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Journal articles on the topic 'Rhbmp2'

Author: Grafiati

Published: 8 July 2023

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1

Colange, Ana Lucia, Carlos Sabino de Oliveira, Benedito Domingos Neto, Heloisa Sobreiro Selistre de Araújo, Eliane Trovatti, and Monica Rosas da Costa Iemma. "Effect on viability and cellular proliferation of rhBMP-2 immobilized on TEMPO modified cellulose hydrogel." Research, Society and Development 11, no. 11 (August 29, 2022): e471111133260. http://dx.doi.org/10.33448/rsd-v11i11.33260.

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BMP´s are signaling proteins that belong to the Transforming Growth Factor-β (TGF-β) superfamily. These proteins promote the recruitment and differentiation of mesenchymal progenitor cells into bone forming cells, the osteoblasts and increase the rate of bone formation. The carrier systems to release rhBMP-2 to the action site are based on the use of free and soluble BMP incorporated into biopolymers such as collagen, gelatin, chitosan, hyaluronic acid and silk. The fused rhBMP-2-thioredoxin could be an interesting approach for new advances in the field of carrying systems of these growth factors. The fused protein thioredoxin can be useful as a coupling agent of BMP-2 to the carrier system, binding it to the surface of the matrix and it is one of the main aims of this work. The recombinant protein rhBMP-2 was produced by IPTG induction obtaining a soluble protein without the need for refolding process. The immobilization of rhBMP-2 at the surface of the TEMPO modified cellulose nanofibrils was indicated by FTIR spectroscopy. The cellular viability tests indicated increased proliferative behavior of both, C2C12 and stem cells from rats, when seeded in presence of rhBMP2 when compared to the free rhBMP2 substrate. The calcified extracellular matrix confirmed the increased activity of the rhBMP2-cellulose substrate, indicating the success of the proposed method. The cell proliferation assays indicated the method used to immobilize rhBMP2 onto the surface of the TEMPO modified cellulose was successful. The cells growth increased when compared to the reference sample free of rhBMP2.

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Jeong, Byung-Chul, Hyuck Choi, Sung-Woong Hur, Jung-Woo Kim, Sin-Hye Oh, Hyun-Seung Kim, Soo-Chang Song, Keun-Bae Lee, Kwang-Bum Park, and Jeong-Tae Koh. "Repair of Cranial Bone Defects Using rhBMP2 and Submicron Particle of Biphasic Calcium Phosphate Ceramics with Through-Hole." BioMed Research International 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/926291.

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Recently a submicron particle of biphasic calcium phosphate ceramic (BCP) with through-hole (donut-shaped BCP (d-BCP)) was developed for improving the osteoconductivity. This study was performed to examine the usefulness of d-BCP for the delivery of osteoinductive rhBMP2 and the effectiveness on cranial bone regeneration. The d-BCP was soaked in rhBMP2 solution and then freeze-dried. Scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), and Raman spectroscopy analyses confirmed that rhBMP2 was well delivered onto the d-BCP surface and the through-hole. The bioactivity of the rhBMP2/d-BCP composite was validated in MC3T3-E1 cells as anin vitromodel and in critical-sized cranial defects in C57BL/6 mice. When freeze-dried d-BCPs with rhBMP2 were placed in transwell inserts and suspended above MC3T3-E1, alkaline phosphatase activity and osteoblast-specific gene expression were increased compared to non-rhBMP2-containing d-BCPs. For evaluatingin vivoeffectiveness, freeze-dried d-BCPs with or without rhBMP2 were implanted into critical-sized cranial defects. Microcomputed tomography and histologic analysis showed that rhBMP2-containing d-BCPs significantly enhanced cranial bone regeneration compared to non-rhBMP2-containing control. These results suggest that a combination of d-BCP and rhBMP2 can accelerate bone regeneration, and this could be used to develop therapeutic strategies in hard tissue healing.

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Alobaidaan, Raed, Jeremiah R. Cohen, Elizabeth L. Lord, Zorica Buser, S. Tim Yoon, Jim A. Youssef, Jong-Beom Park, Darrel S. Brodke, Jeffrey C. Wang, and Hans-Joerg Meisel. "Complication Rates in Posterior Lumbar Interbody Fusion (PLIF) Surgery With Human Bone Morphogenetic Protein 2: Medicare Population." Global Spine Journal 7, no. 8 (May 16, 2017): 770–73. http://dx.doi.org/10.1177/2192568217696695.

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Study Design: Retrospective cohort study among Medicare beneficiaries who underwent posterior lumbar interbody fusion (PLIF) surgery. Objective: To identify the complication rates associated with the use of bone morphogenetic protein 2 (BMP2) in PLIF. Human BMP2 is commonly used in the “off-label” manner for various types of spine fusion procedures, including PLIF. However, recent studies have reported potential complications associated with the recombinant human BMP2 (rhBMP2) use in the posterior approach. Methods: Medicare records within the PearlDiver database were queried for patients undergoing PLIF procedure with and without rhBMP2 between 2005 and 2010. We evaluated complications within 1 year postoperatively. Chi-square was used to compare the complication rates between the 2 groups. Results: A total of 8609 patients underwent PLIF procedure with or without rhBMP2. Individual complication rates in the rhBMP2 group ranged from 0.45% to 7.68% compared with 0.65% to 10.99 in the non-rhBMP2 group. Complication rates for cardiac, pulmonary, lumbosacral neuritis, infection, wound, and urinary tract (include acute kidney failure and post-operative complications) were significantly lower in the rhBMP2 group ( P < .05). There was no difference in the rates of central nervous system complications or radiculitis between the 2 groups. Conclusion: Our data showed that the patients who received rhBMP2 had lower complication rates compared to the non-rhBMP2 group. However, use of rhBMP2 was associated with a higher rate of pseudarthrosis. We did not observe any difference in radiculitis and central nervous system complications between the groups.

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Por, Yong-Chen, Carlos Raul Barceló, Kenneth E. Salyer, David G. Genecov, Karen Troxel, El Gendler, Mohammed E. Elsalanty, and Lynne A. Opperman. "Bone Generation in the Reconstruction of a Critical Size Calvarial Defect in an Experimental Model†." Annals of the Academy of Medicine, Singapore 36, no. 11 (November 15, 2007): 911–19. http://dx.doi.org/10.47102/annals-acadmedsg.v36n11p911.

