Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo micro-computed tomographic and histologic experiment in rats

Abstract

The use of stem cells to accelerate bone regeneration has been monitored in real time in rats using three-dimensional imaging. The work was carried out by Khalid Al-Hezaimi and colleagues at King Saud University, Saudi Arabia, in collaboration with No-Hee Park of the University of California. Mesenchymal stem cells were harvested from rat hind leg bones. The researchers then drilled holes in rat skulls and filled them with stem cells covered with collagen membrane with and without tricalcium phosphate granules, or collagen membrane alone. Micro-computed tomography revealed that differentiation of stem cells into mature bone cells took approximately 2 weeks. Bone regeneration over a 10-week period was significantly faster with the stem cell treatments. Adding tricalcium phosphate weakened the regenerated bone, despite previous work suggesting it might promote bone cell formation

Keywords

bone marrow-derived mesenchymal stem / collagen membrane / critical size defect / guided bone regeneration / tricalcium phosphate

References

[1] Mellonig JT, Valderrama Mdel P, Cochran DL. Histological and clinical evaluation of recombinant human platelet-derived growth factor combined with beta tricalcium phosphate for the treatment of human class III furcation defects. Int J Periodontics Restorative Dent, 2009, 29(2): 169-177.

[2] Urban IA, Jovanovic SA, Lozada JL. Vertical ridge augmentation using guided bone regeneration (GBR) in three clinical scenarios prior to implant placement: a retrospective study of 35 patients 12 to 72 months after loading. Int J Oral Maxillofac Implants, 2009, 24(3): 502-510.

[3] Proussaefs P, Lozada J. The use of resorbable collagen membrane in conjunction with autogenous bone graft and inorganic bovine mineral for buccal/labial alveolar ridge augmentation: a pilot study. J Prosthet Dent, 2003, 90(6): 530-538.

[4] Hämmerle CH, Jung RE, Yaman D. Ridge augmentation by applying bioresorbable membranes and deproteinized bovine bone mineral: a report of twelve consecutive cases. Clin Oral Implants Res, 2008, 19(1): 19-25.

[5] Hämmerle CH, Lang NP. Single stage surgery combining transmucosal implant placement with guided bone regeneration and bioresorbable materials. Clin Oral Implants Res, 2001, 12(1): 9-18.

[6] Nevins M, Nevins ML, Schupbach P. A prospective, randomized controlled preclinical trial to evaluate different formulations of biphasic calcium phosphate in combination with a hydroxyapatite collagen membrane to reconstruct deficient alveolar ridges. J Oral Implantol, 2013, 39(2): 133-139.

[7] Saffar JL, Colombier ML, Detienville R. Bone formation in tricalcium phosphate-filled periodontal intrabony lesions. Histological observations in humans. J Periodontol, 1990, 61(4): 209-216.

[8] Stahl SS, Froum S. Histological evaluation of human intraosseous healing responses to the placement of tricalcium phosphate ceramic implants. I. Three to eight months. J Periodontol, 1986, 57(4): 211-217.

[9] Bowers GM, Vargo JW, Levy B. Histologic observations following the placement of tricalcium phosphate implants in human intrabony defects. J Periodontol, 1986, 57(5): 286-287.

[10] Schenk RK, Buser D, Hardwick WR. Healing pattern of bone regeneration in membrane-protected defects: a histologic study in the canine mandible. Int J Oral Maxillofac Implants, 1994, 9(1): 13-29.

[11] Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet, 1970, 3(4): 393-403.

[12] Gimbel M, Ashley RK, Sisodia M. Repair of alveolar cleft defects: reduced morbidity with bone marrow stem cells in a resorbable matrix. J Craniofac Surg, 2007, 18(4): 895-901.

[13] Zigdon-Giladi H, Bick T, Lewinson D. Co-transplantation of endothelial progenitor cells and mesenchymal stem cells promote neovascularization and bone regeneration. Clin Implant Dent Relat Res, 2015, 17(2): 353-359.

[14] Zigdon-Giladi H, Lewinson D, Bick T. Mesenchymal stem cells combined with barrier domes enhance vertical bone formation. J Clin Periodontol, 2013, 40(2): 196-202.

[15] Camelo M, Nevins ML, Schenk RK. Clinical, radiographic, and histologic evaluation of human periodontal defects treated with Bio-Oss and Bio-Gide. Int J Periodontics Restorative Dent, 1998, 18(4): 321-331.

