RESUMEN
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is the predominant growth factor that effectively induces osteogenic differentiation in orthopedic procedures. However, the bioactivity and stability of rhBMP-2 are intrinsically associated with its sequence, structure, and storage conditions. In this study, we successfully determined the amino acid sequence and protein secondary structure model of non-glycosylated rhBMP-2 expressed by an E. coli expression system through X-ray crystal structure analysis. Furthermore, we observed that acidic storage conditions enhanced the proliferative and osteoinductive activity of rhBMP-2. Although the osteogenic activity of non-glycosylated rhBMP-2 is relatively weaker compared to glycosylated rhBMP-2; however, this discrepancy can be mitigated by incorporating exogenous chaperone molecules. Overall, such information is crucial for rationalizing the design of stabilization methods and enhancing the bioactivity of rhBMP-2, which may also be applicable to other growth factors.
RESUMEN
Objective: We compared the osteoblastogenesis by serially administrating recombinant human bone morphogenetic protein-2 (rhBMP-2) and osteoprotegerin-immunoglobulin Fc segment complex (OPG-Fc). Methods: The MC3T3-E1 preosteoblast cell line was differentiated for 1, 3, and 7 days with a treatment of OPG-Fc in 10~200 ng/mL concentration and the cell viability was evaluated by Cell Counting Kit-8 analysis. The level of differentiation from MC3T3-E1 cells to osteoblasts was determined by alkaline phosphatase activity. The level of runt domain-containing transcription factor 2 (Runx2) and osteopontin (OPN) manifestation, involved in osteoblast differentiation, was examined by real-time polymerase chain reaction and western blotting. Results: During MC3T3-E1 cell differentiation, the differentiation level was high with 1-day treatment using 100 ng/mL OPG-Fc. The treatment with 50 ng/mL rhBMP-2 for 7 days, followed by 1-day treatment with 100 ng/mL OPG-Fc produced the highest differentiation level, which was approximately 5.3 times that of the control group (p<0.05). The expression of Runx2 mRNA significantly increased, reaching 2.5 times the level of the control group under the condition of 7-day treatment with rhBMP-2 and 1-day treatment with OPG-Fc (p<0.001). The expression of Runx2 protein significantly increased to approximately 5.7 times that of the control group under the condition of 7-day treatment with rhBMP-2, followed by 1-day treatment with OPG-Fc (p<0.01). The expression of OPN protein showed no change from that of the control group under various conditions of rhBMP-2 and OPG-Fc combinations. Conclusion: These results imply that the treating preosteoblasts with rhBMP-2 first and then with OPG-Fc increased osteoblast differentiation efficacy.
RESUMEN
In Part II, we focus on an important aspect of spine fusion in patients with spine trauma: the pivotal role of recombinant human bone morphogenetic protein-2 (rhBMP-2). Despite the influx of diverse techniques facilitated by technological advancements in spinal surgery, spinal fusion surgery remains widely used globally. The persistent challenge of spinal pseudarthrosis has driven extensive efforts to achieve clinically favorable fusion outcomes, with particular emphasis on the evolution of bone graft substitutes. Part II of this review aims to build upon the foundation laid out in Part I by providing a comprehensive summary of commonly utilized bone graft substitutes for spinal fusion in patients with spinal trauma. Additionally, it will delve into the latest advancements and insights regarding the application of rhBMP-2, offering an updated perspective on its role in enhancing the success of spinal fusion procedures.
RESUMEN
OBJECTIVE: To report the operative outcomes after treating vertebral osteomyelitis patients with an anterior cervical corpectomy and fusion procedure using recombinant human bone morphogenetic protein-2 (rhBMP-2) as graft material. METHODS: A retrospective review of electronic medical records of 26 adult patients who underwent an anterior cervical corpectomy and fusion procedure for cervical osteomyelitis using rhBMP-2 at the University of Puerto Rico University District Hospital was performed. Indication, preoperative laboratory results, levels of corpectomy, preoperative American Spinal Injury Association Impairment Scale (ASIA) score, complications, fusion evaluation at 12 months, and ASIA score at 12 months were reviewed. RESULTS: For the cohort of patients, mean age was 47 ± 13 years and 65% were male. Spinal instability was present in 54%. The levels of corpectomy were: 1 level in 2 cases, 2 levels in 15 cases, 3 levels in 8 cases, and 5 levels in 1 case. Four patients had complications and, of these, 2 experienced dysphagia. The fusion rate was 100% and no reoperations were performed. An improvement in ASIA score was seen for 54% patients at 12-month follow-up. CONCLUSIONS: This study demonstrates a fusion rate of 100% with no reoperations reported. Recombinant human bone morphogenetic protein-2 could be considered and further researched as grafting material for anterior cervical corpectomy and fusion procedures in cervical osteomyelitis patients.