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Objective: This study was designed to investigate the optimal combination of known osteogenic biomaterials with shape conforming struts to achieve calvarial vault reconstruction, using a canine model. Methods: Eighteen adolescent beagles were divided equally into 6 groups. A critical size defect of 6 x 2 cm traversed the sagittal suture. The biomaterials used for calvarial reconstruction were demineralised perforated bone matrix (DBM), recombinant human bone morphogenetic protein-2 (rhBMP2) and autogenous platelet-rich plasma (PRP). The struts used were cobalt chrome (metal) or resorbable plate. The groupings were as follows: 1) DBM + metal, 2) DBM + PRP + metal, 3) DBM + PRP + resorbable plate, 4) DBM + rhBMP2 + metal, 5) DBM + rhBMP2 + PRP + metal, and 6) DBM + rhBMP2 + resorbable plate. Animals were euthanised at 3 months post-surgery. There was no mortality or major complications. Analysis was performed macroscopically, histologically, and with computed tomography (CT). Results: There was complete bony regeneration in the rhBMP2 groups only. Non-rhBMP2 groups had minimal bony ingrowth from the defect edges and on the dural surface, a finding confirmed by CT scan and histology. PRP did not enhance bone regeneration. Shape conformation was good with both metal and resorbable plate. Conclusion: rhBMP2 but not PRP accelerated calvarial regeneration in 3 months. The DBM in the rhBMP2 groups were substituted by new trabecular bone. Shape molding was good with both metal and resorbable plate. Key words: Critical size calvarial defect, Cranial vault reconstruction, Metal struts, Resorbable plates, rhBMP2

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Patel, Harshadkumar A., Ian J. Wellington, Klair Lubonja, John W. Stelzer, Christopher L. Antonacci, Ergin Coskun, Mark P. Cote, Hardeep Singh, Scott S. Mallozzi, and Isaac L. Moss. "Current Trends in Recombinant Human Bone Morphogenetic Protein 2 (rhBMP2) Usage for Spinal Fusion Surgery." Medicina 59, no. 5 (May 3, 2023): 878. http://dx.doi.org/10.3390/medicina59050878.

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(1) Background: Since first approved by the FDA, on-label and off-label usage of recombinant human bone morphogenetic protein 2 (rhBMP2) for spinal fusion surgeries has become widespread. While many studies have investigated the safety and efficacy of its use, as well as its economic impact, few have looked at the current trends in its on- and off-label use. The goal of this study is to evaluate the current trends of on- and off-label rhBMP2 use for spinal fusion surgery. (2) Methods: A deidentified survey was created and electronically distributed to members of two international spine societies. Surgeons were asked to report their demographic information, surgical experience, and current usage of rhBMP2. They were then presented with five spinal fusion procedures and asked to report if they use rhBMP2 for these indications in their current practice. Responses were stratified between rhBMP2 users vs. non-users and on-label vs. off-label use. Data were analyzed using chi-square with Fisher’s exact test for categorical data. (3) Results: A total of 146 respondents completed the survey with a response rate of 20.5%. There was no difference in overall rhBMP2 usage based on specialty, experience, or number of cases per year. Fellowship-trained surgeons and those who practice in the United States were more likely to use rhBMP2. Surgeons who were trained in the Southeast and Midwest regions reported the highest usage rates. rhBMP2 use was more common among fellowship-trained and US surgeons for ALIFs; non-US surgeons for multilevel anterior cervical discectomy and fusions; and fellowship-trained and orthopedic spine surgeons for lateral lumbar interbody fusions. Non-US surgeons were more likely to use rhBMP2 for off-label indications compared to surgeons from the US. (4) Conclusions: While various demographics of surgeons report different rates of rhBMP2 use, off-label use remains relatively commonplace amongst practicing spine surgeons.

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Fujioka-Kobayashi, Masako, Mustafa Abd El Raouf, Nikola Saulacic, Eizaburo Kobayashi, Yufeng Zhang, Benoit Schaller, and Richard J. Miron. "Superior bone-inducing potential of rhBMP9 compared to rhBMP2." Journal of Biomedical Materials Research Part A 106, no. 6 (February 19, 2018): 1561–74. http://dx.doi.org/10.1002/jbm.a.36359.

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Fujioka‐Kobayashi, Masako, Mustafa Abd El Raouf, Nikola Saulacic, Eizaburo Kobayashi, Yufeng Zhang, Benoit Schaller, and Richard J. Miron. "Superior bone‐inducing potential of rhBMP9 compared to rhBMP2." Journal of Biomedical Materials Research Part A 107, no. 6 (May 3, 2019): 1351. http://dx.doi.org/10.1002/jbm.a.36591.

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8

Zhao, He, Yali Ma, Dahui Sun, Wendi Ma, Jihang Yao, and Mei Zhang. "Preparation and Characterization of Coaxial Electrospinning rhBMP2-Loaded Nanofiber Membranes." Journal of Nanomaterials 2019 (August 29, 2019): 1–13. http://dx.doi.org/10.1155/2019/8106985.

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DEX and rhBMP2-loaded core-shell nanofiber membranes were synthesized by electrospinning method in one step. Zein/PLLA, Zein-DEX/PLLA, Zein/PLLA-rhBMP2, and Zein-DEX/PLLA-rhBMP2 were fabricated; and morphology, hydrophilicity, mechanics properties, in vitro drug release behavior, cell proliferation, and osteogenic differentiation were investigated. The results showed that the dual-release system containing rhBMP2 and DEX prepared by electrospinning had rough surface, constant drug release behavior, and could also significantly promote cell proliferation and osteogenic differentiation of RMSCs, indicating that the scaffolds we fabricated might be suitable for bone tissue engineering.

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Lao, Lifeng, Jeremiah R. Cohen, Zorica Buser, Darrel S. Brodke, S. Tim Yoon, Jim A. Youssef, Jong-Beom Park, Hans-Joerg Meisel, and Jeffrey C. Wang. "Trends Analysis of rhBMP2 Utilization in Single-Level Anterior Lumbar Interbody Fusion in the United States." Global Spine Journal 8, no. 2 (May 16, 2017): 137–41. http://dx.doi.org/10.1177/2192568217701119.

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Study Design: Retrospective case study. Objective: To evaluate the trends and demographics of recombinant human bone morphogenetic protein 2 (rhBMP2) utilization in single-level anterior lumbar interbody fusion (ALIF) in the United States. Methods: Patients who underwent single-level ALIF from 2005 to 2011 were identified by searching ICD-9 diagnosis and procedure codes in the PearlDiver Patient Records Database (PearlDiver Technologies, Fort Wayne, IN), a national database of orthopedic insurance records. The year of procedure, age, gender, and region of the United States were analyzed for each patient. Results: A total of 921 patients were identified who underwent a single-level ALIF in this study. The average rate of single-level ALIF with rhBMP2 utilization increased (35%-48%) from 2005 to 2009, but sharply decreased to 16.7% in 2010 and 15.0% in 2011. The overall incidence of single-level ALIF without rhBMP2 (0.20 cases per 100 000 patients) was more than twice of the incidence of single-level ALIF with rhBMP2 (0.09 cases per 100 000 patients). The average rate of single-level ALIF with rhBMP2 utilization is highest in West (41.4%), followed by Midwest (33.3%), South (26.5%) and Northeast (22.2%). The highest incidence of single-level ALIF with rhBMP2 was observed in the group aged less than 65 years (compared with any other age groups, P < .001), with an incidence of 0.21 per 100 000 patients. Conclusions: The incidence of rhBMP2 utilization in single-level ALIF increased from 2006 to 2009, but decreased in 2010 and 2011. The Northeast region had the lowest incidence of rhBMP2 utilization. The group aged less than 65 years trended to have the higher incidence of single-level ALIF with rhBMP2 utilization.

