Carrier systems for bone morphogenetic proteins: An overview of biomaterials used for dentoalveolar and maxillofacial bone regeneration

Japanese Dental Science Review - Tập 58 - Trang 316-327 - 2022
Alain Arias-Betancur1, Nicolás Badilla-Wenzel2, Álvaro Astete-Sanhueza2, Nicole Farfán-Beltrán1,3, Fernando José Dias4
1Department of Integral Adult Dentistry, Research Centre for Dental Sciences (CICO-UFRO), Dental School-Facultad de Odontología, Universidad de La Frontera, Temuco 4811230, Chile
2Dental School-Facultad de Odontología, Universidad de La Frontera, Temuco 4811230, Chile
3Universidad Adventista de Chile, Chillán 3780000, Chile
4Department of Integral Adult Dentistry, Oral Biology Research Centre (CIBO-UFRO), Dental School-Facultad de Odontología, Universidad de La Frontera, Temuco 4811230, Chile

Tài liệu tham khảo

Jimi, 2012, The current and future therapies of bone regeneration to repair bone defects, Int J Dent, 10.1155/2012/148261 Tan, 2016, Retention of teeth and oral health-related quality of life, J Dent Res, 95, 1350, 10.1177/0022034516657992 Dhingra, 2012, Oral rehabilitation considerations for partially edentulous periodontal patients, J Prosthodont, 21, 494, 10.1111/j.1532-849X.2012.00864.x Buser, 2017, Modern implant dentistry based on osseointegration: 50 years of progress, current trends and open questions, Periodontology 2000, 73, 7, 10.1111/prd.12185 Elgali, 2017, Guided bone regeneration: materials and biological mechanisms revisited, Eur J Oral Sci, 125, 315, 10.1111/eos.12364 Rogers, 2012, Autogenous bone graft: basic science and clinical implications, J Craniofacial Surg, 23, 323, 10.1097/SCS.0b013e318241dcba Titsinides, 2019, Bone grafting materials in dentoalveolar reconstruction: a comprehensive review, Jpn Dent Sci Rev, 55, 26, 10.1016/j.jdsr.2018.09.003 Retzepi, 2010, Guided bone regeneration: biological principle and therapeutic applications, Clin Oral Implants Res, 21, 567, 10.1111/j.1600-0501.2010.01922.x Stevenson, 1999, Biology of bone grafts, Orthop Clin N Am, 30, 543, 10.1016/S0030-5898(05)70107-3 Shibuya, 2015, Bone graft substitute: allograft and xenograft, Clin Podiatr Med Surg, 32, 21, 10.1016/j.cpm.2014.09.011 Kelly, 2016, Systematic review and meta-analysis of recombinant human bone morphogenetic protein-2 in localized alveolar ridge and maxillary sinus augmentation, J Oral Maxillofac Surg, 74, 928, 10.1016/j.joms.2015.11.027 Kowalczewski, 2018, Biomaterials for the delivery of growth factors and other therapeutic agents in tissue engineering approaches to bone regeneration, Front Pharmacol, 9, 513, 10.3389/fphar.2018.00513 Poniatowski, 2015, Transforming growth factor beta family: Insight into the role of growth factors in regulation of fracture healing biology and potential clinical applications, Mediat Inflamm, 10.1155/2015/137823 Ma, 2014, Biomimetic self-assembly of apatite hybrid materials: from a single molecular template to bi-/multi-molecular templates, Biotechnol Adv, 32, 744, 10.1016/j.biotechadv.2013.10.014 Qiu, 2020, Mesoporous hydroxyapatite nanoparticles mediate the release and bioactivity of BMP-2 for enhanced bone regeneration, ACS Biomater Sci Eng, 6, 2323, 10.1021/acsbiomaterials.9b01954 Scheufler, 1999, Crystal structure of human bone morphogenetic protein-2 at 2.7 A resolution, J Mol Biol, 287, 103, 10.1006/jmbi.1999.2590 Lo, 2012, Studies of bone morphogenetic protein-based surgical repair, Adv Drug Deliv Rev, 64, 1277, 10.1016/j.addr.2012.03.014 Miyazono, 2010, Bone morphogenetic protein receptors and signal transduction, J Biochem, 147, 35, 10.1093/jb/mvp148 Ducheyne, 2012, Biomaterials in the repair of sports injuries, Nat Mater, 11, 652, 10.1038/nmat3392 Luginbuehl, 2004, Localized delivery of growth factors for bone repair, Eur J Pharm Biopharm, 58, 197, 10.1016/j.ejpb.2004.03.004 Lauritano, 2020, Nanomaterials for periodontal tissue engineering: chitosan-based scaffolds, A Syst Rev Nanomater, 10, 605, 10.3390/nano10040605 Katagiri, 2015, Bone morphogenetic protein-induced heterotopic bone formation: what have we learned from the history of a half century?, Jpn Dent Sci Rev, 51, 42, 10.1016/j.jdsr.2014.09.004 Urist, 1979, Bone: formation by autoinduction, Science, 1965, 893 Carreira, 2014, Bone morphogenetic proteins: structure, biological