Asunto(s)
Proteína Morfogenética Ósea 2 , Vértebras Cervicales , Osteomielitis , Proteínas Recombinantes , Fusión Vertebral , Humanos , Masculino , Proteína Morfogenética Ósea 2/uso terapéutico , Fusión Vertebral/métodos , Persona de Mediana Edad , Osteomielitis/cirugía , Osteomielitis/tratamiento farmacológico , Femenino , Vértebras Cervicales/cirugía , Proteínas Recombinantes/uso terapéutico , Adulto , Estudios Retrospectivos , Resultado del Tratamiento , Factor de Crecimiento Transformador beta/uso terapéutico , AncianoRESUMEN
OBJECTIVE: To investigate the effect of bone cement containing recombinant human basic fibroblast growth factor (rhbFGF) and recombinant human bone morphogenetic protein-2 (rhBMP-2) in percutaneous kyphoplasty(PKP)treatment of osteoporotic vertebral compression fracture(OVCF). METHODS: A total of 103 OVCF patients who underwent PKP from January 2018 to January 2021 were retrospectively analyzed, including 40 males and 63 females, aged from 61 to 78 years old with an average of (65.72±3.29) years old. The injury mechanism included slipping 33 patients, falling 42 patients, and lifting injury 28 patients. The patients were divided into three groups according to the filling of bone cement. Calcium phosphate consisted of 34 patients, aged(65.1±3.3) years old, 14 males and 20 females, who were filled with calcium phosphate bone cement. rhBMP-2 consisted of 34 patients, aged (64.8±3.2) years old, 12 males and 22 females, who were filled with bone cement containing rhBMP-2. And rhbFGF+rhBMP-2 consisted of 35 patients, aged (65.1±3.6) years old, 14 males and 21 females, who were filled with bone cement containing rhbFGF and rhBMP-2. Oswestry disability index (ODI), bone mineral density, anterior edge loss height, anterior edge compression rate of injured vertebra, visual analog scale (VAS) of pain, and the incidence of refracture were compared between groups. RESULTS: All patients were followed for 12 months. Postoperative ODI and VAS score of the three groups decreased (P<0.001), while bone mineral density increased (P<0.001), anterior edge loss height, anterior edge compression rate of injured vertebra decreased first and then slowly increased (P<0.001). ODI and VAS of group calcium phosphate after 1 months, 6 months, 12 months were lower than that of rhBMP-2 and group rhbFGF+rhBMP-2(P<0.05), bone mineral density after 6 months, 12 months was higher than that of rhBMP-2 and group calcium phosphate(P<0.05), and anterior edge loss height, anterior edge compression rate of injured vertebra of group rhbFGF+rhBMP-2 after 6 months and 12 months were lower than that of group rhBMP-2 and group calcium phosphate(P<0.05). There was no statistical difference in the incidence of re-fracture among the three groups (P>0.05). CONCLUSION: Bone cement containing rhbFGF and rhBMP-2 could more effectively increase bone mineral density in patients with OVCF, obtain satisfactory clinical and radiological effects after operation, and significantly improve clinical symptoms.