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Esmail, Nabil, Zorica Buser, Jeremiah R. Cohen, Darrel S. Brodke, Hans-Joerg Meisel, Jong-Beom Park, Jim A. Youssef, Jeffrey C. Wang, and S. Tim Yoon. "Postoperative Complications Associated With rhBMP2 Use in Posterior/Posterolateral Lumbar Fusion." Global Spine Journal 8, no. 2 (April 20, 2017): 142–48. http://dx.doi.org/10.1177/2192568217698141.

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Study Design: Retrospective database review. Objective: Posterior/posterolateral lumbar fusion (PLF) is an effective treatment for a variety of spinal disorders; however, variations in surgical technique have different complication profiles. The aim of our study was to quantify the frequency of various complications in patients undergoing PLF with and without human recombinant bone morphogenetic protein 2 (rhBMP2). Methods: We queried the orthopedic subset of the Medicare database (PearlDiver) between 2005 and 2011 for patients undergoing PLF procedures with and without rhBMP2. Complication and reoperation rates were analyzed within 1 year of the index procedure. Complications assessed include: acute renal failure, deep vein thrombosis, dural tear, hematoma, heterotopic ossification, incision and drainage, cardiac complications, nervous system complications, osteolysis, pneumonia, pseudarthrosis, pulmonary embolism, radiculopathy, respiratory complications, sepsis, urinary retention, urinary tract infection, mechanical, and wound complications. Chi-square analysis was used to calculate the complication differences between the groups. Results: Our data revealed higher overall complication rates in patients undergoing PLF with rhBMP2 versus no_rhBMP2 (76.9% vs 68.8%, P < .05). Stratified by gender, rhBMP2 males had higher rates of mechanical complications, pseudarthrosis, and reoperations compared with no_rhBMP2 males ( P < .05), whereas rhBMP2 females had higher rates of pseudarthrosis, urinary tract infection, and urinary retention compared with no_rhBMP2 females ( P < .05). Conclusion: Our data revealed higher overall complication rates in PLF patients given rhBMP2 compared with no_rhBMP2. Furthermore, our data suggests that rhBMP2-associated complications may be gender specific.

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Yao, Jihang, Yilong Wang, Wendi Ma, Wenying Dong, Mei Zhang, and Dahui Sun. "Dual-Drug-Loaded Silk Fibroin/PLGA Scaffolds for Potential Bone Regeneration Applications." Journal of Nanomaterials 2019 (July 16, 2019): 1–16. http://dx.doi.org/10.1155/2019/8050413.

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Developing scaffold materials with excellent biocompatibility, mechanical properties, and controlled drug release properties is vital to tissue engineering. In this study, we fabricated silk fibroin (SF)/poly(lactide-co-glycolide) (PLGA) nanofiber scaffolds containing recombinant human bone morphogenetic protein 2 (rhBMP2) and dexamethasone (DXM) via coaxial electrospinning, which were used in in vitro bone formation with rat bone marrow mesenchymal stem cells (rBMSCs). An in vitro drug release study was adopted to evaluate the sustained release potential of the core-shell structured nanofibers. Furthermore, we detected the potential of the SF/PLGA nanofiber membrane in vitro. In vitro studies showed that rhBMP2 still remained active on the nanofiber membrane. In addition, the dual-drug-loaded nanofiber membrane showed an early burst release of DXM and late sustained release of rhBMP2. rhBMP2 and DXM exhibited strong osteogenic differentiation potential when they acted on rBMSCs. Therefore, the SF/PLGA nanofiber membrane loaded with rhBMP2 and DXM has great potential for the enhancement of bone regeneration.

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Hanif, Muhammad Umair, Roquyya Gul, Muhammad Imran Hanif, and Abid Ali Hashmi. "Heterologous Secretory Expression and Characterization of Dimerized Bone Morphogenetic Protein 2 inBacillus subtilis." BioMed Research International 2017 (2017): 1–11. http://dx.doi.org/10.1155/2017/9350537.

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Recombinant human Bone Morphogenetic Protein 2 (rhBMP2) has important applications in the spine fusion and ortho/maxillofacial surgeries. Here we first report the secretory expression of biological active dimerized rhBMP2 fromBacillus subtilissystem. The mature domain of BMP2 gene was amplified from pTz57R/BMP2 plasmid. By using pHT43 expression vector two constructs, pHT43-BMP2-M (single BMP2 gene) and pHT43-BMP2-D (two BMP2 genes coupled with a linker to produce a dimer), were designed. After primary cloning (DH5αstrain) and sequence analysis, constructs were transformed intoBacillus subtilisfor secretory expression. Expression conditions like media (2xYT) and temperature (30°C) were optimized. Maximum 35% and 25% secretory expression of monomer (~13 kDa) and dimer (~25 kDa), respectively, were observed on SDS-PAGE in SCK6 strain. The expression and dimeric nature of rhBMP2 were confirmed by western blot and native PAGE analysis. For rhBMP2 purification, 200 ml culture supernatant was freeze dried to 10 ml and dialyzed (Tris-Cl, pH 8.5) and Fast Protein Liquid Chromatography (6 ml, Resource Q column) was performed. The rhBMP2 monomer and dimer were eluted at 0.9 M and 0.6 M NaCl, respectively. The alkaline phosphatase assay of rhBMP2 (0, 50, 100, 200, and 400 ng/ml) was analyzed on C2C12 cells and maximum 200 ng/ml activity was observed in dose dependent manner.

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Zheng, Yuanna, Gang Wu, Juan Zhao, Linhong Wang, Ping Sun, and Zhiyuan Gu. "rhBMP2/7 Heterodimer: An Osteoblastogenesis Inducer of Not Higher Potency but Lower Effective Concentration Compared with rhBMP2 and rhBMP7 Homodimers." Tissue Engineering Part A 16, no. 3 (March 2010): 879–87. http://dx.doi.org/10.1089/ten.tea.2009.0312.

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Behrens, Christina, Philipp Kauffmann, Nikolaus von Hahn, Uwe Schirmer, Klaus Liefeith, and Henning Schliephake. "Collagen-Based Osteogenic Nanocoating of Microrough Titanium Surfaces." International Journal of Molecular Sciences 23, no. 14 (July 15, 2022): 7803. http://dx.doi.org/10.3390/ijms23147803.