function and therapeutic applications, Arch Biochem Biophys, 561, 64, 10.1016/j.abb.2014.07.011 el Bialy, 2017, Formulation, delivery and stability of bone morphogenetic proteins for effective bone regeneration, Pharm Res, 34, 1152, 10.1007/s11095-017-2147-x Derner, 2005, The bone morphogenic protein, Clin Podiatr Med Surg, 22, 607, 10.1016/j.cpm.2005.07.005 Axelrad, 2009, Bone morphogenetic proteins in orthopaedic surgery, Cytokine Growth Factor Rev, 20, 481, 10.1016/j.cytogfr.2009.10.003 Tsuji, 2006, BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing, Nat Genet, 38, 1424, 10.1038/ng1916 Riley, 1996, Bone morphogenetic protein-2: biology and applications, Clin Orthop Relat Res, 324, 39, 10.1097/00003086-199603000-00006 Daluiski, 2001, Bone morphogenetic protein-3 is a negative regulator of bone density, Nat Genet, 27, 84, 10.1038/83810 Aoki, 2001, Synergistic effects of different bone morphogeneticprotein type I receptors on alkaline phosphataseinduction, J Cell Sci, 114, 1483, 10.1242/jcs.114.8.1483 Ming Leong, 1996, Bone morphogenetic protein-4, Int J Biochem Cell Biol, 28, 1293, 10.1016/S1357-2725(96)00075-1 Wutzl, 2006, Bone morphogenetic proteins 5 and 6 stimulate osteoclast generation, J Biomed Mater Res A, 77, 75, 10.1002/jbm.a.30615 Ebisawa, 1999, Characterization of bone morphogenetic protein-6 signaling pathways inosteoblast differentiation, J Cell Sci, 112, 3519, 10.1242/jcs.112.20.3519 Boon, 2011, Bone morphogenetic protein 7: a broad-spectrum growth factor with multiple target therapeutic potency, Cytokine Growth Factor Rev, 22, 221, 10.1016/j.cytogfr.2011.08.001 Aluganti Narasimhulu, 2020, The role of bone morphogenetic protein 7 (BMP-7) in inflammation in heart diseases, Cells, 9, 280, 10.3390/cells9020280 Ozkaynak, 1992, Osteogenic protein-2. A new member of the transforming growth factor-β superfamily expressed early in embryogenesis, J Biol Chem, 267, 25220, 10.1016/S0021-9258(19)74028-9 Kósa, 2011, The protective role of bone morphogenetic protein-8 in the glucocorticoid-induced apoptosis on bone cells, Bone, 48, 1052, 10.1016/j.bone.2011.01.017 Cho, 2002, Differential temporal expression of members of the transforming growth factor superfamily during murine fracture healing, J Bone Miner Res, 17, 513, 10.1359/jbmr.2002.17.3.513 Sharff, 2009, Hey1 basic helix-loop-helix protein plays an important role in mediating BMP9-induced osteogenic differentiation of mesenchymal progenitor cells, J Biol Chem, 284, 649, 10.1074/jbc.M806389200 Brown, 2005, Crystal structure of BMP-9 and functional interactions with pro-region and receptors, J Biol Chem, 280, 25111, 10.1074/jbc.M503328200 Neuhaus, 1999, Heart specific expression of mouse BMP-10 a novel member of the TGF-b superfamily, Mech Dev, 80, 181, 10.1016/S0925-4773(98)00221-4 Chen, 2004, Bone morphogenetic proteins, Growth Factors, 22, 233, 10.1080/08977190412331279890 Li, 2011, Transgenic overexpression of bone morphogenetic protein 11 propeptide in skeleton enhances bone formation, Biochem Biophys Res Commun, 416, 289, 10.1016/j.bbrc.2011.11.019 Wikesjö, 2004, Periodontal repair in dogs: effect of recombinant human bone morphogenetic protein-12 (rhBMP-12) on regeneration of alveolar bone and periodontal attachment: a pilot study, J Clin Periodontol, 31, 662, 10.1111/j.1600-051X.2004.00541.x Shen, 2009, BMP-13 emerges as a potential inhibitor of bone formation, Int J Biol Sci, 5, 192, 10.7150/ijbs.5.192 Chhabra, 2005, BMP-14 deficiency inhibits long bone fracture healing a biochemical, histologic, and radiographic assessment, J Orthop Trauma, 19, 629, 10.1097/01.bot.0000177108.38461.9c Otsuka, 2000, Bone morphogenetic protein-15: Identification of target cells and biological functions, J Biol Chem, 275, 39523, 10.1074/jbc.M007428200 Sharapova, 2010, Production of the recombinant human bone morphogenetic protein-2 in Escherichia coli and testing of its biological activity in vitro and in vivo, Mol Biol, 44, 923, 10.1134/S0026893310060099 Gautschi, 2007, Bone morphogenetic proteins in clinical applications, ANZ J Surg, 77, 626, 10.1111/j.1445-2197.2007.04175.x U.S. Food and Drug Administration, FDA Approves Infuse Bone Graft for Sinus Augmentation and Localized Alveolar Ridge Augmentations, Press Release, 2007. Sreekumar, 