Asunto(s)
Proteína Morfogenética Ósea 2 , Factor 2 de Crecimiento de Fibroblastos , Fracturas por Compresión , Cifoplastia , Fracturas Osteoporóticas , Proteínas Recombinantes , Fracturas de la Columna Vertebral , Factor de Crecimiento Transformador beta , Vertebroplastia , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Cementos para Huesos/uso terapéutico , Fracturas por Compresión/tratamiento farmacológico , Fracturas por Compresión/cirugía , Fracturas por Compresión/complicaciones , Estudios Retrospectivos , Fracturas de la Columna Vertebral/tratamiento farmacológico , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/complicaciones , Fracturas Osteoporóticas/tratamiento farmacológico , Fracturas Osteoporóticas/cirugía , Fracturas Osteoporóticas/etiología , Cifoplastia/efectos adversos , Vertebroplastia/efectos adversos , Fosfatos de Calcio/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE@#To investigate the effect of bone cement containing recombinant human basic fibroblast growth factor (rhbFGF) and recombinant human bone morphogenetic protein-2 (rhBMP-2) in percutaneous kyphoplasty(PKP)treatment of osteoporotic vertebral compression fracture(OVCF).@*METHODS@#A total of 103 OVCF patients who underwent PKP from January 2018 to January 2021 were retrospectively analyzed, including 40 males and 63 females, aged from 61 to 78 years old with an average of (65.72±3.29) years old. The injury mechanism included slipping 33 patients, falling 42 patients, and lifting injury 28 patients. The patients were divided into three groups according to the filling of bone cement. Calcium phosphate consisted of 34 patients, aged(65.1±3.3) years old, 14 males and 20 females, who were filled with calcium phosphate bone cement. rhBMP-2 consisted of 34 patients, aged (64.8±3.2) years old, 12 males and 22 females, who were filled with bone cement containing rhBMP-2. And rhbFGF+rhBMP-2 consisted of 35 patients, aged (65.1±3.6) years old, 14 males and 21 females, who were filled with bone cement containing rhbFGF and rhBMP-2. Oswestry disability index (ODI), bone mineral density, anterior edge loss height, anterior edge compression rate of injured vertebra, visual analog scale (VAS) of pain, and the incidence of refracture were compared between groups.@*RESULTS@#All patients were followed for 12 months. Postoperative ODI and VAS score of the three groups decreased (P<0.001), while bone mineral density increased (P<0.001), anterior edge loss height, anterior edge compression rate of injured vertebra decreased first and then slowly increased (P<0.001). ODI and VAS of group calcium phosphate after 1 months, 6 months, 12 months were lower than that of rhBMP-2 and group rhbFGF+rhBMP-2(P<0.05), bone mineral density after 6 months, 12 months was higher than that of rhBMP-2 and group calcium phosphate(P<0.05), and anterior edge loss height, anterior edge compression rate of injured vertebra of group rhbFGF+rhBMP-2 after 6 months and 12 months were lower than that of group rhBMP-2 and group calcium phosphate(P<0.05). There was no statistical difference in the incidence of re-fracture among the three groups (P>0.05).@*CONCLUSION@#Bone cement containing rhbFGF and rhBMP-2 could more effectively increase bone mineral density in patients with OVCF, obtain satisfactory clinical and radiological effects after operation, and significantly improve clinical symptoms.
Asunto(s)
Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Cementos para Huesos/uso terapéutico , Fracturas por Compresión/complicaciones , Estudios Retrospectivos , Fracturas de la Columna Vertebral/complicaciones , Fracturas Osteoporóticas/etiología , Cifoplastia/efectos adversos , Vertebroplastia/efectos adversos , Fosfatos de Calcio/uso terapéutico , Resultado del Tratamiento , Proteínas Recombinantes , Factor de Crecimiento Transformador beta , Factor 2 de Crecimiento de Fibroblastos , Proteína Morfogenética Ósea 2RESUMEN
BACKGROUND: rhBMP-2 is regarded as the most potent osteoinductive growth factor, and it has been used in the oral cavity with different carriers. The purpose of this study is to evaluate the bone-regenerative effect of rhBMP-2 delivered with different carrier systems through three-dimensional cone beam computed tomography analysis. METHOD: A total of 112 patients underwent oral surgery with rhBMP-2 application (Group 1, n = 53) or without rhBMP-2 application (Group 2, n = 59). Group 1 was divided into 3 groups according to carriers, rhBMP-2 with allograft (Group 1-1, n = 34), rhBMP-2 with xenograft (Group 1-2, n = 5), and rhBMP-2 with absorbable collagen sponge (Group 1-3, n = 14). Cone beam computed tomography scans were taken before surgery (T0) 6 months after surgery (T1). The volume of defects was measured through the three-dimensional image analysis tool. RESULTS: The average bone regeneration rate of Group 1 was significantly greater than that of Group 2. Within Group 1, the group that used allograft as a carrier (Group 1-1) showed significantly higher bone regeneration rates than the group that used absorbable collagen sponge as a carrier (Group 1-3). CONCLUSION: The use of rhBMP-2 after oral surgery results in a superior bone regeneration rate compared to not using rhBMP-2, and its efficacy depends on the carriers it is used with. Allograft affects bone regeneration more than absorbable collagen sponge when it is carried with rhBMP-2. Therefore, the appropriate use of rhBMP-2 with suitable bone grafting materials is useful for promoting postoperative bone regeneration in oral surgery.