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The aim of the present study was to develop a collagen/heparin-based multilayer coating on titanium surfaces for retarded release of recombinant human bone morphogenic protein 2 (rhBMP2) to enhance the osteogenic activity of implant surfaces. Polyelectrolyte multilayer (PEM) coatings were constructed on sandblasted/acid-etched surfaces of titanium discs using heparin and collagen. PEM films of ten double layers were produced and overlayed with 200 µL of a rhBMP2 solution containing 15 µg rhBMP2. Subsequently, cross-linking of heparin molecules was performed using EDC/NHS chemistry to immobilize the incorporated rhBMP2. Release characteristics for 3 weeks, induction of Alkaline Phosphatase (ALP) in C2C12 cells and proliferation of human mesenchymal stem cells (hMSCs) were evaluated to analyze the osteogenic capacity of the surface. The coating incorporated 10.5 µg rhBMP2 on average per disc and did not change the surface morphology. The release profile showed a delivery of 14.5% of the incorporated growth factor during the first 24 h with a decline towards the end of the observation period with a total release of 31.3%. Cross-linking reduced the release with an almost complete suppression at 100% cross-linking. Alkaline Phosphatase was significantly increased on day 1 and day 21, indicating that the growth factor bound in the coating remains active and available after 3 weeks. Proliferation of hMSCs was significantly enhanced by the non-cross-linked PEM coating. Nanocoating using collagen/heparin-based PEMs can incorporate clinically relevant amounts of rhBMP2 on titanium surfaces with a retarded release and a sustained enhancement of osteogenic activity without changing the surface morphology.

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Jiang, Ying, Weihao Li, and Congyun Bao. "A Novel Glucose-Sensitive Scaffold Accelerates Osteogenesis in Diabetic Conditions." BioMed Research International 2022 (March 18, 2022): 1–10. http://dx.doi.org/10.1155/2022/4133562.

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Mandibular bone regeneration is still a big challenge in those diabetic patients with poorly controlled blood glucose. In this study, we prepared a novel glucose-sensitive controlled-release fiber scaffold (PVA-HTCC/PEO-rhBMP2-glucose oxidase (PHPB-G)), which contained the recombinant human bone morphogenetic protein 2 (rhBMP2) by coaxial cospinning and grafted with glucose oxidase (GOD). We presented evidence that PHPB-G could undergo a series of structural changes with the blood glucose and promoted bone regeneration in diabetic rat. PHPB-G expanded the voids in nanofibers when blood glucose levels elevated. More importantly, its slow-release rhBMP2 effectively promoted the healing of bone defects. These data suggested that the PHPB-G delivery system may provide a potential treatment strategy for patients with severe diabetic alveolar bone defects.

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Maia-Pinto, Marianna O. C., Ana Carolina B. Brochado, Bruna Nunes Teixeira, Suelen C. Sartoretto, Marcelo J. Uzeda, Adriana T. N. N. Alves, Gutemberg G. Alves, Mônica D. Calasans-Maia, and Rossana M. S. M. Thiré. "Biomimetic Mineralization on 3D Printed PLA Scaffolds: On the Response of Human Primary Osteoblasts Spheroids and In Vivo Implantation." Polymers 13, no. 1 (December 27, 2020): 74. http://dx.doi.org/10.3390/polym13010074.

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This study aimed to assess the response of 3D printed polylactic acid (PLA) scaffolds biomimetically coated with apatite on human primary osteoblast (HOb) spheroids and evaluate the biological response to its association with Bone Morphogenetic Protein 2 (rhBMP-2) in rat calvaria. PLA scaffolds were produced via 3D printing, soaked in simulated body fluid (SBF) solution to promote apatite deposition, and characterized by physical-chemical, morphological, and mechanical properties. PLA-CaP scaffolds with interconnected porous and mechanical properties suitable for bone repairing were produced with reproducibility. The in vitro biological response was assessed with human primary osteoblast spheroids. Increased cell adhesion and the rise of in vitro release of growth factors (Platelet-Derived Growth Factor (PDGF), Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF) was observed for PLA-CaP scaffolds, when pre-treated with fetal bovine serum (FBS). This pre-treatment with FBS was done in a way to enhance the adsorption of serum proteins, increasing the number of bioactive sites on the surface of scaffolds, and to partially mimic in vivo interactions. The in vivo analysis was conducted through the implantation of 3D printed PLA scaffolds either alone, coated with apatite (PLA-CaP) or PLA-CaP loaded with rhBMP-2 on critical-sized defects (8 mm) of rat calvaria. PLA-CaP+rhBMP2 presented higher values of newly formed bone (NFB) than other groups at all in vivo experimental periods (p < 0.05), attaining 44.85% of NFB after six months. These findings indicated two new potential candidates as alternatives to autogenous bone grafts for long-term treatment: (i) 3D-printed PLA-CaP scaffold associated with spheroids, since it can reduce the time of repair in situ by expression of biomolecules and growth factors; and (ii) 3D-printed PLA-CaP functionalized rhBMP2 scaffold, a biocompatible, bioactive biomaterial, with osteoconductivity and osteoinductivity.

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Lian, Huan, Han Wang, Qianqian Han, and Chunren Wang. "Quantification of rhBMP2 in bioactive bone materials." Regenerative Biomaterials 7, no. 1 (December 16, 2019): 71–75. http://dx.doi.org/10.1093/rb/rbz038.

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Abstract Bone morphogenetic protein (BMP), belongs to transforming growth factor-β (TGF-β) superfamily except BMP-1. Implanting BMP into muscular tissues induces ectopic bone formation at the site of implantation, which provides opportunity for the treatment of bone defects. Recombinant human BMP-2 (rhBMP-2) has been used clinically, but the lack of standard methods for quantifying rhBMP-2 biological activity greatly hindered the progress of commercialization. In this article, we describe an in vitro rhBMP-2 quantification method, as well as the data analyzation pipeline through logistic regression in RStudio. Previous studies indicated that alkaline phosphatase (ALP) activity of C2C12 cells was significantly increased when exposed to rhBMP-2, and showed dose-dependent effects in a certain concentration range of rhBMP-2. Thus, we chose to quantify ALP activity as an indicator of rhBMP-2 bioactivity in vitro. A sigmoid relationship between the ALP activity and concentration of rhBMP-2 was discovered. However, there are tons of regression models for such a non-linear relationship. It has always been a major concern for researchers to choose a proper model that not only fit data accurately, but also have parameters representing practical meanings. Therefore, to fit our rhBMP-2 quantification data, we applied two logistic regression models, three-parameter log-logistic model and four-parameter log-logistic model. The four-parameter log-logistic model (adj-R2 > 0.98) fits better than three-parameter log-logistic model (adj-R2 > 0.75) for the sigmoid curves. Overall, our results indicate rhBMP-2 quantification in vitro can be accomplished by detecting ALP activity and fitting four-parameter log-logistic model. Furthermore, we also provide a highly adaptable R script for any additional logistic models.