2017, BMP9 a possible alternative drug for the recently withdrawn BMP7? New perspectives for (re-)implementation by personalized medicine, Arch Toxicol, 91, 1353, 10.1007/s00204-016-1796-6 Dickinson, 2008, Reduced morbidity and improved healing with bone morphogenic protein-2 in older patients with alveolar cleft defects, Plast Reconstr Surg, 121, 209, 10.1097/01.prs.0000293870.64781.12 Alonso, 2010, Evaluation of maxillary alveolar reconstruction using a resorbable collagen sponge with recombinant human bone morphogenetic protein-2 in cleft lip and palate patients, Tissue Eng Part C Methods, 16, 1183, 10.1089/ten.tec.2009.0824 Herford, 2007, Bone morphogenetic protein-induced repair of the premaxillary cleft, J Oral Maxillofac Surg, 65, 2136, 10.1016/j.joms.2007.06.670 Ramly, 2019, Safety and efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) in craniofacial surgery, Plast Reconstr Surg Glob Open, 7, 10.1097/GOX.0000000000002347 Woo, 2012, Adverse events reported after the use of recombinant human bone morphogenetic protein 2, J Oral Maxillofac Surg, 70, 765, 10.1016/j.joms.2011.09.008 Owens, 2011, Perioperative complications with rhBMP-2 in transforaminal lumbar interbody fusion, Eur Spine J, 20, 612, 10.1007/s00586-010-1494-7 Seeherman, 2005, Delivery of bone morphogenetic proteins for orthopedic tissue regeneration, Cytokine Growth Factor Rev, 16, 329, 10.1016/j.cytogfr.2005.05.001 Li, 2001, Delivering on the promise of bone morphogenetic proteins, Trends Biotechnol, 19, 255, 10.1016/S0167-7799(01)01665-1 Rodríguez-Vázquez, 2015, Chitosan and its potential use as a scaffold for tissue engineering in regenerative medicine, Biomed Res Int, 10.1155/2015/821279 Loh, 2013, Three-dimensional scaffolds for tissue engineering applications: role of porosity and pore size, Tissue Eng Part B Rev, 19, 485, 10.1089/ten.teb.2012.0437 Saito, 2005, Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins, Adv Drug Deliv Rev, 57, 1037, 10.1016/j.addr.2004.12.016 Shimauchi, 2013, Possible functional scaffolds for periodontal regeneration, Jpn Dent Sci Rev, 49, 118, 10.1016/j.jdsr.2013.05.001 Friess, 1998, Collagen - biomaterial for drug delivery, Eur J Pharm Biopharm, 45, 113, 10.1016/S0939-6411(98)00017-4 Xu, 2021, Collagen- and hyaluronic acid-based hydrogels and their biomedical applications, Mater Sci Eng R Rep, 146 León-López, 2019, Hydrolyzed collagen-sources and applications, Molecules, 24 Malafaya, 2007, Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications, Adv Drug Deliv Rev, 59, 207, 10.1016/j.addr.2007.03.012 Fujimura, 1995, Experimental studies on bone inducing activity of composites of atelopeptide type I collagen as a carrier for ectopic osteoinduction by rhBMP-2, Biochem Biophys Res Commun, 208, 316, 10.1006/bbrc.1995.1340 Yoshida, 1998, Osteoinduction capability of recombinant human bone morphogenetic protein-2 in intramuscular and subcutaneous sites: an experimental study, J Craniomaxillofac Surg, 26, 112, 10.1016/S1010-5182(98)80050-4 Wikesjö, 1999, Periodontal repair in dogs: effect of rhBMP-2 concentration on regeneration of alveolar bone and periodontal attachment, J Clin Periodontol, 26, 392, 10.1034/j.1600-051X.1999.260610.x Choi, 2002, Effect of recombinant human bone morphogenetic protein-2/absorbable collagen sponge (rhBMP-2/ACS) on healing in 3-wall intrabony defects in dogs, J Periodontol, 73, 63, 10.1902/jop.2002.73.1.63 de Freitas, 2015, Alveolar ridge and maxillary sinus augmentation using rhBMP-2: a systematic review, Clin Implant Dent Relat Res, 17, e192, 10.1111/cid.12156 Moslemi, 2018, Outcomes of alveolar ridge preservation with recombinant human bone morphogenetic protein-2: a systematic review, Implant Dent, 27, 351, 10.1097/ID.0000000000000722 King, 1998, Effect of two delivery systems for recombinant human bone morphogenetic protein-2 on periodontal regeneration in vivo, J Periodontal Res, 33, 226, 10.1111/j.1600-0765.1998.tb02194.x Fiorellini, 2005, Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation, J Periodontol, 76, 605, 10.1902/jop.2005.76.4.605 Shinohara, 2016, Bone healing capabilities of recombinant human bone morphogenetic protein-9 (rhBMP-9) with a chitosan or collagen carrier in rat calvarial defects, Dent Mater J, 35, 454, 10.4012/dmj.2015-242 Nakamura, 