RESUMEN
BACKGROUND: The authors report an Australian experience of lateral lumbar interbody fusion (LLIF) with respect to clinical outcomes, fusion rates, and complications, with recombinant human bone morphogenetic protein-2 (rhBMP-2) and other graft materials. METHODS: Retrospective cohort study of LLIF patients 2011-2021. LLIFs performed lateral decubitus by four experienced surgeons past their learning curve. Graft materials classified rhBMP-2 or non-rhBMP-2. Patient-reported outcomes assessed by VAS, ODI, and SF-12 preoperatively and postoperatively. Fusion rates assessed by CT postoperatively at 6 and 12 months. Complications classified minor or major. Clinical outcomes and complications analysed and compared between rhBMP-2 and non-rhBMP-2 groups. RESULTS: A cohort of 343 patients underwent 437 levels of LLIF. Mean age 67 ± 11 years (range 29-89) with a female preponderance (65%). Mean BMI 29kg/m2 (18-56). Most common operated levels L3/4 (36%) and L4/5 (35%). VAS, ODI and SF-12 improved significantly from baseline. Total complication rate 15% (53/343) with minor 11% (39/343) and major 4% (14/343). Ten patients returned to OR (2-wound infection, 8-further instrumentation and decompression). Most patients (264, 77%) received rhBMP-2, the remainder a non-rhBMP-2 graft material. No significant differences between groups at baseline. No increase in minor or major complications in the rhBMP-2 group compared to the non-rhBMP-2 group respectively; (10.6% vs 13.9% [p = 0.42], 2.7% vs 8.9% [p < 0.01]). Fusion rates significantly higher in the rhBMP-2 group at 6 and 12 months (63% vs 40%, [p < 0.01], 92% vs 80%, [p < 0.02]). CONCLUSION: LLIF is a safe and efficacious procedure. rhBMP-2 in LLIF produced earlier and higher fusion rates compared to available non-rhBMP-2 graft substitutes.
RESUMEN
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is one of the growth factors that may induce the formation of new bone. The aim was to determine the efficacy of low doses of rhBMP-2 for bone regeneration using a collagen sponge as a carrier. Three doses of rhBMP-2 (1.167, 0.117, and 0.039 mg/mL) were combined with an absorbable collagen sponge (ACS) as a delivery vehicle. The rhBMP-2/ACS implants were placed in the subcutaneous tissues of rat backs. X-ray microcomputed tomography (micro-CT) and histological analysis were used to evaluate bone formation. The samples treated with 1.167 mg/mL of rhBMP-2 showed greater bone formation than the samples treated with 0.117 mg/mL of rhBMP-2 four weeks after surgery. However, there was no evidence of bone formation in the samples that were treated with 0.039 mg/mL of rhBMP-2. It was found that rhBMP-2 was osteogenic even at one-tenth of its manufacturer's recommended concentration (1.167 mg/mL), indicating its potential for clinical use at lower concentrations.
Asunto(s)
Proteína Morfogenética Ósea 2 , Factor de Crecimiento Transformador beta , Humanos , Ratas , Animales , Microtomografía por Rayos X , Factor de Crecimiento Transformador beta/farmacología , Factor de Crecimiento Transformador beta/uso terapéutico , Proteína Morfogenética Ósea 2/farmacología , Colágeno/farmacología , Proteínas Recombinantes/farmacología , Regeneración Ósea , Implantes AbsorbiblesRESUMEN
This study defined and compared the course of native, impaired and growth factor-stimulated bone regeneration in a rat femoral defect model. A mid-diaphyseal defect with rigid internal fixation was surgically created in the right femur of male Fischer rats and serially analyzed over 36 weeks. Native bone regeneration was modeled using a sub-critical, 1 mm size defect, which healed uneventfully. Critical size defects of 5 mm were used to analyze impaired bone regeneration. In a third group, the 5 mm defects were filled with 11 µg of recombinant human bone morphogenetic protein 2 (rhBMP2) impregnated onto an absorbable collagen sponge, modeling its clinical use. Native bone regeneration was characterized by endochondral ossification with progressive remodeling to ultimately resemble intact femora. An endochondral response was also observed under conditions of impaired bone regeneration, but by week 8 medullary capping occurred with fibrofatty consolidation of the tissue within the defect, resembling an atrophic non-union. rhBMP2 treatment was associated with prolonged inflammatory cytokine expression and rapid intramembranous bone formation occurring with reduced expression of cartilage-associated collagens. Between weeks 4 and 36, rhBMP2-treated bones demonstrated decreased trabecular number and increased trabecular separation, which resulted in inferior mechanical properties compared with bones that healed naturally. Clinical Significance: Recombinant human bone morphogenetic protein 2 (rhBMP2) is used clinically to promote healing of long bones. Our data suggest that it drives intramembraneous ossification producing an inferior regenerate that deteriorates with time. Clinical outcomes would be improved by technologies favoring endochondral regenerative ossification.
