem Cells. 2006;24:2309–18.PubMedCrossRef Goldstein LJ, Gallagher KA, Bauer SM, Bauer RJ, Baireddy V, Liu ZJ, et al. Endothelial progenitor cell release into circulation is triggered by hyperoxia-induced increases in bone marrow nitric oxide. Stem Cells. 2006;24:2309–18.PubMedCrossRef
9.
go back to reference Lin PY, Sung PH, Chung SY, Hsu SL, Chung WJ, Sheu JJ, et al. Hyperbaric oxygen therapy enhanced circulating levels of endothelial progenitor cells and angiogenesis biomarkers, blood flow, in ischemic areas in patients with peripheral arterial occlusive disease. J Clin Med. 2018;7:548.PubMedPubMedCentralCrossRef Lin PY, Sung PH, Chung SY, Hsu SL, Chung WJ, Sheu JJ, et al. Hyperbaric oxygen therapy enhanced circulating levels of endothelial progenitor cells and angiogenesis biomarkers, blood flow, in ischemic areas in patients with peripheral arterial occlusive disease. J Clin Med. 2018;7:548.PubMedPubMedCentralCrossRef
10.
go back to reference Wu D, Malda J, Crawford R, Xiao Y. Effects of hyperbaric oxygen on proliferation and differentiation of osteoblasts from human alveolar bone. Connect Tissue Res. 2007;48:206–13.PubMedCrossRef Wu D, Malda J, Crawford R, Xiao Y. Effects of hyperbaric oxygen on proliferation and differentiation of osteoblasts from human alveolar bone. Connect Tissue Res. 2007;48:206–13.PubMedCrossRef
11.
go back to reference Al Hadi H, Smerdon GR, Fox SW. Hyperbaric oxygen therapy accelerates osteoblast differentiation and promotes bone formation. J Dent. 2015;43:382–8.PubMedCrossRef Al Hadi H, Smerdon GR, Fox SW. Hyperbaric oxygen therapy accelerates osteoblast differentiation and promotes bone formation. J Dent. 2015;43:382–8.PubMedCrossRef
12.
go back to reference Pedersen TO, Xing Z, Finne-Wistrand A, Hellem S, Mustafa K. Hyperbaric oxygen stimulates vascularization and bone formation in rat calvarial defects. Int J Oral Maxillofac Surg. 2013;42:907–14.PubMedCrossRef Pedersen TO, Xing Z, Finne-Wistrand A, Hellem S, Mustafa K. Hyperbaric oxygen stimulates vascularization and bone formation in rat calvarial defects. Int J Oral Maxillofac Surg. 2013;42:907–14.PubMedCrossRef
14.
go back to reference Abidia A, Laden G, Kuhan G, Johnson BF, Wilkinson AR, Renwick PM, et al. The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial. Eur J Vasc Endovasc Surg. 2003;25:513–8.PubMedCrossRef Abidia A, Laden G, Kuhan G, Johnson BF, Wilkinson AR, Renwick PM, et al. The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial. Eur J Vasc Endovasc Surg. 2003;25:513–8.PubMedCrossRef
15.
go back to reference Gurdol F, Cimsit M, Oner-Iyidogan Y, Kocak H, Sengun S, Yalcinkaya-Demirsoz S. Collagen synthesis, nitric oxide and asymmetric dimethylarginine in diabetic subjects undergoing hyperbaric oxygen therapy. Physiol Res. 2010;59:423–9.PubMedCrossRef Gurdol F, Cimsit M, Oner-Iyidogan Y, Kocak H, Sengun S, Yalcinkaya-Demirsoz S. Collagen synthesis, nitric oxide and asymmetric dimethylarginine in diabetic subjects undergoing hyperbaric oxygen therapy. Physiol Res. 2010;59:423–9.PubMedCrossRef
16.
17.
go back to reference Retzepi M, Donos N. The effect of diabetes mellitus on osseous healing. Clin Oral Implants Res. 2010;21:673–81.PubMedCrossRef Retzepi M, Donos N. The effect of diabetes mellitus on osseous healing. Clin Oral Implants Res. 2010;21:673–81.PubMedCrossRef
19.
go back to reference Verhaeghe J, van Herck E, Visser WJ, Suiker AM, Thomasset M, Einhorn TA, et al. Bone and mineral metabolism in BB rats with long-term diabetes. Decreased Bone Turnover Osteoporos Diabetes. 1990;39:477–82. Verhaeghe J, van Herck E, Visser WJ, Suiker AM, Thomasset M, Einhorn TA, et al. Bone and mineral metabolism in BB rats with long-term diabetes. Decreased Bone Turnover Osteoporos Diabetes. 1990;39:477–82.