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Baskin, Jonathan Zvi, Alvin Ko, and Steven Eppell. "rhBMP2 Release Profiles in Collagen-Apatite Composites." Otolaryngology–Head and Neck Surgery 141, no. 2_suppl (September 2009): P40. http://dx.doi.org/10.1016/j.otohns.2009.06.115.

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Fujioka-Kobayashi, Masako, Kosaku Sawada, Eizaburo Kobayashi, Benoit Schaller, Yufeng Zhang, and Richard J. Miron. "Osteogenic potential of rhBMP9 combined with a bovine-derived natural bone mineral scaffold compared to rhBMP2." Clinical Oral Implants Research 28, no. 4 (March 14, 2016): 381–87. http://dx.doi.org/10.1111/clr.12804.

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Cicciù, M., A. S. Herford, E. Stoffella, G. Cervino, and D. Cicciù. "Protein-Signaled Guided Bone Regeneration Using Titanium Mesh and Rh-BMP2 in Oral Surgery: A Case Report Involving Left Mandibular Reconstruction after Tumor Resection." Open Dentistry Journal 6, no. 1 (March 9, 2012): 51–55. http://dx.doi.org/10.2174/1874210601206010051.

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Recombinant human bone morphogenetic protein-2 (rhBMP-2) is an osteoinductive protein approved for use in oral and maxillofacial defect reconstruction. Growth factors act as mediators of cellular growth on morphogenesis and mythogenesis phases. Utilized as recombinant proteins, these growth factors need the presence of local target cells capable of obtaining the required results. This cell population may be present at the wound site or added to scaffolding material before implantation at the surgical site. The aim of this study is to evaluate the clinical and radiographic results of a reported case with a large bone defect, treated with an absorbable collagen sponge, rhBMP-2 and a titanium plate and mesh. The Authors want to report a case which shows the resulting effectiveness of the rhBMP2 action regarding a large, mandibular defect reconstruction. This case also shows how the removal of a rare tumor such as a ghost cell tumor of the jaw may be treated without harvesting bone from another body site. A quick diagnosis of the lesions is important in order to perform the most suitable treatment. The Authors also underline the clinical and histological steps to insure the correct treatment is carried out to solve the case. Moreover, from results obtained from this case, it is possible to highlight several clinical benefits for the patient by adding rhBMP-2 to the common allograft to not only have alveolar reconstruction defects and sinus floor augmentation, but also to have alveolar cleft reconstruction and to treat segmental defects.

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Fujioka-Kobayashi, Masako, Kosaku Sawada, Eizaburo Kobayashi, Benoit Schaller, Yufeng Zhang, and Richard J. Miron. "Recombinant Human Bone Morphogenetic Protein 9 (rhBMP9) Induced Osteoblastic Behavior on a Collagen Membrane Compared With rhBMP2." Journal of Periodontology 87, no. 6 (June 2016): e101-e107. http://dx.doi.org/10.1902/jop.2016.150561.

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Saulacic, Nikola, Benoit Schaller, Fernando Muñoz, Masako Fujioka-Kobayashi, Eizaburo Kobayashi, Niklaus Lang, and Richard Miron. "RhBMP9 in comparison to rhBMP2 for ridge augmentation following tooth extraction - an experimental study in the Beagle dog." Clinical Oral Implants Research 29 (October 2018): 43. http://dx.doi.org/10.1111/clr.13356.

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Chang, Po-Chun, Bu-Yuan Liu, Cheng-Meei Liu, Hsin-Hua Chou, Ming-Hua Ho, Hwa-Chang Liu, Da-Ming Wang, and Lein-Tuan Hou. "Bone tissue engineering with novel rhBMP2-PLLA composite scaffolds." Journal of Biomedical Materials Research Part A 81A, no. 4 (2007): 771–80. http://dx.doi.org/10.1002/jbm.a.31031.

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Ivanjko, Natalia, Nikola Stokovic, Marina Milesevic, and Slobodan Vukicevic. "Comparison of efficacy of rhBMP2 and rhBMP6 delivered within autologous blood coagulum with synthetic ceramics in rat subcutaneous assay." Bone Reports 16 (May 2022): 101325. http://dx.doi.org/10.1016/j.bonr.2022.101325.

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Buser, Zorica, Darrel Brodke, Nabil Esmail, Hans-Joerg Meisel, Jong-Beom Park, Sue Lynn Myhre, Jim Youssef, Jeffrey C. Wang, and S. Tim Yoon. "Postoperative Complications Associated with rhBMP2 use in Posterior Lumbar Fusion." Global Spine Journal 6, no. 1_suppl (April 2016): s—0036–1582611—s—0036–1582611. http://dx.doi.org/10.1055/s-0036-1582611.

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Hou, Xiao-Fei, Dong-Wei Fan, Chui-Guo Sun, and Zhong-Qiang Chen. "Recombinant human bone morphogenetic protein-2–induced ossification of the ligamentum flavum in rats and the associated global modification of histone H3." Journal of Neurosurgery: Spine 21, no. 3 (September 2014): 334–41. http://dx.doi.org/10.3171/2014.4.spine13319.

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Object The primary object of this investigation was to study recombinant human bone morphogenetic protein–2 (rhBMP-2)–induced ossification of the ligamentum flavum and associated histone H3 modification in a rat model. In an additional set of studies the authors investigated spinal cord and behavioral changes in the same model. Methods The authors report on 2 separate sets of studies. A total of 90 rats were used for the 2 sets of studies (45 each); in each study, a lyophilized rhBMP-2 and collagen mixture (20 μg rhBMP-2 and 200 μl collagen) was implanted in the lumbar extradural space in 18 rats; another 18 animals were used for a sham-operation control group and underwent implantation of lyophilized collagen without rhBMP-2 at the same level; an additional 9 animals were used as untreated controls. Lumbar spinal samples were harvested from the rhBMP-2 groups and the shamoperation control groups at 1 week, 3 weeks, and 9 weeks after the operation. Samples were also obtained from untreated controls at the same time points. All samples were scanned using micro-CT and then made into paraffinembedded sections. The sections from the first set of 45 rats were stained using elastica van Gieson and toluidine blue, and the expression of histone modifications (H3K9ac, H3K18ac, H3K4me3, and H3K36me3) and osteogenic transcription factors (osterix, Runx2) was detected by immunohistochemistry. In the second set of studies, hindlimb motor function was assessed at 1 week, 3 weeks, and 9 weeks after surgery. After behavioral evaluation, samples were harvested, scanned using micro-CT, and then made into paraffin-embedded sections. The sections were stained using Luxol fast blue. The expression of NeuN was also detected using immunohistochemistry. Results Ossification was seen in the rhBMP-2 group from 1 week after insertion, and the volume of ossified mass increased at 3 and 9 weeks. There was no ossification seen in the sham-surgery and normal controls. The pathological changes of ossification involved ligament degeneration, cartilage formation, and, finally, bone replacement. Spinal cord evaluation showed a significant decrease in white matter content and number of neurons at 9 weeks after operation in the rhBMP-2–treated group (compared with findings in the sham-surgery and control groups as well as findings at the earlier time points in the rhBMP-2 group). Using immunohistochemical staining, histone modifications (H3K9ac, H3K18ac, H3K4me3, and H3K36me3) and osteogenic transcription factors (osterix, Runx2) all were found to be expressed in the fibrocartilage area of the rat ossified ligamentum flavum samples (rhBMP2 group). Conclusions This rhBMP-2–induced OLF is a typical endochondral ossification, which is similar to clinical OLF. The compressed spinal cord around the ossification site showed signs of a chronic degenerative process. Histone H3 modifications (H3K9ac, H3K18ac, H3K4me3, and H3K36me3) may play an important role in OLF.