Asunto(s)
Proteína Morfogenética Ósea 2 , Regeneración Ósea , Ratas , Humanos , Masculino , Animales , Proteína Morfogenética Ósea 2/farmacología , Proteína Morfogenética Ósea 2/uso terapéutico , Cicatrización de Heridas , Fémur , Osteogénesis , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéuticoRESUMEN
Bone morphogenetic protein-2 (BMP-2) is used in the treatment of degenerative spinal disease and vertebral fractures, spine fusion, dental surgery, and facial surgery. However, high doses are associated with side effects such as inflammation and osteophytes. In this study, we performed spinal fusion surgery on mini-pigs using BMP-2 and a HA/ß-TCP hydrogel carrier, and evaluated the degree of fusion and osteophyte growth according to time and dosage. Increasing the dose of BMP-2 led to a significantly higher fusion rate than was observed in the control group, and there was no significant difference between the 8-week and 16-week samples. We also found that the HA + ß-TCP hydrogel combination helped maintain the rate of BMP-2 release. In conclusion, the BMP-2-loaded HA/ß-TCP hydrogel carrier used in this study overcame the drawback of potentially causing side effects when used at high concentrations by enabling the sustained release of BMP-2. This method is also highly efficient, since it provides mineral matter to accelerate the fusion rate of the spine and improve bone quality.
Asunto(s)
Proteína Morfogenética Ósea 2 , Proteínas Recombinantes , Fusión Vertebral , Animales , Humanos , Proteína Morfogenética Ósea 2/uso terapéutico , Hidrogeles , Proteínas Recombinantes/uso terapéutico , Fusión Vertebral/métodos , Porcinos , Porcinos Enanos , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways. Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSCBMP2) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSCBMP2 were associated with migration and growth. MSCBMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSCBMP2. MSCBMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3+CD25+ Treg of CD4+ cells were further increased in ALI mice treated with MSCBMP2. In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSCBMP2. Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSCBMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.
RESUMEN
Bone marrow-derived mesenchymal stem cells (BM-MSCs) play a crucial role in stem cell therapy and are extensively used in regenerative medicine research. However, current methods for harvesting BM-MSCs present challenges, including a low yield of primary cells, long time of in vitro expansion, and diminished differentiation capability after passaging. Meanwhile mesenchymal stem cells (MSCs) recovered from cell banks also face issues like toxic effects of cryopreservation media. In this study, we provide a detailed protocol for the isolation and evaluation of MSCs derived from in vivo osteo-organoids, presenting an alternative to autologous MSCs. We used recombinant human bone morphogenetic protein 2-loaded gelatin sponge scaffolds to construct in vivo osteo-organoids, which were stable sources of MSCs with large quantity, high purity, and strong stemness. Compared with protocols using bone marrow, our protocol can obtain large numbers of high-purity MSCs in a shorter time (6 days vs. 12 days for obtaining passage 1 MSCs) while maintaining higher stemness. Notably, we found that the in vivo osteo-organoid-derived MSCs exhibited stronger anti-replicative senescence capacity during passage and amplification, compared to BM-MSCs. The use of osteo-organoid-derived MSCs addresses the conflict between the limitations of autologous cells and the risks associated with allogeneic sources in stem cell transplantation. Consequently, our protocol emerges as a superior alternative for both stem cell research and tissue engineering.
RESUMEN
PURPOSE: After extracting impacted mandibular third molars (IMM3), the resulting bone loss at the distal surface of the distal root of mandibular second molars (MM2) is responsible for the poor stability of MM2. This study aimed to identify the clinical osteogenesis effect of recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium phosphate cements (CPCs) and rhBMP-2 delivery systems (rhBMP-2/CPCs, named CPCII) on bone loss repair at the distal surface of the MM2 distal root after IMM3 extraction. METHODS: Written informed consent was obtained from every participant whose IMM3 needed extraction. The impact of IMM3 on both sides was basically identical. From April 2014 to March 2016, extraction of IMM3 was performed in 9 patients (5 males/4 females, 26-42 years old). One side was randomly selected as the experimental group, and CPCII systems were implanted into the distal surface of the distal root in dental extraction sockets. The wounds on the other side were sutured and allowed to heal naturally (be treated as the control group). New bone formation in the alveolar fossa was detected 3 and 12 months after the operation by cone-beam computed tomography (CBCT) to measure the distance from the cementoenamel junction (CEJ) to the crest of the alveolar ridge (CAR). RESULTS: The CAR-CEJ distance on the test side was less than that on the control side (P<0.5). CONCLUSION: The quantity of new bone formation in the experimental group was greater than that in the control group. CPCII systems have osteogenic potential in the healing process of tooth extraction sockets.
