Recent advances in bone graft substitute for oral and maxillofacial applications: a review

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Review Paper 01/10/2019
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Recent advances in bone graft substitute for oral and maxillofacial applications: a review

N.M. Al-Namnam, Soher Nagi Jayash
Int. J. Biosci.15( 4), 70-94, October 2019.
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Bone grafts are generally used to promote new bone formation and guided tissue regeneration. It’s more commonly used in oral and maxillofacial reconstruction. To review and update of the biomedical application and clinical outcomes of most used bone graft substitutes in different procedures: sinus elevation, socket preservation and alveolar bone augmentation. A literature review was conducted using MEDLINE, MEDPILOT and SYSTEMATIC REVIEWS. It concentrated on manuscripts and overviews published in the last seventeen years (2000-2017). The key terms employed were names of natural and synthetics different recants bone graft scaffold substitutes, growths factors, stem cell and their combinations. The results of clinical studies and animal trials were emphasized. Clinical evidence of BMPs application and dosage remains limited and controversial results on osteconductivity of Ca-P bone substitute’s application are present.  The alveolar ride preservation and implant position after extraction depend on the attentive surgery procedure and the properties of using materials which capable to maintain the prior space and be helpful in implant support and bone tissue regeneration. Novel materials will likely to build up on innovative polymeric platforms with controlled biophysical and biological properties that enable the targeted delivery of growth factors and cells.


Al-Namnam NM, Kutty MG, Chai WL, Ha KO, Kim KH, Siar CH, Ngeow WC. 2017. An injectable poly (caprolactone trifumarate-gelatin microparticles)(PCLTF-GMPs) scaffold for irregular bone defects: Physical and mechanical characteristics. Materials Science and Engineering: C 72, 332-340.

Al-Namnam NM, Shanmuhasuntharam P, Ha KO, Ch Siar. 2010. Processed Allogeneic Dentine as a Scaffold for Bone Healing: An in Vivo, Australian Journal of Basic & Applied Sciences 4, 5932-5932-5940.

AlNamnam NMN, Kim KH, Chai WL, Ha KO, Siar CH, Ngeow WC. 2016. Modified poly (caprolactone trifumarate) with embedded gelatin microparticles as a functional scaffold for bone tissue engineering. Journal of Applied Polymer Science 133,

Araújo MG, Silva CO, Misawa M, Sukekava F. 2015. Alveolar socket healing: what can we learn? Periodontology 2000 68, 122-134.

Askarzadeh K, Orang F, Moztarzadeh F. 2005. Fabrication and characterization of a porous composite scaffold based on gelatin and hydroxyapatite for bone tissue engineering. Iranian Polymer Journal 14, 511-520.

Balaji S. 2011. Alveolar cleft defect closure with iliac bone graft, rhBMP-2 and rhBMP-2 with zygoma shavings: Comparative study. Annals of maxillofacial surgery 1, 8.

Baldini N, De Sanctis M, Ferrari M. 2011. Deproteinized bovine bone in periodontal and implant surgery. Dental materials 27, 61-70.

Bauer TW, Muschler GF. 2000. Bone graft materials: an overview of the basic science. Clinical orthopaedics and related research 371, 10-27.

Beaman FD, Bancroft LW, Peterson JJ, Kransdorf MJ, Menke DM, DeOrio JK. 2006. Imaging characteristics of bone graft materials. Radiographics 26, 373-388.

Block MS, Finger I, Lytle R. 2002. Human mineralized bone in extraction sites before implant placement: Preliminary results. The Journal of the American Dental Association 133, 1631-1638.

Brkovic B, Prasad HS, Konandreas G, Milan R, Antunovic D, Sándor G, Rohrer MD. 2008. Simple preservation of a maxillary extraction socket using beta-tricalcium phosphate with type I collagen: preliminary clinical and histomorphometric observations. J Can Dent Assoc 74, 523-528.

