Serum Bone Morphogenetic Protein-2 Research Articles

Effect of Mongolian medicine alcohol spray therapy on fracture healing in rabbits

Purpose: To evaluate the healing effect and mechanism of Mongolian medicine alcohol spray therapy on fracture healing process in rabbits.
 Methods: Thirty New Zealand white rabbits were randomly divided into normal, fracture, and treatment groups, with 10 rabbits in each group. Fracture and treatment groups underwent bone-fracture modeling, with the latter receiving daily alcohol spraying and stroking for six weeks. Serum calcium and phosphorus were measured using an automatic biochemical analyzer. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of BMP-2, ALP, and TGF-β. Biomechanical testing was performed to assess callus properties, and real-time polymerase chain reaction (PCR) and western blot were performed to assess BMP-2, Runx2, and p-Smad1/5 expressions in callus.
 Results: There were low serum calcium, phosphorus, BMP-2, ALP, and TGF-β levels in fracture and treatment groups, compared to normal group. Similarly, treatment group showed significantly increased levels of serum calcium, phosphorus, bone morphogenetic protein 2 (BMP-2), alkaline phosphatase (ALP), and transforming growth factor-β (TGF-β) (p < 0.05) compared to fracture group. Biomechanical testing revealed that maximum load, stiffness, and deflection of callus in the fracture and treatment groups were significantly lower compared to normal group (p < 0.05). expressions of BMP-2, Runx2, and p-Smad1/5 mRNA in the callus significantly decreased in both fracture and treatment groups compared to normal group (p < 0.05). However, treatment group showed significantly increased expression levels compared to fracture group (p < 0.05).
 Conclusion: Mongolian medicine alcohol spray therapy promotes fracture healing in rabbits and increases maximum load of the callus, possibly through upregulation of the BMP-2 signaling pathway. Further research is necessary to confirm the exact mechanism by which alcohol spray therapy regulates BMP-2 signaling pathway.

Serum BMP-2 and osteocalcin levels, and CT Hounsfield unit post hyperbaric oxygen therapy in patients with cleft lip and palate post alveolar bone graft: A case study

BackgroundThis study investigated the levels of bone morphogenetic protein 2 (BMP-2), osteocalcin, and 3D CT Hounsfield units following hyperbaric oxygen therapy (HBOT) in patients with cleft lip and palate (CLP) undergoing alveolar bone grafts to provide a pilot evaluation of the role of HBOT in osteogenesis. MethodsThis prospective, quasi-experimental, pre–post-intervention study evaluated seven patients with CLP receiving HBOT after single-stage reconstructions with alveolar bone grafts. The outcomes included the serum levels of BMP-2 and osteocalcin and the 3D CT Hounsfield units obtained before and after the surgery, and after the five HBOT sessions, to a total of 12 measurements. The data were analyzed with linear mixed-effects models using the intervention stage (pre-surgery, pre-HBOT, first to fifth HBOT sessions) as covariates and adjusting for several baseline factors. ResultsA significant difference was found in outcome measures across time (ANOVA p < 0.001 for BMP-2 and osteocalcin, p = 0.01 for Hounsfield units), with mean values appearing to steadily increase once HBOT began. Regression analyses indicated that the effect of HBOT was evident in serum osteocalcin after the 1st HBOT session (adjusted b = 1.32; 95% CI 0.39, 2.25) and in serum BMP-2 after the third session (adjusted b = 6.61; 95% CI 1.93, 11.28). After the fifth session, the HBOT effect was fairly pronounced on the two outcomes: the adjusted increase compared to the baseline was 28.06 ng/mL for BMP-2 and 6.27 ng/mL for osteocalcin. Our mixed-effect models also showed a post-HBOT increase in Hounsfield units. ConclusionWe found an increase of BMP-2, osteocalcin, and Hounsfield units following the HBOT intervention. These may suggest an effect of HBOT on osteogenesis.