2017, Osteogenic potential of recombinant human bone morphogenetic protein-9/absorbable collagen sponge (rhBMP-9/ACS) in rat critical size calvarial defects, Clin Oral Investig, 21, 1659, 10.1007/s00784-016-1963-4 Fujioka-Kobayashi, 2017, Absorbable collagen sponges loaded with recombinant bone morphogenetic protein 9 induces greater osteoblast differentiation when compared to bone morphogenetic protein 2, Clin Exp Dent Res, 3, 32, 10.1002/cre2.55 Lee, 2020, Periodontal regeneration using recombinant human bone morphogenetic protein-2 and a bilayer collagen matrix, J Craniofac Surg, 31, 1602, 10.1097/SCS.0000000000006517 Kato, 2015, Combination of root surface modification with BMP-2 and collagen hydrogel scaffold implantation for periodontal healing in beagle dogs, Open Dent J, 9, 52, 10.2174/1874210601509010052 Takaoka, 1988, Ectopic bone induction on and in porous hydroxyapatite combined with collagen and bone morphogenetic protein, Clin Orthop Relat Res, 234, 250, 10.1097/00003086-198809000-00044 Ono, 1992, A study on bone induction on hydroxyapatite combined with bone morphogenetic protein, Plast Reconstr Surg, 90, 870, 10.1097/00006534-199211000-00023 Yoshida, 1999, Enhancement by recombinant human bone morphogenetic protein-2 of bone formation by means of porous hydroxyapatite in mandibular bone defects, J Dent Res, 78, 1505, 10.1177/00220345990780090401 Lu, 2012, Spatial immobilization of bone morphogenetic protein-4 in a collagen-PLGA hybrid scaffold for enhanced osteoinductivity, Biomaterials, 33, 6140, 10.1016/j.biomaterials.2012.05.038 Sotome, 2004, Synthesis and in vivo evaluation of a novel hydroxyapatite/collagen-alginate as a bone filler and a drug delivery carrier of bone morphogenetic protein, Mater Sci Eng C, 24, 341, 10.1016/j.msec.2003.12.003 Chen, 2014, Preparation and evaluation of collagen-silk fibroin/hydroxyapatite nanocomposites for bone tissue engineering, Int J Biol Macromol, 65, 1, 10.1016/j.ijbiomac.2014.01.003 Han, 2020, Enhanced healing of rat calvarial defects with 3D printed calcium-deficient hydroxyapatite/collagen/bone morphogenetic protein 2 scaffolds, J Mech Behav Biomed Mater, 108 Dien Bien, 2020, Original bone regeneration by low-dose recombinant human bone morphogenetic protein-2 carried on octacalcium phosphate collagen composite, J Hard Tissue Biol, 29, 123, 10.2485/jhtb.29.123 Polo, 2020, Synergism between recombinant human bone morphogenetic protein 2/absorbable collagen sponge and bone substitutes favors vertical bone augmentation and the resorption rate of the biomaterials: histomorphometric and 3D microcomputed tomography analysis, J Periodontol, 91, 1295, 10.1002/JPER.19-0571 Sawada, 2009, A trial of alveolar cleft bone regeneration by controlled release of bone morphogenetic protein: an experimental study in rabbits, Oral Surg Oral Med Oral Pathol Oral Radiol, 108, 812, 10.1016/j.tripleo.2009.06.040 Talwar, 2001, Effects of carrier release kinetics on bone morphogenetic protein-2-induced periodontal regeneration in vivo, J Clin Periodontol, 28, 340, 10.1034/j.1600-051x.2001.028004340.x Saito, 2009, Influence of residual bone on recombinant human bone morphogenetic protein-2-induced periodontal regeneration in experimental periodontitis in dogs, J Periodontol, 80, 961, 10.1902/jop.2009.080568 Ueki, 2003, The use of polylactic acid/polyglycolic acid copolymer and gelatin sponge complex containing human recombinant bone morphogenetic protein-2 following condylectomy in rabbits, J Craniomaxillofac Surg, 31, 107, 10.1016/S1010-5182(02)00187-7 Shimazu, 2006, Enhanced vertical alveolar bone augmentation by recombinant human bone morphogenetic protein-2 with a carrier in rats, J Oral Rehabil, 33, 609, 10.1111/j.1365-2842.2005.01593.x Kawakatsu, 2008, Effect of rhBMP-2 with PLGA/gelatin sponge type (PGS) carrier on alveolar ridge augmentation in dogs, J Oral Rehabil, 35, 647, 10.1111/j.1365-2842.2008.01850.x Sikkema, 2021, Hyaluronic‐acid‐based organic–inorganic composites for biomedical applications, Materials, 14 Hunt, 2001, Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs. A pilot study, J Periodontol, 72, 651, 10.1902/jop.2001.72.5.651 Kisiel, 2013, Improving the osteogenic potential of BMP-2 with hyaluronic acid hydrogel modified with integrin-specific