Burg KJ, Porter S, Kellam JF. 2000. Biomaterial developments for bone tissue engineering. Biomaterials 21, 2347-2359.

Calixto RFE, Teófilo JM, Brentegani LG, Lamano-Carvalho TL. 2007. Alveolar wound healing after implantation with a pool of commercially available bovine bone morphogenetic proteins (BMPs): a histometric study in rats. Brazilian dental journal 18, 29-33.

Cao L, Arany PR, Wang YS, Mooney DJ. 2009. Promoting angiogenesis via manipulation of VEGF responsiveness with notch signaling. Biomaterials 30, 4085-4093.

Chiappelli F. 2010. Future avenues of research synthesis for evidence-based clinical decision making. Pages 243-247. Evidence-Based Practice: toward Optimizing Clinical Outcomes,  Springer.

Contar CMM, Sarot JR, Bordini J, Galvão GH, Nicolau GV, Machado MAN. 2009. Maxillary ridge augmentation with fresh-frozen bone allografts. Journal of Oral and Maxillofacial Surgery 67, 1280-1285.

Contar CMM, Sarot JR, da Costa MB, Bordini Jr J, de Lima AAS, Alanis LRA, Trevilatto PC, Machado MÂN. 2011. Fresh-frozen bone allografts in maxillary ridge augmentation: histologic analysis. Journal of Oral Implantology 37, 223-231.

Cordaro L, Bosshardt DD, Palattella P, Rao W, Serino G, Chiapasco M. 2008. Maxillary sinus grafting with Bio‐Oss® or Straumann® Bone Ceramic: histomorphometric results from a randomized controlled multicenter clinical trial. Clinical oral implants research 19, 796-803.

Coutinho DF, Sant SV, Shin H, Oliveira JT, Gomes ME, Neves NM, Khademhosseini A, Reis RL. 2010. Modified Gellan Gum hydrogels with tunable physical and mechanical properties. Biomaterials 31, 7494-7502.

Damien E, Revell P. 2004. Coralline hydroxyapatite bone graft substitute: A review of experimental studies and biomedical applications. Journal of applied biomaterials & biomechanics: JABB 2, 65-73.

Darby I, Chen S, De Poi R. 2008. Ridge preservation: what is it and when should it be considered. Australian dental journal 53, 11-21.

Del Fabbro M, Testori T, Francetti L, Weinstein R. 2005. Systematic review of survival rates for implants placed in the grafted maxillary sinus. The Journal of Prosthetic Dentistry 94, 266.

Farina R, Trombelli L. 2011. Wound healing of extraction sockets. Endodontic Topics 25, 16-43.

Feng X, Li Z, Wei J, Feng Z, Wu W, Zhao Y. 2018. Injectable cartilaginous template transformed BMSCs into vascularized bone. Scientific Reports 8, 8244.

Feuille F, Knapp CI, Brunsvold MA, Mellonig JT. 2003. Clinical and histologic evaluation of bone-replacement grafts in the treatment of localized alveolar ridge defects. Part 1: Mineralized freeze-dried bone allograft. International Journal of Periodontics & Restorative Dentistry 23.

Fickl S, Zuhr O, Wachtel H, Stappert CF, Stein JM, Hürzeler MB. 2008. Dimensional changes of the alveolar ridge contour after different socket preservation techniques. Journal of clinical periodontology 35, 906-913.

Fiedler J, Röderer G, Günther KP, Brenner RE. 2002. BMP‐2, BMP‐4, and PDGF‐bb stimulate chemotactic migration of primary human mesenchymal progenitor cells. Journal of cellular biochemistry 87, 305-312.

Fischbach C, Mooney DJ. 2007. Polymers for pro-and anti-angiogenic therapy. Biomaterials 28, 2069-2076.

Fisher JP, Dean D, Mikos AG. 2002. Photocrosslinking characteristics and mechanical properties of diethyl fumarate/poly (propylene fumarate) biomaterials. Biomaterials 23, 4333-4343.

