In vivo validation of osteoinductivity and biocompatibility of BMP-2 enriched calcium phosphate cement alongside retrospective description of its clinical adverse events.
Adverse events
BMP-2
Calcium phosphate cement
Maxillofacial surgery
Journal
International journal of implant dentistry
ISSN: 2198-4034
Titre abrégé: Int J Implant Dent
Pays: Germany
ID NLM: 101676532
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
31
07
2024
accepted:
17
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
Although bone morphogenetic protein-2 (BMP-2) possesses potent osteoinductivity, there have been some concerns on the safety of BMP-2 and BMP-2-incorporated bone substitutes used for bone formation. On the other hand, BMP-2-loaded calcium phosphate cement (BMP-2@CPC) has been developed and used for bone regeneration in oral implantology. Therefore, this study aims to investigate this product's biocompatibility and clinical safety after being used in maxillofacial surgery. A rat model was employed to assess the osteoinduction and biocompatibility of BMP-2@CPC. Further, a retrospective investigation was carried out: 110 patients who received BMP-2@CPC treatment after their maxillofacial surgery were recruited to describe relative adverse events. In vivo, BMP-2@CPC showed a significantly higher mean bone volume density and osteoblasts volume density (15 ± 2% and 3 ± 1%)than those of the CPC group (p < 0.05) after being implanted in the dorsal area of rats. Regarding biocompatibility, the mean fibrous tissue volume density was significantly lower in the BMP-2@CPC group (20 ± 5% compared to 31 ± 6%, p = 0.026). The retrospective clinical study showed that only five mild/moderate adverse events were identified in four patients based on the medical records of 110 patients, including swelling, bony mass, and wound dehiscence. This adverse event occurrence was not affected by gender, age, the dose of filled materials, and operations in the study (p > 0.05). BMP-2-loaded CPC has osteoinductivity and more promising biocompatibility than pure CPC. However, its degradation is slower than CPC. The safety of BMP-2-loaded CPC with 0.5 or 1 mg BMP-2 is promising in oral maxillofacial surgery. This study confirmed the promising safety of this BMP-2 incorporated CPC used in dental clinical practice, which can promote its reassuring application for dental implant placement in bone insufficient areas.
Identifiants
pubmed: 39472366
doi: 10.1186/s40729-024-00567-6
pii: 10.1186/s40729-024-00567-6
doi:
Substances chimiques
Bone Morphogenetic Protein 2
0
Calcium Phosphates
0
Biocompatible Materials
0
Bone Cements
0
calcium phosphate
97Z1WI3NDX
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
47Subventions
Organisme : Dutch ZonMW grant on LSH 2TREAT
ID : No. 436001004
Informations de copyright
© 2024. The Author(s).
Références
Kolambkar YM, Boerckel JD, Dupont KM, Bajin M, Huebsch N, Mooney DJ, et al. Spatiotemporal delivery of bone morphogenetic protein enhances functional repair of segmental bone defects. Bone. 2011;49:485–92.
doi: 10.1016/j.bone.2011.05.010
Sakkas A, Wilde F, Heufelder M, Winter K, Schramm A. Autogenous bone grafts in oral implantology-is it still a “gold standard”? A consecutive review of 279 patients with 456 clinical procedures. Int J Implant Dent. 2017;3:23.
doi: 10.1186/s40729-017-0084-4
Wei L, Miron RJ, Shi B, Zhang Y. Osteoinductive and osteopromotive variability among different demineralized bone allografts. Clin Implant Dent Relat Res. 2015;17:533–42.
doi: 10.1111/cid.12118
Diaz-Rodriguez P, Sanchez M, Landin M. Drug-loaded biomimetic ceramics for tissue engineering. Pharmaceutics. 2018;10:272.
doi: 10.3390/pharmaceutics10040272
Lin D, Zhang J, Bai F, Cao X, Fan C, Yuan Y, et al. Fabrication and clinical application of easy-to-operate pre-cured CPC/rhBMP-2 micro-scaffolds for bone regeneration. Am J Transl Res. 2016;8:1379–96.