fibronectin fragment, Biomaterials, 34, 704, 10.1016/j.biomaterials.2012.10.015 Docherty-Skogh, 2010, Bone morphogenetic protein-2 delivered by hyaluronan-based hydrogel induces massive bone formation and healing of cranial defects in minipigs, Plast Reconstr Surg, 125, 1383, 10.1097/PRS.0b013e3181d629dc Kim, 2007, Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells, Biomaterials, 28, 1830, 10.1016/j.biomaterials.2006.11.050 Bhakta, 2012, Hyaluronic acid-based hydrogels functionalized with heparin that support controlled release of bioactive BMP-2, Biomaterials, 33, 6113, 10.1016/j.biomaterials.2012.05.030 Park, 2006, Immobilization of bone morphogenetic protein-2 on a nanofibrous chitosan membrane for enhanced guided bone regeneration, Biotechnol Appl Biochem, 43, 17, 10.1042/BA20050075 Lee, 2019, Application of alginate microbeads as a carrier of bone morphogenetic protein-2 for bone regeneration, J Biomed Mater Res B Appl Biomater, 107, 286, 10.1002/jbm.b.34119 Priddy, 2014, Oxidized alginate hydrogels for bone morphogenetic protein-2 delivery in long bone defects, Acta Biomater, 10, 4390, 10.1016/j.actbio.2014.06.015 Huang, 2009, Fibronectin binds and enhances the activity of bone morphogenetic protein 1, J Biol Chem, 284, 25879, 10.1074/jbc.M109.024125 Han, 2005, Effect of a fibrin-fibronectin sealing system as a carrier for recombinant human bone morphogenetic protein-4 on bone formation in rat calvarial defects, J Periodontol, 76, 2216, 10.1902/jop.2005.76.12.2216 Maharana, 2015, Synthesis and characterization of poly(lactic acid) based graft copolymers, React Funct Polym, 93, 47, 10.1016/j.reactfunctpolym.2015.05.006 Bach, 1998, Uncertainty in Xenotransplantation: individual benefit versus collective risk, Nat Med, 4, 141, 10.1038/nm0298-141 Ginjupalli, 2017, Poly(α-hydroxy acid) based polymers: a review on material and degradation aspects, Polym Degrad Stab, 144, 520, 10.1016/j.polymdegradstab.2017.08.024 Lim, 2008, Processing technologies for poly(lactic acid), Prog Polym Sci, 33, 820, 10.1016/j.progpolymsci.2008.05.004 Miyamoto, 1992, Evaluation of polylactic acid homopolymers as carriers for bone morphogenetic protein, Clin Orthop Relat Res, 278, 274, 10.1097/00003086-199205000-00041 Cheng, 2019, Development of mussel-inspired 3D-printed poly (lactic acid) scaffold grafted with bone morphogenetic protein-2 for stimulating osteogenesis, J Mater Sci Mater Med, 30 Cao, 2012, Degradation and osteogenic potential of a novel poly(lactic acid)/nano-sized β-tricalcium phosphate scaffold, Int J Nanomed, 7, 5881, 10.2147/IJN.S38127 Kokubo, 2004, Long-term stability of bone tissues induced by an osteoinductive biomaterial, recombinant human bone morphogenetic protein-2 and a biodegradable carrier, Biomaterials, 25, 1795, 10.1016/j.biomaterials.2003.08.030 Higuchi, 1999, Bone regeneration by recombinant human bone morphogenetic protein-2 in rat mandibular defects. An experimental model of defect filling, J Periodontol, 70, 1026, 10.1902/jop.1999.70.9.1026 Kinoshita, 1997, Periodontal regeneration by application of recombinant human bone morphogenetic protein-2 to horizontal circumferential defects created by experimental periodontitis in beagle dogs, J Periodontol, 68, 103, 10.1902/jop.1997.68.2.103 Yokota, 2001, A new recombinant human bone morphogenetic protein-2 carrier for bone regeneration, Int J Pharm, 223, 69, 10.1016/S0378-5173(01)00728-1 Gutwald, 2010, Influence of rhBMP-2 on bone formation and osseointegration in different implant systems after sinus-floor elevation. An in vivo study on sheep, J Cranio-Maxillofac Surg, 38, 571, 10.1016/j.jcms.2010.02.010 Saito, 1999, New synthetic absorbable polymers as BMP carriers: plastic properties of poly-D,L-lactic acid-polyethylene glycol block copolymers, J Biomed Mater Res, 47, 104, 10.1002/(SICI)1097-4636(199910)47:1<104::AID-JBM15>3.0.CO;2-7 Saito, 2001, A biodegradable polymer as a cytokine delivery system for inducing bone formation, Nat Biotechnol, 19, 332, 10.1038/86715 Horvath, 2006, Solubility of structurally complicated materials: II. Bone, J Phys Chem Ref Data, 35, 1653, 10.1063/1.2360606 Szcześ, 2017, Synthesis of hydroxyapatite for biomedical applications, Adv Colloid Interface Sci, 249, 321, 10.1016/j.cis.2017.04.007 Dutta, 