20.
go back to reference Hazra S, Jarajapu YP, Stepps V, Caballero S, Thinschmidt JS, Sautina L, et al. Long-term type 1 diabetes influences haematopoietic stem cells by reducing vascular repair potential and increasing inflammatory monocyte generation in a murine model. Diabetologia. 2013;56:644–53.PubMedCrossRef Hazra S, Jarajapu YP, Stepps V, Caballero S, Thinschmidt JS, Sautina L, et al. Long-term type 1 diabetes influences haematopoietic stem cells by reducing vascular repair potential and increasing inflammatory monocyte generation in a murine model. Diabetologia. 2013;56:644–53.PubMedCrossRef
21.
go back to reference Roddy E, DeBaun MR, Daoud-Gray A, Yang YP, Gardner MJ. Treatment of critical-sized bone defects: clinical and tissue engineering perspectives. Eur J Orthop Surg Traumatol. 2018;28:351–62.PubMedCrossRef Roddy E, DeBaun MR, Daoud-Gray A, Yang YP, Gardner MJ. Treatment of critical-sized bone defects: clinical and tissue engineering perspectives. Eur J Orthop Surg Traumatol. 2018;28:351–62.PubMedCrossRef
22.
go back to reference Grassmann JP, Schneppendahl J, Hakimi AR, Herten M, Betsch M, Lögters TT, et al. Hyperbaric oxygen therapy improves angiogenesis and bone formation in critical sized diaphyseal defects. J Orthop Res. 2015;33:513–20.PubMedCrossRef Grassmann JP, Schneppendahl J, Hakimi AR, Herten M, Betsch M, Lögters TT, et al. Hyperbaric oxygen therapy improves angiogenesis and bone formation in critical sized diaphyseal defects. J Orthop Res. 2015;33:513–20.PubMedCrossRef
23.
go back to reference Bohner M, Santoni BLG, Döbelin N. β-tricalcium phosphate for bone substitution: synthesis and properties. Acta Biomater. 2020;113:23–41.PubMedCrossRef Bohner M, Santoni BLG, Döbelin N. β-tricalcium phosphate for bone substitution: synthesis and properties. Acta Biomater. 2020;113:23–41.PubMedCrossRef
24.
go back to reference Ana ID, Satria GAP, Dewi AH, Ardhani R. Bioceramics for clinical application in regenerative dentistry. Adv Exp Med Biol. 2018;1077:309–16.PubMedCrossRef Ana ID, Satria GAP, Dewi AH, Ardhani R. Bioceramics for clinical application in regenerative dentistry. Adv Exp Med Biol. 2018;1077:309–16.PubMedCrossRef
25.
go back to reference Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG. Animal research: reporting in vivo experiments—the ARRIVE guidelines. J Cereb Blood Flow Metab. 2011;31:991–3.PubMedPubMedCentralCrossRef Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG. Animal research: reporting in vivo experiments—the ARRIVE guidelines. J Cereb Blood Flow Metab. 2011;31:991–3.PubMedPubMedCentralCrossRef
26.
go back to reference Fish R, Danneman PJ, Brown M, Karas A. Anesthesia and analgesia in laboratory animals. 2nd ed. New York: Academic Press; 2011. Fish R, Danneman PJ, Brown M, Karas A. Anesthesia and analgesia in laboratory animals. 2nd ed. New York: Academic Press; 2011.
27.
go back to reference Furuhata M, Takayama T, Yamamoto T, Ozawa Y, Senoo M, Ozaki M, et al. Real-time assessment of guided bone regeneration in critical size mandibular bone defects in rats using collagen membranes with adjunct fibroblast growth factor-2. J Dent Sci. 2021;16:1170–81.PubMedPubMedCentralCrossRef Furuhata M, Takayama T, Yamamoto T, Ozawa Y, Senoo M, Ozaki M, et al. Real-time assessment of guided bone regeneration in critical size mandibular bone defects in rats using collagen membranes with adjunct fibroblast growth factor-2. J Dent Sci. 2021;16:1170–81.PubMedPubMedCentralCrossRef
28.
go back to reference Eleftheriadis E, Leventis MD, Tosios KI, Faratzis G, Titsinidis S, Eleftheriadi I, et al. Osteogenic activity of β-tricalcium phosphate in a hydroxyl sulphate matrix and demineralized bone matrix: a histological study in rabbit mandible. J Oral Sci. 2010;52:377–84.PubMedCrossRef Eleftheriadis E, Leventis MD, Tosios KI, Faratzis G, Titsinidis S, Eleftheriadi I, et al. Osteogenic activity of β-tricalcium phosphate in a hydroxyl sulphate matrix and demineralized bone matrix: a histological study in rabbit mandible. J Oral Sci. 2010;52:377–84.PubMedCrossRef
29.