Effect of Moxibustion Instrument Combined with Intermediate Frequency Electrostatic Therapy on Pain and Joint Function in Elderly Patients with Cold-Dampness Knee Arthritis.

Objective To explore the effect of a moxibustion instrument combined with intermediate frequency electrostatic therapy on pain and joint function in elderly patients with cold-dampness arthritis (KOA). Method 200 patients with cold-dampness KOA treated in our hospital from May 2019 to September 2021 were selected. According to the random number table method, they were divided into the observation group (n = 100) and control group (n = 100). The observation group was treated with moxibustion combined with medium-frequency treatment, and the control group was treated with medium-frequency treatment. The clinical effects of the two groups were compared. The joint functions of the two groups were evaluated by the visualization scale of the osteoarthritis index (WOMAC index) of McMaster University in Western Ontario. The TCM symptom scores of the two groups were evaluated according to the guiding principles for clinical research of new traditional Chinese medicine. The visual analogue scale (VAS) was used to evaluate the pain degree of the two groups, and the microcirculatory blood perfusion (MBPU) and interleukin-1 were compared between the two groups, β (IL-1β) and tumor necrosis factor-α (TNF-α). The levels of matrix metalloproteinase-1 (MMP-1), serum bone morphogenetic protein-2 (BMP-2), cartilage oligomeric matrix protein (COMP), and serum type II collagen C-terminal peptide (CTX-II) were assessed by the comprehensive quality of life questionnaire-74. Result The total effective rate of the observation group (92.00%) was higher than that of the control group (76.00%), and the difference was statistically significant (P < 0.05) in β and TNF-α. The levels of MMP-3, BMP-2, comp, and CTX-II and the improvement of quality of life score in the control group were better than those in the control group (P < 0.05). Conclusion Moxibustion instrument combined with intermediate frequency electrostatic therapy can effectively improve the knee joint function, pain, blood perfusion, inflammatory reaction, and cartilage damage of the elderly patients with cold-dampness-type knee arthritis, and the therapeutic effect is good.

The WNT/β-catenin signalling pathway induces chondrocyte apoptosis in the cartilage injury caused by T-2 toxin in rats

We investigated whether the WNT/β-catenin signalling pathway is involved in paediatric Kashin–Beck disease (KBD) and T-2-toxin-induced cartilage injury in rats to better understand the mechanism of KBD. One hundred twenty-two children were selected and assigned to the case (31), internal control (41), and external control (50) groups. The serum β-catenin and bone morphogenetic protein 2（BMP2）levels in each group were measured and compared. Thirty-six rats were randomly assigned to three groups, which received no intervention, T-2 toxin, or solvent. After 18 weeks, the expression of LDL receptor related proteins 5 (LRP5), β-catenin, BMP2, BAX, BCL2, APAF1, and caspase 9 was measured and compared. The serum BMP2 levels were significantly elevated in the children with KBD and in the rats treated with T-2 toxin. In the T-2 toxin group, LRP5 and β-catenin expression was reduced, whereas BAX, APAF1, and caspase 9 expression was increased. In conclusion, the WNT/β-catenin signalling pathway is suppressed in KBD, which induces chondrocyte apoptosis, leading to cartilage injury. Therefore, BMP2 may play a role in the pathogenesis of KBD.

Effects of ergosteroside combined risedronate on fracture healing and BMP-2, BMP-7 and VEGF expression in rats.