Friedmann A, Dard M, Kleber BM, Bernimoulin JP, Bosshardt DD. 2009. Ridge augmentation and maxillary sinus grafting with a biphasic calcium phosphate: histologic and histomorphometric observations. Clinical oral implants research 20, 708-714.

Froum SJ, Wallace SS, Cho SC, Elian N, Tarnow DP. 2008. Histomorphometric comparison of a biphasic bone ceramic to anorganic bovine bone for sinus augmentation: 6-to 8-month postsurgical assessment of vital bone formation. A pilot study. International Journal of Periodontics & Restorative Dentistry 28.

Garg V, Giraddi GB, Roy S. 2015. Comparison of efficacy of mandible and iliac bone as autogenous bone graft for orbital floor reconstruction. Journal of maxillofacial and oral surgery 14, 291-298.

Giannoudis PV, Dinopoulos H, Tsiridis E. 2005. Bone substitutes: an update. Injury 36: S20-S27.

Heberer S, Al-Chawaf B, Jablonski C, Nelson JJ, Lage H, Nelson K. 2011. Healing of ungrafted and grafted extraction sockets after 12 weeks: a prospective clinical study. International Journal of Oral & Maxillofacial Implants 26.

Hile DD, Sonis ST, Doherty SA, Tian XY, Zhang Q, Jee WS, Trantolo DJ. 2005. Dimensional stability of the alveolar ridge after implantation of a bioabsorbable bone graft substitute: a radiographic and histomorphometric study in rats. Journal of Oral Implantology 31, 68-76.

Horowitz RA, Mazor Z, Miller RJ, Krauser J, Prasad HS, Rohrer MD. 2009. Clinical evaluation alveolar ridge preservation with a beta-tricalcium phosphate socket graft. Compend Contin Educ Dent 30, 588-590.

Iasella JM, Greenwell H, Miller RL, Hill M, Drisko C, Bohra AA, Scheetz JP. 2003. Ridge preservation with freeze-dried bone allograft and a collagen membrane compared to extraction alone for implant site development: a clinical and histologic study in humans. Journal of periodontology 74, 990-999.

Jabbari E, Wang S, Lu L, Gruetzmacher JA, Ameenuddin S, Hefferan TE, Currier BL, Windebank AJ, Yaszemski MJ. 2005. Synthesis, material properties, and biocompatibility of a novel self-cross-linkable poly (caprolactone fumarate) as an injectable tissue engineering scaffold. Biomacromolecules 6, 2503-2511.

Kao RT, Murakami S, Beirne OR. 2009. The use of biologic mediators and tissue engineering in dentistry. Periodontology 2000 50, 127-153.

Kattimani VS, Chakravarthi PS, Kanumuru NR, Subbarao VV, Sidharthan A, Kumar TS, Prasad LK. 2014. Eggshell derived hydroxyapatite as bone graft substitute in the healing of maxillary cystic bone defects: a preliminary report. Journal of international oral health: JIOH 6, 15.

Kesmas S, Swasdison S, Yodsanga S, Sessirisombat S, Jansisyanont P. 2010. Esthetic alveolar ridge preservation with calcium phosphate and collagen membrane: preliminary report. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 110, e24-e36.

Kim HW, Lee SY, Bae CJ, Noh YJ, Kim HE, Kim HM, Ko JS. 2003. Porous ZrO 2 bone scaffold coated with hydroxyapatite with fluorapatite intermediate layer. Biomaterials 24, 3277-3284.

Kim SG, Jeong JH, Che X, Park YT, Lee SW, Jung ES, Choe S, Choi JY. 2013. Reconstruction of radial bone defect using gelatin sponge and a BMP-2 combination graft. BMB reports 46, 328.

