Preclinical Evaluation of Bioactive Scaffolds for the Treatment of Mandibular Critical-Sized Bone Defects: A Systematic Review
Source abstract
Abstract
This systematic review evaluated current in vivo research on regenerating critical-sized mandibular defects and discussed methodologies for mandibular bone tissue engineering. Out of the 3650 articles initially retrieved, 88 studies were included, and all studies that used a scaffold reported increased bone formation compared to negative controls. Combining scaffolds with growth factors and mesenchymal stem cells improved bone formation and healing. Bone morphogenic proteins were widely used and promoted significant bone formation compared to controls. However, discrepancies between studies exist due to the various methodologies and outcome measures used. The use of scaffolds with bioactive molecules and/or progenitor cells enhances success in mandibular bone engineering. Scaffold-based mandibular bone tissue engineering could be introduced into clinical practice due to its proven safety, convenience, and cost-effectiveness.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Bone Tissue Engineering Materials · Periodontal Regeneration and Treatments · Bone and Dental Protein Studies
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia
Dental Clinic, Military Medical Academy, University of Defence, Crnotravska 17, 11000 Belgrade, Serbia
Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia
References (100+)
Show source-provided references
1. Vujovic, S., Desnica, J., Stanisic, D., Ognjanovic, I., Stevanovic, M., and Rosic, G. (2022). Applications of Biodegradable Magnesium-Based Materials in Reconstructive Oral and Maxillofacial Surgery: A Review. Molecules, 27.10.3390/molecules27175529 ↗
2. Systematic scoping review of mandibular bone tissue engineering10.1016/j.bjoms.2020.03.016 ↗
3. Individual construction of freeform-fabricated polycaprolactone scaffolds for osteogenesis10.1515/bmt-2016-0005 ↗
4. Bone tissue engineering: Recent advances and challenges10.1615/CritRevBiomedEng.v40.i5.10 ↗
5. Current concerns regarding healing of bone defects10.13172/2050-2303-2-2-374 ↗
6. Jamari, J., Ammarullah, M.I., Saad, A.P.M., Syahrom, A., Uddin, M., van der Heide, E., and Basri, H. (2021). The Effect of Bottom Profile Dimples on the Femoral Head on Wear in Metal-on-Metal Total Hip Arthroplasty. J. Funct. Biomater., 12.10.3390/jfb12020038 ↗
7. Injectable biomaterials for regenerating complex craniofacial tissues10.1002/adma.200802009 ↗
8. Biomimetic supramolecular designs for the controlled release of growth factors in bone regeneration10.1016/j.addr.2015.08.003 ↗
9. Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?10.1159/000469704 ↗
10. Biomaterials for Craniofacial Bone Regeneration10.1016/j.cden.2017.06.003 ↗
11. Putra, R.U., Basri, H., Prakoso, A.T., Chandra, H., Ammarullah, M.I., Akbar, I., Syahrom, A., and Kamarul, T. (2023). Level of Activity Changes Increases the Fatigue Life of the Porous Magnesium Scaffold, as Observed in Dynamic Immersion Tests, over Time. Sustainability, 15.10.3390/su15010823 ↗
12. Stevanovic, M., Vujovic, S., Stanisic, D., Desnica, J., and Ognjanovic, I. (2022). The Use of Newly Synthesized Composite Scaffolds for Bone Regeneration—A Review of Literature. Exp. Appl. Biomed. Res. EABR.10.2478/sjecr-2021-0071 ↗
13. Venkataiah, V.S., Yahata, Y., Kitagawa, A., Inagaki, M., Kakiuchi, Y., Nakano, M., Suzuki, S., Handa, K., and Saito, M. (2021). Clinical Applications of Cell-Scaffold Constructs for Bone Regeneration Therapy. Cells, 10.10.3390/cells10102687 ↗
14. Valdoz, J.C., Johnson, B.C., Jacobs, D.J., Franks, N.A., Dodson, E.L., Sanders, C., Cribbs, C.G., and Van Ry, P.M. (2021). The ECM: To Scaffold, or Not to Scaffold, That Is the Question. Int. J. Mol. Sci., 22.10.3390/ijms222312690 ↗
15. Design, materials, and mechanobiology of biodegradable scaffolds for bone tissue engineering10.1155/2015/729076 ↗
16. Mechanisms of guided bone regeneration: A review10.2174/1874210601408010056 ↗
17. Orthopaedic applications of bone graft & graft substitutes: A review
18. Expression of bone morphogenetic protein 2 and fibroblast growth factor 2 during bone regeneration using different implant materials as an onlay bone graft in rabbit mandibles10.1016/j.tripleo.2006.01.019 ↗