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El-Ghannam, Ahmed. "Bioceramic Drug Delivery System for Cancer Treatment and Regenerative Medicine." Key Engineering Materials 696 (May 2016): 245–49. http://dx.doi.org/10.4028/www.scientific.net/kem.696.245.

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Silica-calcium-phosphate composite (SCPC) is a drug delivery platform that has successfully demonstrated the ability to bind and release several therapeutics including antibiotics, peptides, anticancer drugs, and growth factors. It has successfully demonstrated a unique capacity for bone regeneration. The present studies address the effect of the phosphate and silicate functional groups on drug binding and controlled release kinetics of Cisplatin (Cis). Moreover, the roles of ceramic composition and resorbability on rhBMP2 release kinetics and bone regeneration in a critical size calvarial defect in rabbit is presented.

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Saulacic, Nikola, Benoit Schaller, Fernando Muñoz, Masako Fujioka-Kobayashi, Eizaburo Kobayashi, Niklaus P. Lang, and Richard J. Miron. "Recombinant human BMP9 (RhBMP9) in comparison with rhBMP2 for ridge augmentation following tooth extraction: An experimental study in the Beagle dog." Clinical Oral Implants Research 29, no. 10 (October 2018): 1050–59. http://dx.doi.org/10.1111/clr.13371.

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Abarrategi, Ander, Ana Civantos, Viviana Ramos, José Vicente Sanz Casado, and José Luís López-Lacomba. "Chitosan Film as rhBMP2 Carrier: Delivery Properties for Bone Tissue Application." Biomacromolecules 9, no. 2 (February 2008): 711–18. http://dx.doi.org/10.1021/bm701049g.

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Tian, Zhichao, Yuanli Zhu, Jinjun Qiu, Hanfeng Guan, Liangyu Li, Shouchao Zheng, Xuehai Dong, and Jun Xiao. "Synthesis and characterization of UPPE-PLGA-rhBMP2 scaffolds for bone regeneration." Journal of Huazhong University of Science and Technology [Medical Sciences] 32, no. 4 (August 2012): 563–70. http://dx.doi.org/10.1007/s11596-012-0097-4.

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Balaji, S. M. "Use of rhBMP2 with bone grafts in pediatric jaw resection cases." International Journal of Oral and Maxillofacial Surgery 40, no. 10 (October 2011): 1096. http://dx.doi.org/10.1016/j.ijom.2011.07.236.

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Lohse, N., N. Moser, S. Backhaus, T. Annen, M. Epple, and H. Schliephake. "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 rats." Journal of Controlled Release 220 (December 2015): 201–9. http://dx.doi.org/10.1016/j.jconrel.2015.10.032.

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Lu, Daniel C., Luis M. Tumialán, and Dean Chou. "Multilevel anterior cervical discectomy and fusion with and without rhBMP-2: a comparison of dysphagia rates and outcomes in 150 patients." Journal of Neurosurgery: Spine 18, no. 1 (January 2013): 43–49. http://dx.doi.org/10.3171/2012.10.spine10231.

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Object Reported complications of recombinant human bone morphogenetic protein–2 (rhBMP-2) use in anterior cervical discectomy and fusion (ACDF) cases include dysphagia and cervical swelling. However, dysphagia often occurs after multilevel ACDF procedures performed with allograft (without BMP) as well. To date, there has been no large study comparing the dysphagia rates of patients who have undergone multilevel ACDF using allograft spacers with those who underwent ACDF using polyetheretherketone (PEEK) cages filled with rhBMP2. The authors report one of the first such comparisons between these 2 patient cohorts. Methods The authors retrospectively reviewed 150 patient records. Group 1 (BMP group) consisted of 100 patients who underwent multilevel ACDF with PEEK cages filled with rhBMP-2 and instrumented with a cervical plate. Group 2 (allograft group) included a matched control cohort of 50 patients who underwent multilevel ACDF with allograft spacers and anterior plate fixation (without rhBMP-2). Patient demographics were not significantly different between the groups. Fusion was assessed by means of dynamic radiographs and/or CT at routine intervals. Complications, dysphagia incidence, standardized dysphagia score, Nurick grades, and fusion rates were assessed. Results The mean follow-up for the BMP group (Group 1) was 35 months while the mean follow-up for the allograft group (Group 2) was 25 months. There was a complication rate of 13% in the BMP group compared with 8% in the allograft group (p < 0.005). There was no significant difference in overall dysphagia incidence between the BMP group and the allograft group (40% vs 44%, respectively; p > 0.05). However, there was a significant difference in the severity of dysphagia (using the SWAL-QOL dysphagia scoring system) between the 2 groups: 0.757 for the BMP group versus 0.596 for the allograft group (p < 0.005). In subgroup analysis, the use of rhBMP-2 significantly increased the severity of dysphagia in patients undergoing 2-level ACDF (p < 0.005). However, the severity of dysphagia did not differ significantly between groups when 3- or 4-level ACDF cases were compared. There was no pseudarthrosis in Group 1 (the BMP group) compared with a 16% pseudarthrosis rate in Group 2 (the allograft group) (p < 0.05). There was a weak correlation between the total rhBMP-2 dose and the dysphagia score (Kendall tau rank correlation coefficient 0.166, p = 0.046). Conclusions The use of rhBMP-2 in patients undergoing 2-level ACDF significantly increases the severity of dysphagia (dysphagia score) without affecting the overall incidence of dysphagia. However, there is no statistically significant difference in the incidence or severity of dysphagia between patients undergoing 3-level or 4-level ACDF treated with PEEK/rhBMP-2 and those treated with only allograft. The use of rhBMP-2 appears to reduce the risk of pseudarthrosis. This benefit is most pronounced in patients who undergo 4-level ACDF and are smokers.

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Durham, Emily L., Rajiv Kishinchand, Zachary J. Grey, and James J. Cray. "rhBMP2 alone does not induce macrophage polarization towards an increased inflammatory response." Molecular Immunology 117 (January 2020): 94–100. http://dx.doi.org/10.1016/j.molimm.2019.10.021.