ABSTRACTPurposeTo evaluate the effect of ergosterol combined with risedronate on fracture healing.MethodsSixty male Sprague Dawley fracture model rats were assigned into group A (n=20), group B (n=20), and group C (n=20) at random. All rats were fed by gavage until their sacrifice as it follows: group A with ergosteroside and risedronate, group B with risedronate, and group C with saline solution. At weeks 2 and 4, 10 rats of each group were sacrificed. Healing effect and bone tissue changes in the fractures site were assessed by using hematoxylin and eosin stain histology. Enzyme-linked immunosorbent assay was used to detect the expression of serum bone morphogenetic protein-2 (BMP-2), bone morphogenetic protein-7 (BMP-7), and vascular endothelial growth factor (VEGF). Reverse transcriptase polymerase chain reaction was applied to detect the expression of osteoprotegerin (OPG) mRNA, osteocalcin (OCN) mRNA and core-binding factor subunit-?1 (CBF-?1) mRNA.ResultsIn terms of serum BMP-2, BMP-7, and VEGF expression at weeks 2 and 4 after gavage, group A < group B < group C (P<0.05). At week 4 after gavage, serum VEGF expression in the three groups harbored positive relationship with serum BMP-2 and BMP-7 expression (P<0.05). Regarding serum OPG, OCN and CBF-?1 mRNA expression at weeks 2 and 4 after gavage, group A <group B <group C (P<0.05). Hematoxylin and eosin staining results showed that the recovery effect of trabecular bone and callus in the cases of group A was better than the other two groups after intragastric administration.ConclusionErgosteroside combined risedronate can patently ameliorate the healing effect of fracture in rats.

Shockwave Therapy Modulates the Expression of BMP2 for Prevention of Bone and Cartilage Loss in the Lower Limbs of Postmenopausal Osteoporosis Rat Model

Osteoporosis (OP) causes bone loss and weakness, increasing the risk of bone fracture. In this study, rats were divided into Sham, OP, SW(F) (0.25 mJ/mm2 with 1600 impulses to the left medial femur), and SW(T) (0.25 mJ/mm2 with 1600 impulses to the left medial tibia). The bone strength results following SW(T) were better than SW(F) in the modulus, extension at peak load, handleability, and strain at break. SW(T) had the best prevention for bone loss in both lower limbs of ovariectomized (OVX) rats. The cartilage cellular matrixes of both knees were improved in SW(T) and SW(F) compared to that of OP. Serum bone morphogenetic protein 2 (BMP2) in rats undergoing SW(T) or SW(F) was significantly improved compared to that in Sham and OP. The expressions of BMP2, BMP4, and SMAD family member 4 (Smad4) in addition to the Wnt family member 3A (Wnt3a) and Cyclin D1 signaling key factors were significantly induced in the cartilage of both knees by shockwave (SW). SW(T) presented the best efficacy to induce serum BMP2 to prevent bone loss from both lower limbs. Here, we display the protective effects of SW therapy to induce BMP2, BMP4, Smad4, Wnt3a, and Cyclin D1 signaling factors for cartilage loss in both knees of OVX rats.

Serum miRNA-142 and BMP-2 are markers of recovery following hip replacement surgery for femoral neck fracture.

The present study aimed to investigate the changes in miRNA-142 and bone morphogenetic protein-2 (BMP-2) expression before and after hip replacement surgery, and to determine their association with receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). For this purpose, 142 cases of hip arthroplasty in patients with femoral neck fracture were selected as the research group, and 50 cases of healthy individuals who underwent a physical examination during the same time period were selected the control group. Serum miR-142 and BMP-2 levels were measured by RT-qPCR before and after surgery in the research group and the control group. Serum RANKL and OPG levels were detected before and after surgery by enzyme-linked immunosorbent assay (ELISA). The levels of serum miR-142 and BMP-2 in the research group were significantly lower than those in the control group. At 1 month after surgery, the levels of serum miR-142 and BMP-2 in the research group were significantly higher than those before surgery, and at 6 months after surgery, and they were higher than those in the control group. Pearson's correlation analysis revealed that the serum levels of miR-142 positively correlated with the BMP-2 levels before surgery, at 1 month after surgery, and at 6 months after surgery in the research group. The results of ROC curve analysis revealed that the AUC values of serum miR-142 and BMP-2 were 0.911 and 0.861, respectively. At 1 month after surgery, the levels of serum miR-142 and BMP-2 in group A (patients with a good or excellent recovery) were significantly higher than those in group B (patients with a fair or poor recovery). The levels of serum RANKL and OPG in the research group significantly increased at 1 month after surgery. The serum levels of miR-142 and BMP-2 positively correlated with those of RANKL and OPG before surgery and at 1 month after surgery. On the whole, the findings of the present study indicate that pre-operative serum miR-142 and BMP-2 levels are valuable for evaluating the post-operative recovery of patients with femoral neck fracture undergoing hip replacement surgery. In addition, in the present study, at 1 month after surgery, the levels of both miR-142 and BMP-2 were related to the recovery of the patients, and positively correlated with the RANKL and OPG levels.