go back to reference Jan A, Sándor GK, Brkovic BB, Peel S, Evans AW, Clokie CM. Effect of hyperbaric oxygen on grafted and nongrafted calvarial critical-sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107:157–63.PubMedCrossRef Jan A, Sándor GK, Brkovic BB, Peel S, Evans AW, Clokie CM. Effect of hyperbaric oxygen on grafted and nongrafted calvarial critical-sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107:157–63.PubMedCrossRef
30.
go back to reference American Veterinary Medical Association. AVMA guidelines for the euthanasia of animals. Anim Welf. 2020;22:412. American Veterinary Medical Association. AVMA guidelines for the euthanasia of animals. Anim Welf. 2020;22:412.
31.
go back to reference Fina L, Molgaard HV, Robertson D, Bradley NJ, Monaghan P, Delia D, et al. Expression of the CD34 gene in vascular endothelial cells. Blood. 1990;75:2417–26.PubMedCrossRef Fina L, Molgaard HV, Robertson D, Bradley NJ, Monaghan P, Delia D, et al. Expression of the CD34 gene in vascular endothelial cells. Blood. 1990;75:2417–26.PubMedCrossRef
32.
go back to reference Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N Engl J Med. 1991;324:1–8.PubMedCrossRef Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N Engl J Med. 1991;324:1–8.PubMedCrossRef
33.
go back to reference Mahendra A, Maclean AD. Available biological treatments for complex non-unions. Injury. 2007;38(Suppl 4):S7-12.PubMedCrossRef Mahendra A, Maclean AD. Available biological treatments for complex non-unions. Injury. 2007;38(Suppl 4):S7-12.PubMedCrossRef
34.
go back to reference Pokharel RK, Paudel S, Lakhey RB. Iliac crest bone graft harvesting: modified technique for reduction of complications. JNMA J Nepal Med Assoc. 2022;60:325–8.PubMedPubMedCentralCrossRef Pokharel RK, Paudel S, Lakhey RB. Iliac crest bone graft harvesting: modified technique for reduction of complications. JNMA J Nepal Med Assoc. 2022;60:325–8.PubMedPubMedCentralCrossRef
35.
go back to reference Dias PC, Limirio P, Linhares CRB, Bergamini ML, Rocha FS, Morais RB, et al. Hyperbaric oxygen therapy effects on bone regeneration in type 1 diabetes mellitus in rats. Connect Tissue Res. 2018;59:574–80.PubMedCrossRef Dias PC, Limirio P, Linhares CRB, Bergamini ML, Rocha FS, Morais RB, et al. Hyperbaric oxygen therapy effects on bone regeneration in type 1 diabetes mellitus in rats. Connect Tissue Res. 2018;59:574–80.PubMedCrossRef
36.
go back to reference Weinberg E, Maymon T, Moses O, Weinreb M. Streptozotocin-induced diabetes in rats diminishes the size of the osteoprogenitor pool in bone marrow. Diabetes Res Clin Pract. 2014;103:35–41.PubMedCrossRef Weinberg E, Maymon T, Moses O, Weinreb M. Streptozotocin-induced diabetes in rats diminishes the size of the osteoprogenitor pool in bone marrow. Diabetes Res Clin Pract. 2014;103:35–41.PubMedCrossRef
37.
go back to reference Limirio PHJO, da Rocha Junior HA, Morais RBD, Hiraki KRN, Balbi APC, Soares PBF, et al. Influence of hyperbaric oxygen on biomechanics and structural bone matrix in type 1 diabetes mellitus rats. PLoS ONE. 2018;13:e0191694.PubMedPubMedCentralCrossRef Limirio PHJO, da Rocha Junior HA, Morais RBD, Hiraki KRN, Balbi APC, Soares PBF, et al. Influence of hyperbaric oxygen on biomechanics and structural bone matrix in type 1 diabetes mellitus rats. PLoS ONE. 2018;13:e0191694.PubMedPubMedCentralCrossRef
38.