RESUMEN
Objective: To investigate the optimal mixing ratio of recombinant human bone morphogenetic protein 2 (rhBMP-2) with porous calcium phosphate cement (PCPC) and autologous bone as bone grafting material for the repair of large bone defects using Masquelet technique. The effect of platelet-rich plasma (PRP) on the healing of bone defects was evaluated under the optimal ratio of mixed bone. Methods: Fifty-four New Zealand White rabbits were taken to establish a 2 cm long bone defect model of the ulna and treated using the Masquelet technique. Two parts of the experiment were performed in the second phase of the Masquelet technique. First, 36 modeled experimental animals were randomly divided into 4 groups ( n=9) according to the mass ratio of autologous bone and rhBMP-2/PCPC. Group A: autologous bone (100%); group B: 25% autologous bone+75% rhBMP-2/PCPC; group C: 50% autologous bone+50% rhBMP-2/PCPC; group D: 75% autologous bone+25% rhBMP-2/PCPC. The animals were executed at 4, 8, and 12 weeks postoperatively for general observation, imaging observation, histological observation (HE staining), alkaline phosphatase (ALP) activity assay, and biomechanical assay (three-point bending test) were performed to assess the osteogenic ability and to determine the optimal mixing ratio. Then, 18 modeled experimental animals were randomly divided into 2 groups ( n=9). The control group was implanted with the optimal mixture ratio of autologous bone+rhBMP-2/PCPC, and the experimental group was implanted with the optimal mixture ratio of autologous bone+rhBMP-2/PCPC+autologous PRP. The same method was used to observe the above indexes at 4, 8, and 12 weeks postoperatively. Results: The bone healing process from callus formation to the cortical connection at the defected gap could be observed in each group after operation; new bone formation, bridging with the host bone, and bone remodeling to normal bone density were observed on imaging observation; new woven bone, new capillaries, bone marrow cavity, and other structures were observed on histological observation. The ALP activity of each group gradually increased with time ( P<0.05); the ALP activity of group A was significantly higher than that of the other 3 groups at each time point after operation, and of groups C and D than group B ( P<0.05); there was no significant difference between groups C and D ( P>0.05). Biomechanical assay showed that the maximum load in three-point bending test of each group increased gradually with time ( P<0.05), and the maximum loads of groups A and D were significantly higher than that of groups B and C at each time point after operation ( P<0.05), but there was no significant difference between groups A and D ( P>0.05). According to the above tests, the optimal mixing ratio was 75% autogenous bone+25% rhBMP-2/PCPC. The process of new bone formation in the experimental group and the control group was observed by gross observation, imaging examination, and histological observation, and the ability of bone formation in the experimental group was better than that in the control group. The ALP activity and maximum load increased gradually with time in both groups ( P<0.05); the ALP activity and maximum load in the experimental group were significantly higher than those in the control group at each time point after operation ( P<0.05), and the maximum load in the experimental group was also significantly higher than that in group A at 12 weeks after operation ( P<0.05). Conclusion: In the second phase of Masquelet technique, rhBMP-2/PCPC mixed with autologous bone to fill the bone defect can treat large bone defect of rabbit ulna, and it has the best osteogenic ability when the mixing ratio is 75% autologous bone+25% rhBMP-2/PCPC. The combination of PRP can improve the osteogenic ability of rhBMP-2/PCPC and autologous bone mixture.