Therapeutic effect of heat-sensitive moxibustion plus medications for senile osteoporosis and its effect on serum BMP-2 and OPG levels

To observe the clinical efficacy of heat-sensitive moxibustion plus medications on senile osteoporosis (SOP), and to explore the related mechanisms. A total of 70 elderly participants with osteoporosis were randomly divided into an observation group and control group, with 35 cases in each group. The control group was treated with conventional drugs, and the observation group was treated with heat-sensitive moxibustion on the basis of the conventional drugs. Both groups were treated for 3 months. Before and after treatment, assessed the visual analog scale (VAS) and Oswestry disability index (ODI) scores, determined the bone mineral density of the participants’ lumbar spine (L2-L4) and left femoral neck, and detected the participants’ serum bone morphogenetic protein-2 (BMP-2) and osteoprotegerin (OPG) levels. After treatment, the VAS scores of both groups were lower than before treatment (both P<0.05), and the VAS score of the observation group was significantly lower than that of the control group (P<0.05). After treatment, the bone mineral density values of the lumbar spine and left femoral neck in both groups were significantly higher than before treatment (both P<0.05), and the bone mineral density values of the observation group were higher than those of the control group (P<0.05). After treatment, the ODI scores of the two groups were lower than those before treatment (both P<0.05), and the ODI score of the observation group was lower than that of the control group (P<0.05). After treatment, the serum BMP-2 and OPG levels in the observation group were significantly higher than those in the control group (both P<0.05). Heat-sensitive moxibustion plus medications for SOP can significantly relieve patients’ pain, improve dysfunction, and increase bone density, which may be related to the improvement of the serum BMP-2 and OPG levels.

Serum Sclerostin and Bone Morphogenetic Protein-2 Levels in Patients with Ankylosing Spondylitis: A Meta-Analysis.

Various studies have investigated the serum sclerostin and bone morphogenetic protein-2 (BMP-2) levels in patients with ankylosing spondylitis (AS), but the results were inconsistent. The aim of this meta-analysis was to synthetically assess the associations of serum levels of sclerostin and BMP-2 with AS. Multiple electronic databases were searched to locate relevant articles published before November 2018. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Totally, 21 studies were included. Meta-analysis results showed no significant difference between AS group and control group in serum sclerostin levels (SMD = 0.098, 95% CI - 0.395 to 0.591, p = 0.697). Nevertheless, serum BMP-2 levels in AS patients were higher than that in controls (SMD = 1.184, 95% CI 0.209 to 2.159, p = 0.017). Subgroup analysis demonstrated that European and South American AS patients had lower serum levels of sclerostin than controls. AS patients with age ≥ 40 years, erythrocyte sedimentation rate (ESR) ≤ 20mm/h and Bath Ankylosing Spondylitis Functional Index (BASFI) < 4 had statistically significant lower serum sclerostin concentrations compared to controls. Chinese and Korean AS patients as well as patients with lower CRP had higher serum BMP-2 levels than controls, and country may be a source of heterogeneity across the studies. No publication bias existed and sensitivity analysis confirmed the stability of results. Serum BMP-2, but not sclerostin levels may be closely related to the development of AS.