go back to reference Park KM, Kim C, Park W, Park YB, Chung MK, Kim S. Bone regeneration effect of hyperbaric oxygen therapy duration on calvarial defects in irradiated rats. Biomed Res Int. 2019;2019:9051713.PubMedPubMedCentralCrossRef Park KM, Kim C, Park W, Park YB, Chung MK, Kim S. Bone regeneration effect of hyperbaric oxygen therapy duration on calvarial defects in irradiated rats. Biomed Res Int. 2019;2019:9051713.PubMedPubMedCentralCrossRef
39.
go back to reference Gärtner V, Eigentler TK. Pathogenesis of diabetic macro- and microangiopathy. Clin Nephrol. 2008;70:1–9.PubMedCrossRef Gärtner V, Eigentler TK. Pathogenesis of diabetic macro- and microangiopathy. Clin Nephrol. 2008;70:1–9.PubMedCrossRef
40.
go back to reference Cramer C, Freisinger E, Jones RK, Slakey DP, Dupin CL, Newsome ER, et al. Persistent high glucose concentrations alter the regenerative potential of mesenchymal stem cells. Stem Cells Dev. 2010;19:1875–84.PubMedCrossRef Cramer C, Freisinger E, Jones RK, Slakey DP, Dupin CL, Newsome ER, et al. Persistent high glucose concentrations alter the regenerative potential of mesenchymal stem cells. Stem Cells Dev. 2010;19:1875–84.PubMedCrossRef
41.
go back to reference Larsen SA, Kassem M, Rattan SI. Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells. Chem Cent J. 2012;6:18.PubMedPubMedCentralCrossRef Larsen SA, Kassem M, Rattan SI. Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells. Chem Cent J. 2012;6:18.PubMedPubMedCentralCrossRef
42.
go back to reference Kim KA, Shin YJ, Akram M, Kim ES, Choi KW, Suh H, et al. High glucose condition induces autophagy in endothelial progenitor cells contributing to angiogenic impairment. Biol Pharm Bull. 2014;37:1248–52.PubMedCrossRef Kim KA, Shin YJ, Akram M, Kim ES, Choi KW, Suh H, et al. High glucose condition induces autophagy in endothelial progenitor cells contributing to angiogenic impairment. Biol Pharm Bull. 2014;37:1248–52.PubMedCrossRef
43.
go back to reference Yeh WL, Lin SS, Yuan LJ, Lee KF, Lee MY, Ueng SW. Effects of hyperbaric oxygen treatment on tendon graft and tendon-bone integration in bone tunnel: biochemical and histological analysis in rabbits. J Orthop Res. 2007;25:636–45.PubMedCrossRef Yeh WL, Lin SS, Yuan LJ, Lee KF, Lee MY, Ueng SW. Effects of hyperbaric oxygen treatment on tendon graft and tendon-bone integration in bone tunnel: biochemical and histological analysis in rabbits. J Orthop Res. 2007;25:636–45.PubMedCrossRef
44.
go back to reference Jukic I, Mišir M, Mihalj M, Mihaljevic Z, Sanela Unfirer S, Kibel D, et al. Mechanisms of HBO-induced vascular functional changes in diabetic animal models. In: Drenjančević I, editor., et al., Hyperbaric oxygen treatment in research and clinical practice—mechanisms of action in focus. London: IntechOpen; 2018. Jukic I, Mišir M, Mihalj M, Mihaljevic Z, Sanela Unfirer S, Kibel D, et al. Mechanisms of HBO-induced vascular functional changes in diabetic animal models. In: Drenjančević I, editor., et al., Hyperbaric oxygen treatment in research and clinical practice—mechanisms of action in focus. London: IntechOpen; 2018.
45.
go back to reference Godman CA, Chheda KP, Hightower LE, Perdrizet G, Shin DG, Giardina C. Hyperbaric oxygen induces a cytoprotective and angiogenic response in human microvascular endothelial cells. Cell Stress Chaperones. 2010;15:431–42.PubMedCrossRef Godman CA, Chheda KP, Hightower LE, Perdrizet G, Shin DG, Giardina C. Hyperbaric oxygen induces a cytoprotective and angiogenic response in human microvascular endothelial cells. Cell Stress Chaperones. 2010;15:431–42.PubMedCrossRef
Metadata
Title
Hyperbaric oxygen therapy efficacy on mandibular defect regeneration in rats with diabetes mellitus: an animal study
Authors
Rodina H. Eldisoky
Salwa A. Younes
Samia S. Omar
Hagar S. Gharib
Tarek A. Tamara
Publication date
01-12-2023
Publisher
BioMed Central
Keyword
Diabetes
Published in
BMC Oral Health / Issue 1/2023
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-023-02801-w

Other articles of this Issue 1/2023

BMC Oral Health 1/2023 Go to the issue