19. Natural graft tissues and synthetic biomaterials for periodontal and alveolar bone reconstructive applications: A review10.1186/s40824-017-0095-5 ↗
20. Guided bone regeneration: Materials and biological mechanisms revisited10.1111/eos.12364 ↗
21. ALLOGRAFT BONE: The influence of processing on safety and performance10.1016/S0030-5898(05)70110-3 ↗
22. The enhancement of osteogenic capacity in a synthetic BMP-2 derived peptide coated mineralized collagen composite in the treatment of the mandibular defects
23. Restoration of critical-size defects in the rabbit mandible using porous nanohydroxyapatite-polyamide scaffolds10.1089/ten.tea.2011.0503 ↗
24. Mineralised Collagen Scaffolds Loaded with Stromal Cell-derived Factor-1 Improve Mandibular Bone Regeneration
25. Dual delivery of BMP-2 and bFGF from a new nano-composite scaffold, loaded with vascular stents for large-size mandibular defect regeneration10.3390/ijms140612714 ↗
26. Critical-sized mandibular defect reconstruction using human dental pulp stem cells in a xenograft model-clinical, radiological, and histological evaluation10.1007/s10006-020-00862-7 ↗
27. Delivery of growth factors using a smart porous nanocomposite scaffold to repair a mandibular bone defect10.1021/bm401911p ↗
28. Enhancement of bone formation by BMP-7 transduced MSCs on biomimetic nano-hydroxyapatite/polyamide composite scaffolds in repair of mandibular defects10.1002/jbm.a.32926 ↗
29. The use of tissue-engineered bone with human bone morphogenetic protein-4-modified bone-marrow stromal cells in repairing mandibular defects in rabbits10.1016/j.ijom.2006.07.005 ↗
30. Combination of beta-TCP and BMP-2 gene-modified bMSCs to heal critical size mandibular defects in rats10.1111/j.1601-0825.2009.01602.x ↗
31. Bone marrow-derived osteoblasts seeded into porous beta-tricalcium phosphate to repair segmental defect in canine’s mandibula
32. Osteogenesis of mineralized collagen bone graft modified by PLA and calcium sulfate hemihydrate: In vivo study10.1177/0885328211433618 ↗
33. Porous Nanohydroxyapatite/Collagen Scaffolds Loading Insulin PLGA Particles for Restoration of Critical Size Bone Defect10.1021/acsami.6b13566 ↗
34. Restoration of mandibular bone defects with demineralized bone matrix combined with three-dimensional cultured bone marrow-derived mesenchymal stem cells in minipig models10.1007/s10856-018-6152-3 ↗
35. Bone regeneration of minipig mandibular defect by adipose derived mesenchymal stem cells seeded tri-calcium phosphate-poly(D,L-lactide-co-glycolide) scaffolds10.1038/s41598-020-59038-8 ↗
36. Stevanovic, M., Selakovic, D., Vasovic, M., Ljujic, B., Zivanovic, S., Papic, M., Zivanovic, M., Milivojevic, N., Mijovic, M., and Tabakovic, S.Z. (2022). Comparison of Hydroxyapatite/Poly(lactide-co-glycolide) and Hydroxyapatite/Polyethyleneimine Composite Scaffolds in Bone Regeneration of pigs Mandibular Critical Size Defects: In Vivo Study. Molecules, 27.10.3390/molecules27051694 ↗
37. Experimental study on reconstruction of segmental mandible defects using tissue engineered bone combined bone marrow stromal cells with three-dimensional tricalcium phosphate10.1097/scs.0b013e31806901f5 ↗
38. Repair of canine mandibular bone defects with bone marrow stromal cells and porous beta-tricalcium phosphate10.1016/j.biomaterials.2006.10.015 ↗
39. Transplantation of dedifferentiated fat cells combined with a biodegradable type I collagen-recombinant peptide scaffold for critical-size bone defects in rats10.2334/josnusd.18-0458 ↗
40. Biomimetic scaffolds facilitate healing of critical-sized segmental mandibular defects10.1016/j.amjoto.2014.06.007 ↗
41. Enhanced Mandibular Bone Repair by Combined Treatment of Bone Morphogenetic Protein 2 and Small-Molecule Phenamil10.1089/ten.tea.2016.0308 ↗
42. In vivo bone formation by human bone marrow stromal cells: Reconstruction of the mouse calvarium and mandible10.1634/stemcells.2005-0567 ↗
43. Reconstructing jaw defects with MSCs and PLGA-encapsulated growth factors
44. Three dimensionally printed bioactive ceramic scaffold osseoconduction across critical-sized mandibular defects10.1016/j.jss.2017.10.027 ↗