Grafe IA, Baier M, Nöldge G, Weiss C, Da Fonseca K, Hillmeier J, et al. Calcium-phosphate and polymethylmethacrylate cement in long-term outcome after kyphoplasty of painful osteoporotic vertebral fractures. Spine (Phila Pa 1976). 2008;33:1284–90.
doi: 10.1097/BRS.0b013e3181714a84
Ambard AJ, Mueninghoff L. Calcium phosphate cement: review of mechanical and biological properties. J Prosthodont. 2006;15:321–8.
doi: 10.1111/j.1532-849X.2006.00129.x
Frankenburg EP, Goldstein SA, Bauer TW, Harris SA, Poser RD. Biomechanical and histological evaluation of a calcium phosphate cement. J Bone Joint Surg Am. 1998;80:1112–24.
doi: 10.2106/00004623-199808000-00004
Zhang J, Zhou H, Yang K, Yuan Y, Liu C. RhBMP-2-loaded calcium silicate/calcium phosphate cement scaffold with hierarchically porous structure for enhanced bone tissue regeneration. Biomaterials. 2013;34:9381–92.
doi: 10.1016/j.biomaterials.2013.08.059
Wozney JM. The bone morphogenetic protein family and osteogenesis. Mol Reprod Dev. 1992;32:160–7.
doi: 10.1002/mrd.1080320212
Burkus JK, Gornet MF, Dickman CA, Zdeblick TA. Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages. J Spinal Disord Tech. 2002;15:337–49.
doi: 10.1097/00024720-200210000-00001
Alonso N, Risso GH, Denadai R, Raposo-Amaral CE. Effect of maxillary alveolar reconstruction on nasal symmetry of cleft lip and palate patients: a study comparing iliac crest bone graft and recombinant human bone morphogenetic protein-2. J Plast Reconstr Aesthet Surg JPRAS. 2014;67:1201–8.
doi: 10.1016/j.bjps.2014.05.014
Ramly EP, Alfonso AR, Kantar RS, Wang MM, Siso JRD, Ibrahim A, et al. Safety and efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) in craniofacial surgery. Plast Reconstr Surg Glob Open. 2019;7: e2347.
doi: 10.1097/GOX.0000000000002347
Hunziker EB, Enggist L, Küffer A, Buser D, Liu Y. Osseointegration: the slow delivery of BMP-2 enhances osteoinductivity. Bone. 2012;51:98.
doi: 10.1016/j.bone.2012.04.004
Hashimoto K, Kaito T, Furuya M, Seno S, Okuzaki D, Kikuta J, et al. In vivo dynamic analysis of BMP-2-induced ectopic bone formation. Sci Rep. 2020;10:4751.
doi: 10.1038/s41598-020-61825-2
Coomes AM, Mealey BL, Huynh-Ba G, Barboza-Arguello C, Moore WS, Cochran DL. Buccal bone formation after flapless extraction: a randomized, controlled clinical trial comparing recombinant human bone morphogenetic protein 2/absorbable collagen carrier and collagen sponge alone. J Periodontol. 2014;85:525–35.
doi: 10.1902/jop.2013.130207
Neovius E, Lemberger M, Docherty Skogh AC, Hilborn J, Engstrand T. Alveolar bone healing accompanied by severe swelling in cleft children treated with bone morphogenetic protein-2 delivered by hydrogel. J Plast Reconstr Aesthet Surg. 2013;66:37–42.
doi: 10.1016/j.bjps.2012.08.015
Tian H, Zhou T, Chen H, Li C, Jiang Z, Lao L, et al. Bone morphogenetic protein-2 promotes osteosarcoma growth by promoting epithelial-mesenchymal transition (EMT) through the Wnt/β-catenin signaling pathway. J Orthop Res. 2019;37:1638–48.
doi: 10.1002/jor.24244
Liu Y, de Groot K, Hunziker EB. BMP-2 liberated from biomimetic implant coatings induces and sustains direct ossification in an ectopic rat model. Bone. 2005;36:745–57.
doi: 10.1016/j.bone.2005.02.005
Gundersen HJ, Jensen EB. The efficiency of systematic sampling in stereology and its prediction. J Microsc. 1987;147:229–63.
doi: 10.1111/j.1365-2818.1987.tb02837.x
Wu G, Liu Y, Iizuka T, Hunziker EB. The effect of a slow mode of BMP-2 delivery on the inflammatory response provoked by bone-defect-filling polymeric scaffolds. Biomaterials. 2010;31:7485–93.
doi: 10.1016/j.biomaterials.2010.06.037
Cruz-Orive LM, Weibel ER. Recent stereological methods for cell biology: a brief survey. Am J Physiol. 1990;258:L148–56.