Effects of the combined Herba Epimedii and Fructus Ligustri Lucidi on bone turnover and TGF-β1/Smads pathway in GIOP rats

Ethnopharmacological relevanceKidney deficiency is the main pathogenesis of osteoporosis based on the theory of “kidney governing bones” in traditional Chinese medicine (TCM). Combined Herba Epimedii and Fructus Ligustri Lucidi, based on traditional Chinese formula Er-Zhi pills, were frequently used in TCM formulas that were prescribed for kidney tonifying and bone strengthening. However, it is unclear whether the combination of the two herbs may have a protective influence on glucocorticoid-induced osteoporosis (GIOP). The objective of this study was to evaluate the therapeutic effects and the underlying molecular mechanism of the decoction and the active fractions of the combined herbs in GIOP rats. Materials and methodsMale Sprague-Dawley rats were divided into seven groups, including the normal control (NC), GIOP model (MO), active fractions low (100mg/kg, LAF), active fractions high (200mg/kg, HAF), decoction low (3.5g/kg, LD), decoction high (7g/kg, HD) and Calcium with Vitamin D3 (0.2773g/kg, CaD)-treated group. The GIOP model was established by intramuscular injection of dexamethasone (1mg/kg) twice a week for 8 weeks. Different kinds of indicators were measured, including bone mineral density (BMD), bone biomechanical properties, serum bone alkaline phosphatase (b-ALP), serum bone γ-carboxyglutamic acid-containing protein (BGP), serum bone morphogenetic protein-2 (BMP-2), serum tartrate-resistant acid phosphatase (TRACP) and serum carboxy terminal cross linked telopeptide of typeⅠcollagen (ICTP), bone mineral content (BMC) and bone structured histomorphometry. The protein and mRNA expression of TGF-β1, Smad2, Smad3, Smad4 and Smad7 were detected by Western blotting (WB) and quantitative real time polymerase chain reaction (qRT-PCR), respectively. ResultsAdministration of combined Herba Epimedii and Fructus Ligustri Lucidi decoction and combined active fractions could significantly prevent GC-induced bone loss by increasing the contents of serum b-ALP, BGP and BMP-2 as the markers of bone formation, reducing the serum TRACP and ICTP contents to inhibit bone resorption and enhancing BMC. They could also attenuate biomechanical properties and BMD reduction, deterioration of trabecular architecture in MO rats. The mRNA and protein expressions of TGF-β1, smad2, smad3 and smad4 were up-regulated, and the mRNA and protein expression of Smad7 was down-regulated following combined Herba Epimedii and Fructus Ligustri Lucidi treatment. ConclusionCombination of Herba Epimedii and Fructus Ligustri Lucidi exhibited protective effects on promoting bone formation and precluding bone resorption. The underlying mechanism may be attributed to its regulations on TGF-β1/Smads pathway. The substance bases of the combined herbs on anti-osteoporosis were total flavonoids of Herba Epimedii, total iridoids and flavonoids of Fructus Ligustri Lucidi.

Bone morphogenetic protein-2 will be a novel biochemical marker in urinary tract infections and stone formation

To investigate the role of bone morphogenetic protein-2 (BMP-2) in patients with urinary tract infection (UTI) and renal stone in relation to Tamm-Horsfall protein (THP) and osteopontin (OPN). ELISA kits were used to determine these markers in serum and urinary samples of 20 patients with UTI, 15 with renal stone and 10 controls. BMP-2 significantly increased in serum of patients who had UTI (P=0.05) and renal stone (P=0.01). In the case of UTI, serum BMP-2 at cutoff 44 pg/mL had sensitivity and specificity (92%, 80%), while cystatin C at cutoff 525 ng/mL showed sensitivity and specificity (85%, 91%). THP is a good predictor of renal diseases (P<0.001) by regression analysis. It is also the most sensitive urinary marker for UTI with sensitivity and specificity (94%, 75%) at cutoff 305 ng/mL. Combination of serum BMP-2 and cystatin C are more sensitive and accurate for early diagnosis of renal infection and damage.