2015, Ceramic and non-ceramic hydroxyapatite as a bone graft material: a brief review, Ir J Med Sci, 184, 101, 10.1007/s11845-014-1199-8 Rizwan, 2020, In vitro evaluation of novel low-pressure spark plasma sintered HA-BG composite scaffolds for bone tissue engineering, RSC Adv, 10, 23813, 10.1039/D0RA04227G Lee, 2012, Comparative study of fusion rate induced by different dosages of Escherichia coli-derived recombinant human bone morphogenetic protein-2 using hydroxyapatite carrier, Spine J, 12, 239, 10.1016/j.spinee.2012.01.013 Urist, 1984, Beta-tricalcium phosphate delivery system for bone morphogenetic protein, Clin Orthop Relat Res, 187, 277, 10.1097/00003086-198407000-00042 Kawamura, 1987, Chondroosteogenetic response to crude bone matrix proteins bound to hydroxyapatite, Clin Orthop Relat Res, 217, 281, 10.1097/00003086-198704000-00030 Allegrini, 2003, The effects of bovine BMP associated to HA in maxillary sinus lifting in rabbits, Ann Anat, 185, 343, 10.1016/S0940-9602(03)80056-0 Kim, 2015, Efficacy of rhBMP-2/hydroxyapatite on sinus floor augmentation: a multicenter, randomized controlled clinical trial, J Dent Res, 94, 158S, 10.1177/0022034515594573 Shim, 2018, Comparative evaluation of recombinant human bone morphogenetic protein-2/Hydroxyapatite and bovine bone for new bone formation in alveolar ridge preservation, Implant Dent, 27, 623, 10.1097/ID.0000000000000814 Kim, 2017, Evaluation of bone healing using rhBMP-2 soaked hydroxyapatite in ridge augmentation: a prospective observational study, Maxillofac Plast Reconstr Surg, 39, 10.1186/s40902-017-0137-x Tsuruga, 1997, Pore size of porous hydroxyapatite as the cell-substratum controls bmp-induced osteogenesis, J Biochem, 121, 317, 10.1093/oxfordjournals.jbchem.a021589 Li, 2020, Design of hydroxyapatite bioceramics with micro-/nano-topographies to regulate the osteogenic activities of bone morphogenetic protein-2 and bone marrow stromal cells, Nanoscale, 12, 7284, 10.1039/C9NR10561A Xiong, 2015, BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects, Int J Nanomed, 10, 517, 10.2147/IJN.S74677 Zhou, 2018, Loading BMP-2 on nanostructured hydroxyapatite microspheres for rapid bone regeneration, Int J Nanomed, 13, 4083, 10.2147/IJN.S158280 Chen, 2020, Evaluation of BMP-2 and VEGF loaded 3D printed hydroxyapatite composite scaffolds with enhanced osteogenic capacity in vitro and in vivo, Mater Sci Eng C Mater Biol Appl, 112, 10.1016/j.msec.2020.110893 Walsh, 2019, Rapid healing of a critical-sized bone defect using a collagen-hydroxyapatite scaffold to facilitate low dose, combinatorial growth factor delivery, J Tissue Eng Regen Med, 13, 1843, 10.1002/term.2934 Daugela, 2018, Novel cellulose/hydroxyapatite scaffolds for bone tissue regeneration: in vitro and in vivo study, J Tissue Eng Regen Med, 12, 1195, 10.1002/term.2651 Destainville, 2003, Synthesis, characterization and thermal behavior of apatitic tricalcium phosphate, Mater Chem Phys, 1, 269, 10.1016/S0254-0584(02)00466-2 Kang, 2017, Synthesis and characterization of β-tricalcium phosphate derived from Haliotis sp. shells, Implant Dent, 26, 378, 10.1097/ID.0000000000000559 Lovasik, 2017, Anterior cervical discectomy and fusion: comparison of fusion, dysphagia, and complication rates between recombinant human bone morphogenetic protein-2 and beta-tricalcium phosphate, World Neurosurg, 97, 674, 10.1016/j.wneu.2016.10.088 Parker, 2017, Comparison of a calcium phosphate bone substitute with recombinant human bone morphogenetic protein-2: a prospective study of fusion rates, clinical outcomes and complications with 24-month follow-up, Eur Spine J, 26, 754, 10.1007/s00586-016-4927-0 Zétola, 2015, Use of rhBMP-2/β-TCP for interpositional vertical grafting augmentation: 5.5-year follow-up clinically and histologically, Implant Dent, 24, 349 Ohyama, 2004, b-Tricalcium phosphate combined with recombinant human bone morphogenetic protein-2: a substitute for autograft, used for packing interbody fusion cages in the canine lumbar spine, Neurol Med Chir, 44, 234, 10.2176/nmc.44.234 Wu, 1992, Enhanced osteoinduction by intramuscular grafting of BMP-B-TCP compound pellets into murine models, Arch Histol Cytol, 55, 97, 10.1679/aohc.55.97 Laffargue, 1999, Evaluation of human recombinant bone morphogenetic