Asunto(s)
Proteína Morfogenética Ósea 2 , Plasma Rico en Plaquetas , Animales , Humanos , Conejos , Cementos para Huesos/uso terapéutico , Fosfatos de Calcio , Fosfatos , Porosidad , Proteínas Recombinantes , Factor de Crecimiento Transformador betaRESUMEN
BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used as an alternative bone graft in spine fusion surgery. However, clinical outcome such as effects and complications has not yet been revealed for transforaminal lumbar interbody fusion (TLIF). Although previous studies have reported some results, the evidence is weak. Therefore, the purpose of this trial is to evaluate the effectiveness and safety of Escherichia coli-derived rhBMP-2 combined with hydroxyapatite (HA) in TLIF. METHODS: This trial is designed as a prospective, assessor-blinded, open-label, multicenter, randomized controlled study. Participants will be recruited from six tertiary teaching hospitals. All randomized participants will be undergoing one- or two-level TLIF with rhBMP-2 (77 participants) as the active experimental group or with an auto-iliac bone graft (77 participants) as the control group. The primary interbody fusion rate outcome will be evaluated using computed tomography (CT) 12 months after surgery. The secondary outcomes will be as follows: clinical outcomes (visual analog scale score, EuroQol-5-dimensions-5-level score, Oswestry Disability Index score, and some surgery-related variables) and adverse effects (radiculitis, heterotrophic ossification, endplate resorption, and osteolysis). Radiological outcomes will be evaluated using simple radiography or CT. All outcomes will be measured, collected, and evaluated before surgery and at 12, 24, and 52 weeks postoperatively. DISCUSSION: This study will be the primary of its kind to evaluate the effectiveness and safety of E. coli-derived rhBMP-2 with HA in one- or two-level TLIF. It is designed to evaluate the equivalence of the results between rhBMP-2 with HA and auto-iliac bone graft using an appropriate sample size, assessor-blinded analyses, and prospective registration to avoid bias. This study will set up clear conclusions for using E. coli-derived rhBMP-2 with HA in TLIF. TRIAL REGISTRATION: This study protocol was registered at Korea Clinical Research Information Service ( https://cris.nih.go.kr ; number identifier: KCT0005610) on 19 November 2020. And protocol version is v1.1, January 2022.
Asunto(s)
Enfermedades de la Columna Vertebral , Fusión Vertebral , Proteína Morfogenética Ósea 2/efectos adversos , Durapatita , Escherichia coli , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Estudios Multicéntricos como Asunto , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes/efectos adversos , Enfermedades de la Columna Vertebral/tratamiento farmacológico , Fusión Vertebral/métodos , Factor de Crecimiento Transformador beta/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Periosteum plays a significant role in bone formation and regeneration by storing progenitor cells, and also acts as a source of local growth factors and a scaffold for recruiting cells and other growth factors. Recently, tissue-engineered periosteum has been studied extensively and shown to be important for osteogenesis and chondrogenesis. Using biomimetic methods for artificial periosteum synthesis, membranous tissues with similar function and structure to native periosteum are produced that significantly improve the efficacy of bone grafting and scaffold engineering, and can serve as direct replacements for native periosteum. Many problems involving bone defects can be solved by preparation of idealized periosteum from materials with different properties using various techniques. METHODS: This review summarizes the significance of periosteum for osteogenesis and chondrogenesis from the aspects of periosteum tissue structure, osteogenesis performance, clinical application, and development of periosteum tissue engineering. The advantages and disadvantages of different tissue engineering methods are also summarized. RESULTS: The fast-developing field of periosteum tissue engineering is aimed toward synthesis of bionic periosteum that can ensure or accelerate the repair of bone defects. Artificial periosteum materials can be similar to natural periosteum in both structure and function, and have good therapeutic potential. Induction of periosteum tissue regeneration and bone regeneration by biomimetic periosteum is the ideal process for bone repair. CONCLUSIONS: Periosteum is essential for bone formation and regeneration, and it is indispensable in bone repair. Achieving personalized structure and composition in the construction of tissue engineering periosteum is in accordance with the design concept of both universality and emphasis on individual differences and ensures the combination of commonness and individuality, which are expected to meet the clinical needs of bone repair more effectively. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: To better understand the role of periosteum in bone repair, clarify the present research situation of periosteum and tissue engineering periosteum, and determine the development and optimization direction of tissue engineering periosteum in the future. It is hoped that periosteum tissue engineering will play a greater role in meeting the clinical needs of bone repair in the future, and makes it possible to achieve optimization of bone tissue therapy.
RESUMEN
Background and Objective: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been extensively studied in preclinical, animal, and human studies and has been used widely in spine fusion surgery. Evidence demonstrates that fusion rates with rhBMP-2 are similar to or higher than those achieved with autologous bone graft. However, there have been concerns regarding the cost, optimal dosage, and potential complications of rhBMP-2 use in spine surgery. The objective of this paper is to provide a current review of the available evidence regarding rhBMP-2 and other bone graft substitutes used for spinal surgery. Methods: We searched Ovid Medline, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, American College of Physicians Journal Club, and Database of Abstracts of Review of Effectiveness for 2 studies regarding physiology of bone fusion in spine surgery, formulations and indications of rhBMP-2, cancer risk of rhBMP-2, and alternatives to rhBMP-2 published from 1965 to 2022 in English. Key Content and Findings: The debate regarding indications and cost effectiveness of rhBMP-2 is presented based on increasing data and use criteria. Here, we focus on the effectiveness and economic costs (both direct and indirect) of rhBMP-2 and alternative bone graft substitutes. Based on the cumulative literature, we provide recommendations for rhBMP-2 use in spine surgery. Conclusions: Based on our review of the literature, we recommend the following: (I) clear informed consent processes between surgeons and patients regarding current evidence of the benefits and risks of using rhBMP-2 and available alternative bone graft substitutes. (II) Consideration of rhBMP-2 for spinal fusion surgery (excluding anterior cervical procedures), especially adult spinal deformity (ASD) surgery, lumbar surgery for multilevel degenerative disease, revision surgery for pseudoarthrosis, and surgery in patients with a low-quantity or low-quality autograft. (III) Regulatory oversight of the type, volume, and dose of bone graft substitute (both per level and per procedure) to ensure appropriate indications, prevent excessive usage, and thereby enhance cost containment.