Effect of Huogu II Formula (活骨II方) with medicinal guide Radix Achyranthis Bidentatae on bone marrow stem cells directional homing to necrosis area after osteonecrosis of the femoral head in rabbit

To investigate the effect of Huogu II Formula (II) with medicinal guide Radix Achyranthis Bidentatae (Ach) on bone marrow stem cells (BMSCs) homing to necrosis area after osteonecrosis of the femoral head (ONFH) frozen by liquid nitrogen in rabbit as well as to explore the mechanism of prevention and treatment for ONFH. The animal model of ONFH was established by liquid nitrogen frozen on the rabbit left hind leg. Forty-eight Japanese White rabbits were randomly assigned to sham-operated group, model group, Huogu II group, and Huogu II plus Ach group, with 12 rabbits in each. During the course of ONFH animal model establishment, all rabbits were subcutaneously injected with recombinant human granulocyte colony-stimulating factor [rhG-CSF, 30 μg/(kg·day) for continuous 7 days]. Meanwhile, normal saline and decoction of the two formulae were administrated by gavage, respectively. White blood cells (WBC) were counted in peripheral blood before and after injection of rhG-CSF. Materials were drawn on the 2nd and 4th weeks after model built; bone glutamine protein (BGP) and bone morphogenetic protein 2 (BMP2) levels in serum were tested. Histopathologic changes were observed by hematoxylin and eosin (HE) staining. BMP2 mRNA levels were detected with in situ hybridization (ISH) staining. 5-Bromo-2'-deoxyuridine (BrdU) and stromal cell derived factor 1 (SDF-1) were measured by immunohistochemical assay in femoral head of the left hind leg. Compared with the shamoperated group, the ratio of empty lacuna, serum BGP, and SDF-1 level in the model group increased significantly, and BMP2 in both serum and femoral head decreased significantly. However, in comparison with the model group, the empty lacuna ratio of Huogu II group and Huogu II plus Ach group decreased obviously in addition to the levels of serum BGP and BMP2, and the expressions of BMP2 mRNA, BrdU, and SDF-1 increased significantly. Above changes were particularly obvious in Huogu II plus Ach group. BGP and SDF-1 on the 2nd week and empty lacuna rate and serum BMP2 level on the 4th week in Huogu II group significantly exceeded their counterparts. On the 2nd week, only in Huogu II plus Ach group that the BrdU counting rose significantly. On the 4th week, empty lacuna rate and serum BMP2 level in Huogu II plus Ach group exceeded those in Huogu II group distinctively. To a certain extent, the medicinal guide Ach improves the preventive and therapeutic effects of Huogu II Formula on experimental ONFH model. The possible mechanism of this is related to its promoting effect on directional homing of BMSCs to the necrosis area.

Bone morphogenetic protein-2 levels are elevated in the patients with gastric cancer and correlate with disease progression

Bone morphogenetic protein-2 (BMP-2) was reported to enhance migration, invasion, and metastasis at the various types of cancer cells. The purpose of this study is to identify the role of BMP-2 in progression of gastric cancer. Forty-four patients with operable gastric cancer were enrolled. Also, twenty healthy volunteers were enrolled as control group. All patients received gastrectomy with D2 lymphadenectomy, and surgical staging was performed. Whole blood was obtained preoperatively in all patients, and serum BMP-2 levels were quantified by commercially available ELISA kit. Immunohistochemical stain for BMP-2 in all gastric cancer tissues was performed using tissue microarray. All patients showed increased serum BMP-2 levels compared with control group, when upper normal limit was defined as the mean of control serum level+2×standard deviation. The mean serum BMP-2 level of lymph node positive group was significantly elevated than that of lymph node-negative group (382.7 pg/ml, 95% CI 341.99-423.4 pg/ml vs 211.69 pg/ml, 95% CI 191.09-232.29 pg/ml, P<0.001). The serum BMP-2 was strongly correlated with the depth of invasion (T stage) and the extent of regional lymph node involvement (N stage) (r=0.662, P<0.001 and r=0.831, P<0.001, respectively). Moreover, the serum BMP-2 was correlated with the grade of tumor histology(r=0.421, P=0.008). Immunohistochemical stain showed the specific expression of BMP-2 in cancer cells compared with normal gastric mucosa. In conclusion, serum BMP-2 is associated with progression from early localized gastric cancer to locally advanced gastric cancer.