Kim SY, Kim YK, Park YH, Park JC, Ku JK, Um IW, Kim JY. 2017. Evaluation of the Healing Potential of Demineralized Dentin Matrix Fixed with Recombinant Human Bone Morphogenetic Protein-2 in Bone Grafts. Materials (Basel) 10. E1049.

Kim YK, Yun PY, Lim SC, Kim SG, Lee HJ, Ong JL. 2008. Clinical evaluations of OSTEON® as a new alloplastic material in sinus bone grafting and its effect on bone healing. Journal of Biomedical Materials Research Part B: Applied Biomaterials 86, 270-277.

Knapp CI, Feuille F, Cochran DL, Mellonig JT. 2003. Clinical and histologic evaluation of bone-replacement grafts in the treatment of localized alveolar ridge defects. Part 2: bioactive glass particulate. International Journal of Periodontics & Restorative Dentistry 23.

Kubo T, Sugita T, Shimose S, Arihiro K, Tanaka H, Nobuto H, Tanaka K, Ochi M. 2004. Histological findings in a human autogenous pasteurized bone graft. Anticancer research 24, 1893-1896.

Kumar PG, Kumar JA, Anumala N, Reddy KP, Avula H, Hussain SN. 2011. Volumetric analysis of intrabony defects in aggressive periodontitis patients following use of a novel composite alloplast: A pilot study. Quintessence International 42, 375-84.

Leclerc E, Baudoin R, Corlu A, Griscom L, Duval JL, Legallais C. 2007. Selective control of liver and kidney cells migration during organotypic cocultures inside fibronectin-coated rectangular silicone microchannels. Biomaterials 28, 1820-1829.

Lee DW, Pi SH, Lee SK, Kim EC. 2009. Comparative histomorphometric analysis of extraction sockets healing implanted with bovine xenografts, irradiated cancellous allografts, and solvent-dehydrated allografts in humans. International Journal of Oral & Maxillofacial Implants 24, 609-15.

Lee K, Silva EA, Mooney DJ. 2011. Growth factor delivery-based tissue engineering: general approaches and a review of recent developments. Journal of the Royal Society Interface 8, 153-170.

Leor J, Amsalem Y, Cohen S. 2005. Cells, scaffolds, and molecules for myocardial tissue engineering. Pharmacology & therapeutics 105, 151-163.

Lorenz J, Al-Maawi S, Sader R, Ghanaati S. 2018. Individualized titanium mesh combined with platelet-rich fibrin and deproteinized bovine bone: A new approach for challenging augmentation. Joural Oral Implantol

Meeder PJ, Eggers C. 1994. 1. The history of autogenous bone grafting. Injury 25, SA2-SA4.

Meijer GJ, de Bruijn JD, Koole R, van Blitterswijk CA. 2007. Cell-based bone tissue engineering. PLoS medicine 4, e9.

Meinel L, Karageorgiou V, Fajardo R, Snyder B, Shinde-Patil V, Zichner L, Kaplan D, Langer R, Vunjak-Novakovic G. 2004. Bone tissue engineering using human mesenchymal stem cells: effects of scaffold material and medium flow. Annals of biomedical engineering 32, 112-122.

Middleton JC, Tipton AJ. 2000. Synthetic biodegradable polymers as orthopedic devices. Biomaterials 21: 2335-2346.

Neuss S, Denecke B, Gan L, Lin Q, Bovi M, Apel C, Wöltje M, Dhanasingh A, Salber J, Knüchel R. 2011. Transcriptome analysis of MSC and MSC-derived osteoblasts on Resomer® LT706 and PCL: impact of biomaterial substrate on osteogenic differentiation. PloS one 6, e23195.

Nkenke E, RadespielTröger M, Wiltfang J, SchultzeMosgau S, Winkler G, Neukam FW. 2002. Morbidity of harvesting of retromolar bone grafts: a prospective study. Clinical oral implants research 13, 514-521.