[16] Nevins ML, Camelo M, Lynch SE. Evaluation of periodontal regeneration following grafting intrabony defects with bio-oss collagen: a human histologic report. Int J Periodontics Restorative Dent, 2003, 23(1): 9-17.

[17] Nevins M, Nevins ML, Karimbux N. The combination of purified recombinant human platelet-derived growth factor-BB and equine particulate bone graft for periodontal regeneration. J Periodontol, 2012, 83(5): 565-573.

[18] Al-Hezaimi K, Iezzi G, Rudek I. Histomorphometric analysis of bone regeneration using a dual layer of membranes (dPTFE placed over collagen) in fresh extraction sites: a canine model. J Oral Implantol, 2015, 41(2): 188-195.

[19] Al-Hazmi BA, Al-Hamdan KS, Al-Rasheed A. Efficacy of using PDGF and xenograft with or without collagen membrane for bone regeneration around immediate implants with induced dehiscence-type defects: a microcomputed tomographic study in dogs. J Periodontol, 2013, 84(3): 371-378.

[20] Al-Hezaimi K, Al-Shabeeb MS, Al-Askar M. Microcomputed tomographic analysis of the alveolar ridge alteration around extraction sites with and without immediate implants placement: in vivo study. Clin Implant Dent Relat Res, 2014, 16(2): 223-229.

[21] Al-Askar M, O’Neill R, Stark PC. Effect of single and contiguous teeth extractions on alveolar bone remodeling: a study in dogs. Clin Implant Dent Relat Res, 2013, 15(4): 569-575.

[22] Fischer AH, Jacobson KA, Rose J. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc, 2008, 2008: pdb.prot4986.

[23] Schmid J, Wallkamm B, Hämmerle CH. The significance of angiogenesis in guided bone regeneration. A case report of a rabbit experiment. Clin Oral Implants Res, 1997, 8(3): 244-248.

[24] Dodde R 2nd, Yavuzer R, Bier UC. Spontaneous bone healing in the rabbit. J Craniofac Surg, 2000, 11(4): 346-349.

[25] Kanczler JM, Oreffo RO. Osteogenesis and angiogenesis: the potential for engineering bone. Eur Cell Mater, 2008, 15: 100-114.

[26] Zigdon-Giladi H, Bick T, Lewinson D. Mesenchymal stem cells and endothelial progenitor cells stimulate bone regeneration and mineral density. J Periodontol, 2014, 85(7): 984-990.

[27] Zachos T, Diggs A, Weisbrode S. Mesenchymal stem cell-mediated gene delivery of bone morphogenetic protein-2 in an articular fracture model. Mol Ther, 2007, 15(8): 1543-1550.

[28] Birmingham E, Niebur GL, McHugh PE. Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. Eur Cell Mater, 2012, 23: 13-27.

[29] Hoemann CD, El-Gabalawy H, McKee MD. In vitro osteogenesis assays: influence of the primary cell source on alkaline phosphatase activity and mineralization. Pathol Biol, 2009, 57(4): 318-323.

[30] Aubin JE. Regulation of osteoblast formation and function. Rev Endocr Metab Disord, 2001, 2(1): 81-94.

[31] Burra S, Nicolella DP, Francis WL. Dendritic processes of osteocytes are mechanotransducers that induce the opening of hemichannels. Proc Natl Acad Sci U S A, 2010, 107(31): 13648-13653.

[32] You L, Temiyasathit S, Lee P. Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading. Bone, 2008, 42(1): 172-179.

[33] Birnbaum RS, Bowsher RR, Wiren KM. Changes in IGF-I and -II expression and secretion during the proliferation and differentiation of normal rat osteoblasts. J Endocrinol, 1995, 144(2): 251-259.

[34] Srivastava AK, Libanati C, Oberrauch W. Analytical and clinical evaluation of the Bio-Rad HPLC kit for measurement of type I collagen cross links. J Bone Miner Metab, 2003, 21(3): 134-144.

[35] Khoshzaban A, Mehrzad S, Tavakoli V. The comparative effectiveness of demineralized bone matrix, beta-tricalcium phosphate, and bovine-derived anorganic bone matrix on inflammation and bone formation using a paired calvarial defect model in rats. Clin Cosmet Investig Dent, 2011, 3: 69-78.