protein-2-loaded tricalcium phosphate implants in rabbits’ bone defects, Bone, 25, 55S, 10.1016/S8756-3282(99)00134-9 Ahn, 2003, Effect of recombinant human bone morphogenetic protein-4 with carriers in rat calvarial defects, J Periodontol, 74, 787, 10.1902/jop.2003.74.6.787 Pang, 2004, Effect of recombinant human bone morphogenetic protein-4 dose on bone formation in a rat calvarial defect model, J Periodontol, 75, 1364, 10.1902/jop.2004.75.10.1364 Wei, 2020, Dose effects of slow-released bone morphogenetic protein-2 functionalized β-tricalcium phosphate in repairing critical-sized bone defects, Tissue Eng Part A, 26, 120, 10.1089/ten.tea.2019.0161 Fang, 2018, Injectable thermosensitive alginate/β-tricalcium phosphate/aspirin hydrogels for bone augmentation, J Biomed Mater Res B Appl Biomater, 106, 1739, 10.1002/jbm.b.33982 Park, 2021, Three-dimensionally printed polycaprolactone/beta-tricalcium phosphate scaffold was more effective as an rhBMP-2 carrier for new bone formation than polycaprolactone alone, J Biomed Mater Res A, 109, 840, 10.1002/jbm.a.37075 Jung, 2008, Bone morphogenetic protein-2 enhances bone formation when delivered by a synthetic matrix containing hydroxyapatite/tricalciumphosphate, Clin Oral Implants Res, 19, 188, 10.1111/j.1600-0501.2007.01431.x Gruber, 2014, Mandibular reconstruction using a calcium phosphate/polyethylene glycol hydrogel carrier with BMP-2, J Clin Periodontol, 41, 820, 10.1111/jcpe.12264 Pina, 2015, Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review, Adv Mater, 27, 1143, 10.1002/adma.201403354 Ebrahimi, 2017, Biphasic calcium phosphates bioceramics (HA/TCP): Concept, physicochemical properties and the impact of standardization of study protocols in biomaterials research, Mater Sci Eng C Mater Biol Appl, 71, 1293, 10.1016/j.msec.2016.11.039 Nery, 1990, A veterans administration cooperative study of biphasic calcium phosphate ceramic in periodontal osseous defects, J Periodontol, 61, 737, 10.1902/jop.1990.61.12.737 Shuang, 2016, In vitro characterization of an osteoinductive biphasic calcium phosphate in combination with recombinant BMP2, BMC Oral Health, 17 Jeong, 2015, Repair of cranial bone defects using rhBMP2 and submicron particle of biphasic calcium phosphate ceramics with through-hole, Biomed Res Int, 10.1155/2015/926291 Naujokat, 2020, Osseointegration of dental implants in ectopic engineered bone in three different scaffold materials, Int J Oral Maxillofac Surg, 49, 135, 10.1016/j.ijom.2019.04.005 Zhang, 2016, Addition of a synthetically fabricated osteoinductive biphasic calcium phosphate bone graft to BMP2 improves new bone formation, Clin Implant Dent Relat Res, 18, 1238, 10.1111/cid.12384 You, 2016, Bone regenerative efficacy of limited-dose Escherichia coli-derived rhBMP-2 with biphasic calcium phosphate carrier in rabbit calvarial defect model, Implant Dent, 25, 16, 10.1097/ID.0000000000000364 Al-Qutub, 2016, Guided bone regeneration using biphasic calcium phosphate with adjunct recombinant human bone morphogenetic protein-2 with and without collagen membrane in standardized calvarial defects in rats: a histologic and biomechanical analysis, Int J Periodontics Restor Dent, 36, s11, 10.11607/prd.2376 Jung, 2015, Comparative analysis of carrier systems for delivering bone morphogenetic proteins, J Periodontal Implant Sci, 45, 136, 10.5051/jpis.2015.45.4.136 Kim, 2015, Prospective randomized, controlled trial of sinus grafting using Escherichia-coli-produced rhBMP-2 with a biphasic calcium phosphate carrier compared to deproteinized bovine bone, Clin Oral Implants Res, 26, 1361, 10.1111/clr.12471 Jo, 2019, A randomized controlled clinical trial evaluating efficacy and adverse events of different types of recombinant human bone morphogenetic protein-2 delivery systems for alveolar ridge preservation, Clin Oral Implants Res, 30, 396, 10.1111/clr.13423 Ebrahimi, 2012, Fabrication and characterization of novel nano hydroxyapatite/β- tricalcium phosphate scaffolds in three different composition ratios, J Biomed Mater Res A, 100, 2260, 10.1002/jbm.a.34160 Yun, 2014, Influence of bone morphogenetic protein and proportion of hydroxyapatite on new bone formation in biphasic calcium phosphate graft: two pilot studies in animal bony defect model, J Craniomaxillofac