Owczarek B, Kiernicka M, Gałkowska E, Wysokińska-Miszczuk J. 2003. The application of Bio-Oss and Bio-Gide as implant materials in the complex treatment of aggressive periodontitis. Pages 392-396. Annales Universitatis Mariae Curie-Sklodowska. Sectio D: Medicina.

Park M, Mah YJ, Kim DH, Kim ES, Park EJ. 2015. Demineralized deciduous tooth as a source of bone graft material: its biological and physicochemical characteristics. Oral surgery, oral medicine, oral pathology and oral radiology 120, 307-314.

Peter SJ, Lu L, Kim DJ, Mikos AG. 2000. Marrow stromal osteoblast function on a poly (propylene fumarate)/β-tricalcium phosphate biodegradable orthopaedic composite. Biomaterials 21, 1207-1213.

Porter JR, Ruckh TT, Popat KC. 2009. Bone tissue engineering: a review in bone biomimetics and drug delivery strategies. Biotechnology progress 25: 1539-1560.

Rani VD, Vinoth-Kumar L, Anitha V, Manzoor K, Deepthy M, Shantikumar VN. 2012. Osteointegration of titanium implant is sensitive to specific nanostructure morphology. Acta biomaterialia 8, 1976-1989.

Rodella LF, Favero G, Labanca M. 2011. Biomaterials in maxillofacial surgery: membranes and grafts. International journal of biomedical science: IJBS 7, 81.

Sabhlok S, Waknis PP, Gadre KS. 2014. Applications of coronoid process as a bone graft in maxillofacial surgery. Journal of Craniofacial Surgery 25: 577-580.

Salgado CL, Sanchez EM, Zavaglia CA, Granja PL. 2012a. Biocompatibility and biodegradation of polycaprolactone‐sebacic acid blended gels. Journal of Biomedical Materials Research Part A 100, 243-251.

Salgado CL, Sanchez E, Zavaglia CA, GranjaPL.2012b. Biocompatibility and biodegradation of polycaprolactone‐sebacic acid blended gels. Journal of Biomedical Materials Research Part A 100, 243-251.

Sartori S, Silvestri M, Forni F, Icaro Cornaglia A, Tesei P, Cattaneo V. 2003. Ten‐year follow‐up in a maxillary sinus augmentation using anorganic bovine bone (Bio‐Oss). A case report with histomorphometric evaluation. Clinical oral implants research 14, 369-372.

Schlee M, Esposito M. 2009. Aesthetic and patient preference using a bone substitute to preserve extraction sockets under pontics. A cross-sectional survey. Eur J Oral Implantol 2, 209-217.

Schlegel KA, Zimmermann R, Thorwarth M, Neukam FW, Klongnoi B, Nkenke E, Felszeghy E. 2007. Sinus floor elevation using autogenous bone or bone substitute combined with platelet-rich plasma. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 104: e15-e25.

Schmidlin P, Nicholls F, Kruse A, Zwahlen R, Weber F. 2013. Evaluation of moldable, in situ hardening calcium phosphate bone graft substitutes. Clinical oral implants research 24, 149-157.

Schwartz Z, Goldstein M, Raviv E, Hirsch A, Ranly DM, Boyan BD. 2007. Clinical evaluation of demineralized bone allograft in a hyaluronic acid carrier for sinus lift augmentation in humans: a computed tomography and histomorphometric study. Clinical oral implants research 18, 204-211.

Seong JM, Kim BC, Park JH, Kwon IK, Mantalaris A, Hwang YS. 2010. Stem cells in bone tissue engineering. Biomedical Materials 5, 062001.

Shastri VP, Padera RF, Tarcha P, Langer R. 2004. A preliminary report on the biocompatibility of photopolymerizable semi-interpenetrating anhydride networks. Biomaterials 25, 715-721.

Shin H, Jo S, Mikos AG. 2003. Biomimetic materials for tissue engineering. Biomaterials 24,  4353-4364.