Optimized bone regeneration based on sustained release from three‐dimensional fibrous PLGA/HAp composite scaffolds loaded with BMP‐2

Contemporary treatment of critical bone defect remains a significant challenge in the field of orthopedic surgery. Engineered biomaterials combined with growth factors have emerged as a new treatment alternative in bone repair and regeneration. Our approach is to encapsulate bone morphogenetic protein-2 (BMP-2) into a polymeric matrix in different ways and characterize their individual performance in a nude mouse model. The main objective of this study is to examine whether the PLGA/HAp composite fibrous scaffolds loaded with BMP-2 through electrospinning can improve bone regeneration. The hypothesis is that different loading methods of BMP-2 and different HAp contents in scaffolds can alternate the release profiles of BMP-2 in vivo, therefore modify the performance of scaffolds in bone regeneration. Firstly, mechanical strength of scaffolds and HAp nanoparticles distribution in scaffolds were investigated. Secondly, nude mice experiments extended to 6 weeks were carried out to test the in vivo performance of these scaffolds, in which measurements, like serum BMP-2 concentration, ALP activity, X-ray qualification, and H&E/IHC tissue staining were utilized to monitor the growth of new bone and the changes of the corresponding biochemical parameters. The results showed that the PLGA/HAp composite scaffolds developed in this study exhibited good morphology/mechanical strength and HAp nanoparticles were homogeneously dispersed inside PLGA matrix. Results from the animal experiments indicate that the bioactivity of BMP-2 released from the fibrous PLGA/HAp composite scaffolds is well maintained, which further improves the formation of new bone and the healing of segmental defects in vivo. It is concluded that BMP-2 loaded PLGA/HAp composite scaffolds are promising for bone healing.

Enhancement of bone growth by sustained delivery of recombinant human bone morphogenetic protein-2 in a polymeric matrix.

The purpose of this study was to develop a polymeric sustained delivery system for recombinant human bone morphogenetic protein-2 (BMP-2) and to evaluate local bone growth induced by the sustained release of BMP-2 in an animal model. BMP-2 was incorporated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres to obtain different release rates. Two sustained and an immediate release implants were produced by suspending the BMP-2 loaded PLGA microspheres in aqueous sodium carboxymethylcellulose (CMC), lyophilizing, and cutting the dried materials to the size of the animal bone defects. The local in vivo release at the implantation site in rat calvarial defects was determined by gamma scintigraphy using radiolabeled BMP-2. The local bone induction in the critical size of rabbit calvarial defects was evaluated six weeks post implantation. The immediate release implant showed about 65% initial drug release within 24 h and the remaining BMP-2 quickly exhausted from the implantation site within 7 days. The sustained release implants, showing 45-55% initial release followed by a prolonged release for 21 days, released a greater amount of BMP-2 at the implantation site and maintained higher serum BMP-2 for the longer period of time compared to the immediate release implant. Significant bone growth was observed in all BMP-2 treated defects while the defects without treatment or with BMP-2-free implant showed minimal bone healing. 75-79% of rabbit calvarial defect area was healed with newly induced bone matrix by the sustained release implants in 6 weeks as compared to 45% recovery from the immediate release implant. The sustained delivery of BMP-2 based on the biodegradable PLGA microsphere system resulted in faster and more complete bone healing in the animal model.