Surg, 42, 1909, 10.1016/j.jcms.2014.07.011 Hong, 2016, A high concentration of recombinant human bone morphogenetic protein-2 induces low-efficacy bone regeneration in sinus augmentation: a histomorphometric analysis in rabbits, Clin Oral Implants Res, 27, e199, 10.1111/clr.12603 Kim, 2016, Increased osteoinductivity and mineralization by minimal concentration of bone morphogenetic protein-2 loaded onto biphasic calcium phosphate in a rabbit sinus, J Periodontal Implant Sci, 46, 350, 10.5051/jpis.2016.46.5.350 Chung, 2016, Evaluation of different combinations of biphasic calcium phosphate and growth factors for bone formation in calvarial defects in a rabbit model, Int J Periodontics Restor Dent, 36, 10.11607/prd.2633 Kim, 2015, Acceleration of bone regeneration by BMP-2-loaded collagenated biphasic calcium phosphate in rabbit sinus, Clin Implant Dent Relat Res, 17, 1103, 10.1111/cid.12223 Zheng, 2014, A novel BMP2-coprecipitated, layer-by-layer assembled biomimetic calcium phosphate particle: a biodegradable and highly efficient osteoinducer, Clin Implant Dent Relat Res, 16, 643, 10.1111/cid.12050 Wei, 2019, Periodontal regeneration using bone morphogenetic protein 2 incorporated biomimetic calcium phosphate in conjunction with barrier membrane: A pre-clinical study in dogs, J Clin Periodontol, 46, 1254, 10.1111/jcpe.13195 Chao, 2021, Effects of low-dose rhBMP-2 on peri-implant ridge augmentation in a canine model, J Clin Periodontol, 48, 734, 10.1111/jcpe.13440 Hamlet, 2017, 3-Dimensional functionalized polycaprolactone-hyaluronic acid hydrogel constructs for bone tissue engineering, J Clin Periodontol, 44, 428, 10.1111/jcpe.12686 Park, 2005, Injectable bone using chitosan-alginate gel/mesenchymal stem cells/BMP-2 composites, J Craniomaxillofac Surg, 33, 50, 10.1016/j.jcms.2004.05.011 Deng, 2019, Experimental study of rhBMP-2 chitosan nano-sustained release carrier-loaded PLGA/nHA scaffolds to construct mandibular tissue-engineered bone, Arch Oral Biol, 102, 16, 10.1016/j.archoralbio.2019.03.023 Yilgor, 2009, Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering, Biomaterials, 30, 3551, 10.1016/j.biomaterials.2009.03.024 Yilgor, 2010, Effect of scaffold architecture and BMP-2/BMP-7 delivery on in vitro bone regeneration, J Mater Sci Mater Med, 21, 2999, 10.1007/s10856-010-4150-1 Tröltzsch, 2017, Repair of large saddle defects of the mandibular ridge using dual growth factor release—an experimental pilot study in minipigs, J Clin Periodontol, 44, 854, 10.1111/jcpe.12739 Bastami, 2017, Fabrication of a three-dimensional β-tricalcium-phosphate/gelatin containing chitosan-based nanoparticles for sustained release of bone morphogenetic protein-2: Implication for bone tissue engineering, Mater Sci Eng C Mater Biol Appl, 72, 481, 10.1016/j.msec.2016.10.084 Talley, 2018, Injectable, compression-resistant polymer/ceramic composite bone grafts promote lateral ridge augmentation without protective mesh in a canine model, Clin Oral Implants Res, 29, 592, 10.1111/clr.13257 Boller, 2020, Compression-resistant polymer/ceramic composite scaffolds augmented with rhBMP-2 promote new bone formation in a nonhuman primate mandibular ridge augmentation model, Int J Oral Maxillofac Implants, 35, 616, 10.11607/jomi.7877 Fischer, 2011, Future of local bone regeneration - protein versus gene therapy, J Craniomaxillofac Surg, 39, 54, 10.1016/j.jcms.2010.03.016 Gupta, 2015, Gene therapy in dentistry: tool of genetic engineering. Revisited, Arch Oral Biol, 60, 439, 10.1016/j.archoralbio.2014.11.018 Kirker-Head, 2000, Potential applications and delivery strategies for bone morphogenetic proteins, Adv Drug Deliv Rev, 43, 65, 10.1016/S0169-409X(00)00078-8 Franceschi, 2004, Gene therapy approaches for bone regeneration, Cells Tissues Organs, vol. 176, 95, 10.1159/000075031 Jin, 2003, Gene therapy of bone morphogenetic protein for periodontal tissue engineering, J Periodontol, 74, 202, 10.1902/jop.2003.74.2.202 Shin, 2010, Ex vivo bone morphogenetic protein-2 gene delivery using gingival fibroblasts promotes bone regeneration in rats, J Clin Periodontol, 37, 305, 10.1111/j.1600-051X.2009.01522.x Dunn, 2005, BMP gene delivery for alveolar bone engineering at dental implant defects, Mol Ther, 11, 294, 10.1016/j.ymthe.2004.10.005