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Lindley, Emily, Susan Estes, Evalina Burger, and Vikas Patel. "P82. Evaluation of rhBMP2 Fibrin Glue-associated Edema in Rabbit Muscle Tissue." Spine Journal 8, no. 5 (September 2008): 140S—141S. http://dx.doi.org/10.1016/j.spinee.2008.06.724.

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Preativatanyou, Kanok, and Sittisak Honsawek. "RhBMP-2 and -7 combined with absorbable collagen sponge carrier enhance ectopic bone formation: An in vivo bioassay." Asian Biomedicine 5, no. 1 (February 1, 2011): 85–92. http://dx.doi.org/10.5372/1905-7415.0501.010.

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Abstract Background: Recombinant human bone morphogenetic proteins (rhBMPs) have been characterized especially chondrogenic and osteogenic activity both in vitro and in vivo studies. However, delivery of more than one growth factor by sustained release carrier to orthopedic site has yet been questionable in terms of efficacy and synergism. Objective: Evaluate osteoinductivity and synergistic effect of rhBMP-2 and -7 using absorbable collagen sponge (ACS) carrier system in vivo. Methods: cDNA of BMP-2 and -7 active domains were cloned and expressed in Escherichia coli BL21 StarTM (DE3) using pRSETc expression system. Then, the purified rhBMPs were loaded onto ACS and evaluated by in vivo rat subcutaneous bioassay. Two and eight weeks postoperatively, all treated groups were histologically verified for evidence of new bone formation and neovascularization by hematoxylin-eosin staining and light microscopy. Results: The Wistar rat treated with rhBMP-2 or -7/ACS exhibited new bone formation, compared to ACS control. The group treated with ACS supplemented with both rhBMP-2 and -7 significantly showed the osteoid matrix very well-organized into trabeculae-like structure with significant blood vessel invasion. Conclusion: The osteogenic induction of rhBMPs was combined with ACS carrier in the in vivo bioassay. In addition, the combination of both two potent recombinant osteoinductive cytokines, rhBMP-2 and -7, with ACS carrier demonstrated synergistic effect and might be a more promising and effective choice for therapeutic applications.

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Ryu, Dalsung, Byung-Hak Yoon, Chang-Hyun Oh, Moon-Hang Kim, Ji-Yong Kim, Seung Hwan Yoon, and Senyon Choe. "Activin A/BMP2 Chimera (AB204) Exhibits Better Spinal Bone Fusion Properties than rhBMP2." Journal of Korean Neurosurgical Society 61, no. 6 (November 1, 2018): 669–79. http://dx.doi.org/10.3340/jkns.2017.0295.

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Schliephake, H., H. A. Weich, J. Schulz, and R. Gruber. "In vitro characterization of a slow release system of polylactic acid and rhBMP2." Journal of Biomedical Materials Research Part A 83A, no. 2 (2007): 455–62. http://dx.doi.org/10.1002/jbm.a.31227.

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Nguyen, Thi-Hiep, and Byong-Taek Lee. "In vitroandin vivostudies of rhBMP2-coated PS/PCL fibrous scaffolds for bone regeneration." Journal of Biomedical Materials Research Part A 101A, no. 3 (September 8, 2012): 797–808. http://dx.doi.org/10.1002/jbm.a.34382.

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Mukhametov, U. F., S. V. Lyulin, D. Yu Borzunov, and I. F. Gareev. "Evaluation of the potential immunogenicity of recombinant human bone morphogenetic proteins." Ural Medical Journal 21, no. 5 (November 5, 2022): 116–27. http://dx.doi.org/10.52420/2071-5943-2022-21-5-116-127.

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Introduction. Bone morphogenetic proteins (BMPs) are a subgroup of the transforming growth factor-β (TGF-β) superfamily where they play an important role in bone formation and repair. Recombinant human bone morphogenetic proteins (rhBMPs) are currently being clinically evaluated for their effectiveness in enhancing bone tissue regeneration processes after injuries and diseases of the musculoskeletal system. Clinical trials were accompanied by detailed safety assessments using both in vitro and in vivo assays. Concerns were initially raised about the immunogenicity of some therapeutic proteins due to their non-human origin. However, proteins derived from human serum or tissues and products derived from recombinant DNA, such as rhBMPs, identical or nearly identical to native human proteins, have also been shown to be immunogenic. The purpose. of this study is to review the potential immunogenicity of rhBMPs and compare the results of preclinical and clinical studies available to date between rhBMP-2 and rhBMP-7. Materials and methods. Using PubMed, Embase, the Cochrane Database, and Google Scholar, we conducted a comprehensive search for original papers, literature reviews, case reports, and meta-analyses demonstrating possible immune responses to rhBMPs. Results. This study analyzes possible reactions from the immune system when using rhBMPs in both clinical and preclinical studies. Antibody production has been found to be one of the side effects of rhBMPs. However, reported cases of immunogenicity of rhBMPs vary greatly due to the lack of standardization of methods. Conclusion. No immunologically related adverse events were observed in various clinical trials, and antibody formation never adversely affected new bone formation and clinical outcomes.

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Joseph, Vivek, and Yoga Raja Rampersaud. "Heterotopic Bone Formation With the Use of rhBMP2 in Posterior Minimal Access Interbody Fusion." Spine 32, no. 25 (December 2007): 2885–90. http://dx.doi.org/10.1097/brs.0b013e31815b7596.

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Berven, Sigurd, Stephen Ondra, Youjeong Kim, Jeffrey Toth, John Louis-Ugbo, and Maneesh Bawa. "43. A Direct Comparison of rhOP1 and rhBMP2 in a Rhesus Monkey Posterolateral Environment." Spine Journal 8, no. 5 (September 2008): 21S—22S. http://dx.doi.org/10.1016/j.spinee.2008.06.050.

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Herford, A. S., E. Stoffella, and M. Cicciù. "5 Years follow up of patient treated with rhBMP2 for large mandibulary bone defects." International Journal of Oral and Maxillofacial Surgery 40, no. 10 (October 2011): 1126. http://dx.doi.org/10.1016/j.ijom.2011.07.338.

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Mukhametov, U. F., S. V. Lyulin, D. Yu Borzunov, I. F. Gareev, O. A. Beylerli, and A. A. Sufianov. "Heterotopic ossification as a side effect of the use of recombinant human bone morphogenetic proteins." Genij Ortopedii 28, no. 1 (February 25, 2022): 123–32. http://dx.doi.org/10.18019/1028-4427-2022-28-1-123-132.

