Bone Engineering Arash Khojasteh, DMD, OMFS Assistant Professor of Oral and Maxillofacial Surgery Shahid Beheshti University of Medical Sciences

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1 Bone Engineering Arash Khojasteh, DMD, OMFS Assistant Professor of Oral and Maxillofacial Surgery Shahid Beheshti University of Medical Sciences

2 Tissue Engineering VS Regenerative Medicine Insitu Vs Invitro Osteogenesis

3 Strategy for Engineered Bone Cells (Osteoblast or Osteoprogenitor) Scaffold ( synthetic or natural) Growth Factor

4 Dentomaxillofacial Regeneration In situ Osteogenesis Protected Healing Space Inductive agent Transfer In situ Osteogenesis Scaffold

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11 Growth factor Therapy Cell therapy

12 Maxillary Sinus Augmentation Boyne PJ, Marx RE, Nevins M et al; Int J Periodontics Restorative Dent. 1997;17:11-25

13 Boyne PJ, Marx RE, Nevins M et al; Int J Periodontics Restorative Dent. 1997;17:11-25

14 Boyne PJ, Marx RE, Nevins M et al; Int J Periodontics Restorative Dent. 1997;17:11-25

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16 Herford and PJ Boyne

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19 Alan S. Herford. Philip J. Boyne. Rick Rawson. Roland P. Williams J Oral Maxillofac Surg 65: , 2007

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23 RhBMP-2 Animal Critical Size defect Study ( Wikesjo) Human studies

24 Animal Critical Size defect Study RhBMP-2 and ACS Clinical Oral Impl Res 1997;

25 Clinical Oral Impl Res 1997;

26 Protected Bone Healing with DFDBA JOMI 1997; 12:

27 Protected Bone Healing with DFDBA JOMI 1997; 12:

28 Protected Healing Space Vs Inductive transfer Clinic Oral Impl Res 2004; ; 15:

29 Protected Healing Space Vs Indcutive transfer Clinic Oral Impl Res 2004; ; 15:

30 Protected Healing Space Vs Indcutive transfer Clinic Oral Impl Res 2004; ; 15:

31 Protected Healing Space Vs Inductive agent transfer Clinic Oral Impl Res 2004; 15:

32 Simion et al. 2009

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38 Susin et al: J Clin Periodontol 2010; 37:

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41 Cell therapy Differentiated cell Therapy Mesenchymal Stem Cell Therapy Bone marrow aspirate therapy

42 Differentiated cell Therapy Spontaneous tooth eruption after alveolar cleft osteoplasty using tissue-engineered bone: a case report Oral Surg Oral Med OralPathol Oral Radiol Endod 2008;105:440-4)

43 Mesenchymal Stem Cell Therapy Animal Studies Human Studies

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46 Culture

47 Alizarin Red Staining

48 RT-PCR

49 In vitro H&E Staining of Scaffold

50 Scaffold Selection Accelerated bone regeneration

51 SEM Analysis. HA/TCP

52 SEM Analysis: BioOss

53 Ectopic Bone Formation Investigation Application of mesenchymal stem cells in dog masseter muscle

54 HA/TCP

55 BioOss

56 Ectopic Bone formation in Masseter Muscle Bone Ratio (%) HA/TCP BioOss

57 MSCs induced bone formation in Bony defects Application of MSCs in 10 mm through and Through Defects in dog mandible

58 Marrow-derived mesenchymal stem cells-directed bone regeneration in the dog mandible: A comparison between biphasic calcium phosphate and natural bone mineral Jafarian M, Eslaminejad MB, Khojasteh A, Mashhadi Abbas F, Dehghan MM, Hassanizadeh R, Houshmand B. Oral Surg Oral Med Oral Pathol Oral Radiol Endod May;105(5):e14-24.

59 Scanning electron microscopy analysis HA/TCP HA/TCP

60 Scanning electron microscopy analysis

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62 Dr Jafarian, Dr Khojasteh, Dr Hassanzadeh

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66 Mesenchymal stem cells enhance bone regeneration in rat calvarial critical size defects more than platelete-rich plasma Arash Khojasteh, Mohammad reza Baghban Eslaminejad, Hamid Nazarian, Oral Surg Oral Med Oral Pathol Oral Radiol Endod Sep;106(3):356-62;

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68 MSCs more than PRP

69 Sinus augmentation using human mesenchymal stem cells loaded into a beta tricalcium phosphate/hydroxyapatite scaffold Shayesteh YS, Khojasteh A, Soleimani M, Alikhasi M, Khoshzaban A, Ahmadbeigi N Oral Surg Oral Med Oral Pathol Oral Radiol Endod Aug;106(2): Epub 2008 Apr 18.

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76 Secondary repair of alveolar clefts using human mesenchymal stem cells Hossein Behnia, Arash Khojasteh, Masoud Soleimani, Azita Tehranchi, Ahad Khoshzaban, Saeed Hidari Keshel, Reza Atashi, PhD Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009,Aug;106(2): Epub 2008 Apr 18.

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79 25%-34% Bone fill

80 Triad of Tissue Engineering JCMF, 2011

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84 Gender Defect Type Age at surgery (Y.O) 3 months postoperative bone volume (%) F Right PMC F Right PMC Left PMC 48.3 M Right PMC (Mean) 51.3 (Mean)

85 J.Oral Implantology 2011

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88 Group 1(Test) Group2 P Value (control) VBL (mm) P<0.05 BF(8 weeks)% 28.5± %±1.8 P<0.05

89 Insitu Osteognesis Autogenous bone is the gold standard

90 Nano scaffolds Nanosilica HA

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99 GEM 21s

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106 ㅢ ML253

107 ID: ML253 Image analysis(cross-section) ~2(Top) 3~4(Middle) 5~6(Bottom)

108 ID: ML253 Region of Interest Top Select area Top Bottom Middle Threshold; New bone area About : 5.6% Bottom Threshold; Total bone area(newbone+bonegraft) About : 27.4% => Bone volume ratio depends on the area(roi). Cross-section image

109 3D axis Image

110 Cells (Osteoblast or Osteoprogenitor) Scaffold ( synthetic or natural) Growth Factor

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115 Strategy for Engineered Bone Scaffold Cells Biodynamic Bioreactor Pharmaceutics Clinical Application

116 Scaffold Key issues Stimulate cell function: bioactive factors on material surface, drug/gene in material compliance/degradation matching

117 Biodynamic Bioreactor Deliver nutrients and oxygen to maintain cell viability throughout scaffold media in scaffold Perfusion System Goldstein et al Biomaterials 22:1279, 2001

118 In situ Osteogenesis Protected Healing Space Inductive agent Transfer In situ Osteogenesis Scaffold

119 Protected Healing Space

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124 Biphasic Synthetic Material As an occlusive resorptive membrane

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142 Dr Jafarian, Dr Khojasteh, Dr Hassanzadeh

143 Thank you for your Consideration