45. Recombinant human bone morphogenetic protein 2 combined with an osteoconductive bulking agent for mandibular continuity defects in nonhuman primates10.1016/j.joms.2011.02.088 ↗
46. Mandibular reconstruction using bone morphogenetic protein 2: Long-term follow-up in a canine model10.1097/00005537-199909000-00023 ↗
47. The effect of platelet-rich fibrin exudate addition to porous poly(lactic-co-glycolic acid) scaffold in bone healing: An in vivo study10.1002/jbm.b.34478 ↗
48. Tissue-engineered bone with 3-dimensionally printed β-tricalcium phosphate and polycaprolactone scaffolds and early implantation: An in vivo pilot study in a porcine mandible model10.1016/j.joms.2015.01.021 ↗
49. Adipose-derived stem cells and BMP-2 delivery in chitosan-based 3D constructs to enhance bone regeneration in a rat mandibular defect model10.1089/ten.tea.2013.0523 ↗
50. Poly(lactic-co-glycolide) polymer constructs cross-linked with human BMP-6 and VEGF protein significantly enhance rat mandible defect repair10.1007/s00441-015-2301-x ↗
51. Bone morphogenetic protein-2-impregnated biomimetic scaffolds successfully induce bone healing in a marginal mandibular defect10.1002/lary.23782 ↗
52. Comparison of BMP-2 and -4 for rat mandibular bone regeneration at various doses10.1111/j.1601-6343.2005.00349.x ↗
53. Bone regeneration in the rat mandible with bone morphogenetic protein-2: A comparison of two carriers10.1016/j.otohns.2004.09.137 ↗
54. Defect repair in the rat mandible with bone morphogenic proteins and marrow cells10.1001/archfaci.5.1.103 ↗
55. Bone regeneration using rhBMP-2 induction in hemimandibulectomy type defects of elderly sub-human primates10.1007/s10561-005-2242-9 ↗
56. Continuous delivery of rhBMP2 and rhVEGF165 at a certain ratio enhances bone formation in mandibular defects over the delivery of rhBMP2 alone--An experimental study in rats10.1016/j.jconrel.2015.10.032 ↗
57. Do we need retarded delivery of bone growth factors in facial bone repair? An experimental study in rats10.22203/eCM.v034a11 ↗
58. BMP-2 and bFGF in an irradiated bone model10.1016/j.jcms.2007.09.001 ↗
59. Sandwich-Like Nanofibrous Scaffolds for Bone Tissue Regeneration10.1021/acsami.9b06359 ↗
60. Mandibular bone repair by implantation of rhBMP-2 in a slow release carrier of polylactic acid--an experimental study in rats10.1016/j.biomaterials.2007.09.019 ↗
61. Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer: A comparison of adenoviral vectors and liposomes10.1038/sj.gt.3301960 ↗
62. Reconstruction of critical-size mandibular defects in immunoincompetent rats with human adipose-derived stromal cells10.1016/j.jcms.2013.04.002 ↗
63. Carboxymethylcellulose-stabilized collagenous rhOP-1 device-a novel carrier biomaterial for the repair of mandibular continuity defects10.1002/jbm.a.10129 ↗
64. Use of cultivated osteoprogenitor cells to increase bone formation in segmental mandibular defects: An experimental pilot study in sheep10.1054/ijom.2001.0164 ↗
65. A collagen membrane containing osteogenic protein-1 facilitates bone regeneration in a rat mandibular bone defect10.1016/j.archoralbio.2017.09.005 ↗
66. Functional reconstruction of the non-human primate mandible using recombinant human bone morphogenetic protein-210.1054/ijom.2001.0207 ↗
67. Autogenous injectable bone for regeneration with mesenchymal stem cells and platelet-rich plasma: Tissue-engineered bone regeneration10.1089/1076327041348284 ↗
68. Mandibular reconstruction using a combination graft of rhBMP-2 with bone marrow cells expanded in vitro10.1097/01.prs.0000200069.81973.49 ↗
69. Dipyridamole Augments Three-Dimensionally Printed Bioactive Ceramic Scaffolds to Regenerate Craniofacial Bone10.1097/PRS.0000000000005531 ↗
70. Reconstruction of the primate mandible with a combination graft of recombinant human bone morphogenetic protein-2 and bone marrow10.1053/joms.2001.19286 ↗
71. The use of TriCalcium Phosphate (TCP) and stem cells for the regeneration of osteoperiosteal critical-size mandibular bony defects, an in vitro and preclinical study10.1016/j.jcms.2013.12.006 ↗
72. Histological assessment of bioengineered new bone in repairing osteoperiosteal mandibular defects in sheep using recombinant human bone morphogenetic protein-710.1016/j.bjoms.2004.05.005 ↗