RESUMEN
This study evaluated 3D printed polycaprolactone (PCL) composite scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2), loaded either onto a PCL composite scaffold or implant surface, for vertical bone augmentation with implant placement. Three-dimensional printed PCL frames were filled with powdered PCL, hydroxyapatite, and ß-tricalcium phosphate. RhBMP-2 was loaded to the PCL composite scaffolds and implant surfaces, and rhBMP-2 release was quantified for 21 days. Experimental implants were placed bilaterally on 20 rabbit calvaria, and the PCL composite scaffolds were vertically augmented. The randomly allocated experimental groups were divided by carrier and rhBMP-2 dosage as no rhBMP-2 (control), 5 µg rhBMP-2 loaded to PCL composite (Scaffold/rhBMP-2[5 µg]), 5 µg rhBMP-2 loaded to implant (Implant/rhBMP-2[5 µg]), 30 µg rhBMP-2 loaded to PCL composite (Scaffold/rhBMP-2[30 µg]), and 30 µg rhBMP-2 loaded to implant (Implant/rhBMP-2[30 µg]). Histologic and histometric analyses were conducted after 8 weeks. In both scaffold-loading and implant-loading, rhBMP-2 released initially rapidly, then slowly and constantly. Released rhBMP-2 totaled 23.02 ± 1.03% and 24.69 ± 1.14% in the scaffold-loaded and implant-loaded groups, respectively. There were no significant differences in histologic bone-implant contact (%). Peri-implant bone density (%) was significantly higher in the Scaffold/rhBMP-2(30 µg) and Implant/rhBMP-2(30 µg) groups. Total bone density (%) was not significantly different between the Scaffold/rhBMP-2(5 µg), Implant/rhBMP-2(5 µg), and control groups, or between the Scaffold/rhBMP-2(30 µg) and Implant/rhBMP-2(30 µg) groups, but was significantly higher in the Scaffold/rhBMP-2(30 µg) and Implant/rhBMP-2(30 µg) groups than in the controls. Three-dimensional printed PCL composite scaffold with rhBMP-2 produced vertical osteogenesis and osseointegration, regardless of rhBMP-2 loading to the PCL composite scaffold or implant surface.
Asunto(s)
Proteína Morfogenética Ósea 2 , Factor de Crecimiento Transformador beta , Animales , Humanos , Conejos , Proteína Morfogenética Ósea 2/farmacología , Regeneración Ósea , Oseointegración , Osteogénesis , Poliésteres , Impresión Tridimensional , Proteínas Recombinantes/farmacología , Cráneo , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
OBJECTIVE: To compare the results of interbody fusion in patients undergoing minimally invasive lateral lumbar interbody fusion (LLIF) using demineralized bone matrix (DBM) alone versus DBM+recombinant human bone morphogenetic protein-2 (rhBMP2). METHODS: This retrospective case-controlled study was conducted in patients undergoing minimally invasive LLIF (n = 54) for lumbar interbody fusion; they were divided into 2 groups: DBM-only group and DMB+rhBMP2 group. The improvements of segmental and lumbar lordosis and restoration of disc height were measured, and the interbody fusion rates were determined using a modified Bridwell grading system. Clinical outcomes after surgery, such as visual analog scale scores of back pain and leg pain, and Oswestry disability index were compared. RESULTS: There were no significant differences in disc height, lumbar and segmental lordosis, or interbody fusion rate between the 2 groups. However, the proportion of Bridwell grade 1 as complete interbody bridging was higher in the DBM+rhBMP2 group than in the DBM-only group at both 6 and 12 months (P < 0.001). Clinical parameters showed equally significant improvement during follow-up in both groups, with no significant differences between the groups. CONCLUSION: In minimally invasive LLIF, adding Escherichia coli-derived rhBMP2 to DBM did not affect clinical outcomes or radiation parameters, but increased the speed of fusion and interbody bony bridging rate.