Gretzer C, Emanuelsson L, Liljensten E, Thomsen P. The inflammatory cell influx and cytokines changes during transition from acute inflammation to fibrous repair around implanted materials. J Biomater Sci Polym Ed. 2006;17:669–87.
doi: 10.1163/156856206777346340
McNally AK, Anderson JM. Macrophage fusion and multinucleated giant cells of inflammation. Adv Exp Med Biol. 2011;713:97–111.
doi: 10.1007/978-94-007-0763-4_7
Lin X, Hunziker EB, Liu T, Hu Q, Liu Y. Enhanced biocompatibility and improved osteogenesis of coralline hydroxyapatite modified by bone morphogenetic protein 2 incorporated into a biomimetic coating. Mater Sci Eng C Mater Biol Appl. 2019;96:329–36.
doi: 10.1016/j.msec.2018.11.017
Wei L, Yu D, Wang M, Deng L, Wu G, Liu Y. Dose effects of slow-released bone morphogenetic protein-2 functionalized beta-tricalcium phosphate in repairing critical-sized bone defects. Tissue Eng Part A. 2020;26:120–9.
doi: 10.1089/ten.tea.2019.0161
Wu G, Hunziker EB, Zheng Y, Wismeijer D, Liu Y. Functionalization of deproteinized bovine bone with a coating-incorporated depot of BMP-2 renders the material efficiently osteoinductive and suppresses foreign-body reactivity. Bone. 2011;49:1323–30.
doi: 10.1016/j.bone.2011.09.046
Tsai AT, Rice J, Scatena M, Liaw L, Ratner BD, Giachelli CM. The role of osteopontin in foreign body giant cell formation. Biomaterials. 2005;26:5835–43.
doi: 10.1016/j.biomaterials.2005.03.003
Wei F, Zhou Y, Wang J, Liu C, Xiao Y. The immunomodulatory role of BMP-2 on macrophages to accelerate osteogenesis. Tissue Eng Part A. 2018;24:584–94.
doi: 10.1089/ten.tea.2017.0232
Chen Z, Wu C, Gu W, Klein T, Crawford R, Xiao Y. Osteogenic differentiation of bone marrow MSCs by beta-tricalcium phosphate stimulating macrophages via BMP2 signalling pathway. Biomaterials. 2014;35:1507–18.
doi: 10.1016/j.biomaterials.2013.11.014
Lu J, Descamps M, Dejou J, Koubi G, Hardouin P, Lemaitre J, et al. The biodegradation mechanism of calcium phosphate biomaterials in bone. J Biomed Mater Res. 2002;63:408–12.
doi: 10.1002/jbm.10259
Lee HR, Lee DH, Seok SY, Kim IH, Cho JH, Hwang CJ. Meta-analysis on efficacy and complications of bone morphogenetic protein-2 for posterior fusion of cervical spine. World Neurosurg. 2024;183:e3–10.
doi: 10.1016/j.wneu.2023.09.035
Zara JN, Siu RK, Zhang X, Shen J, Ngo R, Lee M, et al. High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo. Tissue Eng Part A. 2011;17:1389–99.
doi: 10.1089/ten.tea.2010.0555
Lee KB, Taghavi CE, Song KJ, Sintuu C, Yoo JH, Keorochana G, et al. Inflammatory characteristics of rhBMP-2 in vitro and in an in vivo rodent model. Spine (Phila Pa 1976). 2011;36:E149–54.
doi: 10.1097/BRS.0b013e3181f2d1ec