73. Mechanical evaluation of mandibular defects reconstructed using osteogenic protein-1 (rhOP-1) in a sheep model: A critical analysis10.1016/j.ijom.2004.09.008 ↗
74. Mechanical testing of recombinant human bone morphogenetic protein-7 regenerated bone in sheep mandibles10.1243/0954411042632135 ↗
75. Mandibular reconstruction in the rabbit using beta-tricalcium phosphate (β-TCP) scaffolding and recombinant bone morphogenetic protein 7 (rhBMP-7)—Histological, radiographic and mechanical evaluations10.1016/j.jcms.2012.03.005 ↗
76. Experimental study of rhBMP-2 chitosan nano-sustained release carrier-loaded PLGA/nHA scaffolds to construct mandibular tissue-engineered bone10.1016/j.archoralbio.2019.03.023 ↗
77. Effect of bone marrow-derived stem cells and bone morphogenetic protein-2 on treatment of osteoradionecrosis in a rat model10.1016/j.jcms.2015.06.035 ↗
78. 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 model10.1016/j.jcms.2014.07.011 ↗
79. Enhanced regeneration of rabbit mandibular defects through a combined treatment of electrical stimulation and rhBMP-2 application10.1007/s11517-013-1106-x ↗
80. Local delivery of recombinant human FGF7 enhances bone formation in rat mandible defects10.1007/s00774-016-0784-5 ↗
81. Transplantation of stem cells from human exfoliated deciduous teeth for bone regeneration in the dog mandibular defect10.4252/wjsc.v6.i4.505 ↗
82. The effect of PCL-TCP scaffold loaded with mesenchymal stem cells on vertical bone augmentation in dog mandible: A preliminary report10.1002/jbm.b.32889 ↗
83. Repair of rat mandibular bone defects by alveolar osteoblasts in a novel plasma-derived albumin scaffold10.1089/ten.tea.2009.0517 ↗
84. Repair of segmental mandibular bone defects in sheep using bone marrow stromal cells and autologous serum scaffold: A pilot study10.1111/jcpe.12480 ↗
85. A 3D-printed polycaprolactone/β-tricalcium phosphate mandibular prosthesis: A pilot animal study10.1002/lary.27908 ↗
86. Osteoinductivity of Porous Biphasic Calcium Phosphate Ceramic Spheres with Nanocrystalline and Their Efficacy in Guiding Bone Regeneration10.1021/acsami.8b18525 ↗
87. Bone repair in rat mandible by rhBMP-2 associated with two carriers10.1016/j.micron.2007.03.008 ↗
88. Difference in soft tissue response between immediate and delayed delivery suggests a new mechanism for recombinant human bone morphogenetic protein 2 action in large segmental bone defects10.1089/ten.tea.2011.0148 ↗
89. The copolymer of epsilon-caprolactone-lactide and tricalcium phosphate does not enhance bone growth in mandibular defect of sheep10.1007/s10856-006-6817-1 ↗
90. Mandibular segmental defect regenerated with macroporous biphasic calcium phosphate, collagen membrane, and bone marrow graft in dogs10.1001/archoto.2010.173 ↗
91. Mandibular defect repair by TGF-beta and IGF-1 released from a biodegradable osteoconductive hydrogel10.1016/j.jcms.2004.09.003 ↗
92. The Use of Sequential VEGF- and BMP2-Releasing Biodegradable Scaffolds in Rabbit Mandibular Defects10.1016/j.joms.2016.08.020 ↗
93. Localized low-dose rhBMP-2 is effective at promoting bone regeneration in mandibular segmental defects10.1002/jbm.b.34241 ↗
94. Pervasion of beta-tricalcium phosphate with nanodiamond particles yields efficient and safe bone replacement material amenable for biofunctionalization and application in large-size osseous defect healing10.1016/j.nano.2018.08.015 ↗
95. Bone regeneration in critically sized rat mandible defects through the endochondral pathway using hydroxyapatite-coated 3D-printed Ti6Al4V scaffolds10.1039/C8RA06508J ↗
96. Osteogenesis ability of CAD-CAM biodegradable polylactic acid scaffolds for reconstruction of jaw defects10.1016/j.prosdent.2018.03.033 ↗
97. Antibody-Mediated Osseous Regeneration for Bone Tissue Engineering in Canine Segmental Defects10.1155/2018/9508721 ↗
98. Effect of expanded bone marrow-derived osteoprogenitor cells seeded into polycaprolactone/tricalcium phosphate scaffolds in new bone regeneration of rabbit mandibular defects10.1007/s10856-018-6030-z ↗
99. In vivo evaluation of chitosan-glycerol gel scaffolds seeded with stem cells for full-thickness mandibular bone regeneration10.2334/josnusd.16-0235 ↗
100. Bone morphogenetic protein-2 sustained delivery by hydrogels with microspheres repairs rabbit mandibular defects10.1007/s13770-016-9123-0 ↗