Simpson D, Kakarala G, Hampson K, Steele N, Ashton B. 2007. Viable cells survive in fresh frozen human bone allografts. Acta Orthopaedica 78, 26-30.

Stavropoulos A, Kostopoulos L, Mardas N, Randel Nyengaard J, Karring T. 2001. Deproteinized bovine bone used as an adjunct to guided bone augmentation: an experimental study in the rat. Clinical implant dentistry and related research 3, 156-165.

Temenoff JS, Mikos AG. 2000. Injectable biodegradable materials for orthopedic tissue engineering. Biomaterials 21, 2405-2412.

Thakur G, Rousseau D, Rafanan RR. 2013. Gelatin based matrices for drug delivery applications.

Thompson DM, Rohrer MD, Prasad HS. 2006. Comparison of bone grafting materials in human extraction sockets: clinical, histologic, and histomorphometric evaluations. Implant dentistry 15, 89-96.

Thuaksuban N, Nuntanaranont T, Pripatnanont P. 2010. A comparison of autogenous bone graft combined with deproteinized bovine bone and autogenous bone graft alone for treatment of alveolar cleft. International journal of oral and maxillofacial surgery 39, 1175-1180.

van Hout WM, van der Molen ABM, Breugem CC, Koole R, Van Cann EM. 2011. Reconstruction of the alveolar cleft: can growth factor-aided tissue engineering replace autologous bone grafting? A literature review and systematic review of results obtained with bone morphogenetic protein-2. Clinical Oral Investigations 15, 297-303.

Wang S, Yaszemski MJ, Knight AM, Gruetzmacher JA, Windebank AJ, Lu L. 2009. Photo-crosslinked poly (ε-caprolactone fumarate) networks for guided peripheral nerve regeneration: Material properties and preliminary biological evaluations. Acta biomaterialia 5, 1531-1542.

Wasielewski RC, Sheridan KC, Lubbers MA. 2008. Coralline hydroxyapatite in complex acetabular reconstruction. Orthopedics 31, 367.

Wattanutchariya W, Changkowchai W. 2014. Characterization of porous scaffold from chitosan-gelatin/hydroxyapatite for bone grafting. Pages 12-14. Proceedings of the International MultiConference of Engineers and Computer Scientists.

Yamada Y, Ueda M, Naiki T, Takahashi M, Hata K-I, Nagasaka T. 2004. Autogenous injectable bone for regeneration with mesenchymal stem cells and platelet-rich plasma: tissue-engineered bone regeneration. Tissue engineering 10, 955-964.

Yamada Y, Nakamura S, Ito K, Umemura E, Hara K, Nagasaka T, Abe A, Baba S, Furuichi Y, Izumi Y. 2013. Injectable bone tissue engineering using expanded mesenchymal stem cells. Stem Cells 31, 572-580.

Yamauchi K, Takahashi T, Funaki K, Hamada Y, Yamashita Y. 2010. Histological and histomorphometrical comparative study of β-tricalcium phosphate block grafts and periosteal expansion osteogenesis for alveolar bone augmentation. International journal of oral and maxillofacial surgery 39, 1000-1006.

Yates DM, Brockhoff HC, Finn R, Phillips C. 2013. Comparison of intraoral harvest sites for corticocancellous bone grafts. Journal of Oral and Maxillofacial Surgery 71, 497-504.

Zagris N. 2001. Extracellular matrix in development of the early embryo. Micron 32, 427-438.

Zecha P, Schortinghuis J, Van der Wal J, Nagursky H, Van Den Broek K, Sauerbier S, Vissink A, Raghoebar G. 2011. Applicability of equine hydroxyapatite collagen (eHAC) bone blocks for lateral augmentation of the alveolar crest. A histological and histomorphometric analysis in rats. International journal of oral and maxillofacial surgery 40, 533-542.

Zipfel GJ, Guiot BH, Fessler RG. 2003. Bone grafting. Neurosurgical focus 14, 1-8.