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Introduction Heterotopic ossification (HO), also known as myositis ossification, paraosteoarthropathy, or heterotopic calcification, among others, is a common pathological condition that refers to ectopic bone formation in soft tissues. Although the molecular mechanism of HO is not fully understood, it is believed that signaling of bone morphogenetic proteins (BMPs) plays a key role in the overall process of HO. Today, recombinant human BMP-2 (rhBMP-2) and recombinant human BMP-7 (rhBMP-7) have been already actively used in clinical practice in the treatment of bone defects. However, despite the positive sides of using rhBMPs, there are a number of side effects, one of which is HO. Purpose In this study, we demonstrate cases of HO following the use of rhBMPs in both clinical and preclinical studies and make an attempt to explain the relationship between the signaling pathways of BMPs and the HO process, as well as the possibilities of preventing and treating the HO process. Materials and methods PubMed, Embase, the Cochrane Database, and Google Scholar were comprehensively searched for original articles, literature reviews, case reports, and meta-analyses demonstrating a causal relationship between therapeutic rhBMPs and HO as a complication. Results This review analyzes the potential for therapeutic use of rhBMPs in neurosurgery and traumatology and orthopedics, demonstrated by both clinical and preclinical studies. In particular, the studies confirm that ectopic bone formation is one of the side effects following administration of rhBMPs. Moreover, the molecular mechanisms of the HO process were highlighted, and the possibilities of modern methods of prevention and treatment of HO were discussed. Conclusion According to the FDA safety database for rhBMPs, the rates of adverse effects related to HO range from 1 % to 10 %. However, to date, the clinical use of rhBMPs is justified, especially when there are no alternative substitutes for bone grafting.

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Wang, Jingxiao, Yuanna Zheng, Juan Zhao, Tie Liu, Lixia Gao, Zhiyuan Gu, and Gang Wu. "Low-dose rhBMP2/7 heterodimer to reconstruct peri-implant bone defects: a micro-CT evaluation." Journal of Clinical Periodontology 39, no. 1 (November 10, 2011): 98–105. http://dx.doi.org/10.1111/j.1600-051x.2011.01807.x.

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Hye Kim, Ji, Sa Ya Lee, Mi Seon Goh, Hun Jin Jeong, Young-Sam Cho, Seung-Jae Lee, and Jeong-Ho Yun. "The use of rhBMP2 loaded implant fixture and 3D-printed scaffold for vertical bone augmentation." Clinical Oral Implants Research 29 (October 2018): 107. http://dx.doi.org/10.1111/clr.2_13357.

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Yoon, Seung Hwan, JiYong Kim, and Chang Hyun Oh. "The Activin A/BMP 2 Chimera AB204 Exhibits Superior Spinal Bone Fusion Properties over rhBMP2." Spine Journal 15, no. 10 (October 2015): S88. http://dx.doi.org/10.1016/j.spinee.2015.07.016.

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Anand, Neel, John F. Hamilton, Brian Perri, Hamid Miraliakbar, and Theodore Goldstein. "Cantilever TLIF With Structural Allograft and RhBMP2 for Correction and Maintenance of Segmental Sagittal Lordosis." Spine 31, no. 20 (September 2006): E748—E753. http://dx.doi.org/10.1097/01.brs.0000240211.23617.ae.

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Hwang, Chang Ju, Alexander R. Vaccaro, James P. Lawrence, Joseph Hong, Huub Schellekens, Moulay Hicham Alaoui-Ismaili, and Dean Falb. "Immunogenicity of bone morphogenetic proteins." Journal of Neurosurgery: Spine 10, no. 5 (May 2009): 443–51. http://dx.doi.org/10.3171/2009.1.spine08473.

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Object The object of this paper is to review the immunogenicity of bone morphogenetic proteins (BMPs) and to compare the results of the immunogenicity characterization and clinical consequences between recombinant human (rh)BMP-2 and recombinant human osteogenic protein-1 (rhOP-1/BMP-7). Methods The immunogenicity of therapeutic proteins and its clinical effects were reviewed. The characteristics of BMPs were also described in terms of immunogenicity. The methods and results of antibody detection in various clinical trials of rhBMP-2 and rhOP-1 were compared, including the most recent studies using a systematic characterization strategy with both a binding assay and bioassay. Results Similar to all recombinant human proteins, rhBMPs induce immune responses in a select subgroup of patients. Adverse effects from this response in these patients, however, have not been reported with antibody formation to either rhBMP-2 or rhOP-1. Overall, the incidence of antibody formation was slightly higher in rhOP-1 trials than in rhBMP-2 trials. Conclusions Although they occur in a subgroup of patients, the immune responses against rhBMPs have no correlation with any clinical outcome or safety parameter. Clinicians, however, must be aware of the potential complications caused by the immunogenicity of BMPs until more studies clearly elucidate their safety.

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Kim, Sungwon, Cheonil Park, Byeong-Seok Moon, Hyoun-Ee Kim, and Tae-Sik Jang. "Enhancement of osseointegration by direct coating of rhBMP-2 on target-ion induced plasma sputtering treated SLA surface for dental application." Journal of Biomaterials Applications 31, no. 6 (November 23, 2016): 807–18. http://dx.doi.org/10.1177/0885328216679761.

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Owing to the excellent bioactive properties of recombinant human bone morphogenetic proteins (rhBMPs), dentistry considers them as a fascinating adjuvant alternative for enhancing bone regeneration and bone-to-implant junction in the early implantation stages. However, stable loading and delivery efficiency of rhBMPs on the implant surfaces involve major concerns because of the harsh wearing condition under load during implantation. In this study, to achieve successful rhBMP-2 delivery, a nanoporous surface structure is introduced on the sandblasting with large grit and acid-etching (SLA)-treated titanium (Ti) surface via the tantalum (Ta) target-ion induced plasma sputtering (TIPS) technique. Unlike oxidation-induced surface nanoporous fabrications on a Ti surface, TIPS-treated surfaces provide excellent structural unity of the nanoporous structure with the substrate due to their etching-based fabrication mechanism. SLA/TIPS-treated Ti exhibits distinct nanoporous structures on the microscale surface geometry and better hydrophilicity compared with SLA-treated Ti. A sufficiently empty nanoporous surface structure combined with the hydrophilic property of SLA/TIPS-treated Ti facilitates the formation of a thick and uniform coating layer of rhBMP-2 on the surface without any macro- and microcoagulation. Compared with the SLA-treated Ti surface, the amount of coated rhBMP-2 increases up to 63% on the SLA/TIPS-treated Ti surface. As a result, the in vitro pre-osteoblast cell response of the SLA/TIPS-treated Ti surface, especially cell adhesion and differentiation behaviors, improves remarkably. A bone-regenerating direct comparison between the rhBMP-2-coated SLA-treated and SLA/TIPS-treated Ti is conducted on a defective dog mandible model. After 8 weeks of implantation surgery, SLA/TIPS-treated Ti with rhBMP-2 exhibits a better degree of contact area for the implanted bone, which mineralizes new bones around the implant. Quantitative results of bone-in-contact ratio and new bone volume also show significantly higher values for the SLA/TIPS-treated Ti with the rhBMP-2 specimen. These results confirm that an SLA/TIPS-treated surface is a suitable rhBMP-2 carrier for a dental implant to achieve early and strong osseointegration of Ti dental implants.

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