Bone regeneration in critical-size defects of the mandible using biomechanically adapted CAD/CAM hybrid scaffolds: An in vivo study in miniature pigs.

The study aimed to analyze bone regeneration in critical-size defects using hybrid scaffolds biomechanically adapted to the specific defect and adding the growth factor rhBMP-2. For this animal study, ten minipigs underwent bilateral defects in the corpus mandibulae and were subsequently treated with novel cylindrical hybrid scaffolds. These scaffolds were designed digitally to suit the biomechanical requirements of the mandibular defect, utilizing finite element analysis. The scaffolds comprised zirconium dioxide-tricalcium phosphate (ZrO2-TCP) support struts and TCP foam ceramics. One scaffold in each animal was loaded with rhBMP-2 (100 µg/cm³), while the other served as an unloaded negative control. Fluorescent dyes were administered every 2 weeks, and computed tomography (CT) scans were conducted every 4 weeks. Euthanasia was performed after 3 months, and samples were collected for examination using micro-CT and histological evaluation of both hard and soft tissue. Intravital CT examinations revealed minor changes in radiographic density from 4 to 12 weeks postoperatively. In the group treated with rhBMP-2, radiographic density shifted from 2513 ± 128 (mean ± SD) to 2606 ± 115 Hounsfield units (HU), while the group without rhBMP-2 showed a change from 2430 ± 131 to 2601 ± 67 HU. Prior to implantation, the radiological density of samples measured 1508 ± 30 mg HA/cm³, whereas post-mortem densities were 1346 ± 71 mg HA/cm³ in the rhBMP-2 group and 1282 ± 91 mg HA/cm³ in the control group (p = 0.045), as indicated by micro-CT measurements. The histological assessment demonstrated successful ossification in all specimens. The newly formed bone area proportion was significantly greater in the rhBMP-2 group (48 ± 10%) compared with the control group without rhBMP-2 (42 ± 9%, p = 0.03). The mean area proportion of remaining TCP foam was 23 ± 8% with rhBMP-2 and 24 ± 10% without rhBMP-2. Successful bone regeneration was accomplished by implanting hybrid scaffolds into critical-size mandibular defects. Loading these scaffolds with rhBMP-2 led to enhanced bone regeneration and a uniform distribution of new bone formation within the hybrid scaffolds. Further studies are required to determine the adaptability of hybrid scaffolds for larger and potentially segmental defects in the maxillofacial region.

An effectiveness and economic analyses of tricalcium phosphate combined with iliac bone graft versus RhBMP-2 in single-level XLIF surgery in Thailand.

STUDY DESIGN: Retrospective study. OBJECTIVES: To perform effectiveness and economic analyses using data from a retrospective study of patients who underwent XLIF surgery using tricalcium phosphate combined with iliac bone graft (TCP + IBG) or BMP-2 in Thailand. METHODS: Data were collected from retrospective review of the medical charts and the spine registry of Siriraj Hospital, Bangkok, Thailand. The patients were divided into two groups (TCP + IBG group and BMP-2 group). Demographic, perioperative data, radiographic, clinical results, and quality of life related to health were collected and analyzed at 2-year follow-up. All economic data were collected during the perioperative period and presented as total charge, bone graft, implant/instrumentation, operative service, surgical supply, transfusion, medication, anesthesia, laboratory, and physical therapy. RESULTS: Twenty-five TCP + IBG and 30 BMP-2 patients with spondylolisthesis and spinal stenosis as primary diagnosis were included. There were no significant differences in all demographic parameters (gender, age, underlying disease, diagnosis, and level of spine) between these two groups. During the perioperative period, the TCP + IBG group had more mean blood loss and more postoperative complications compared to the BMP-2 group. At 2 years of follow-up, there were no significant differences between the radiographic and clinical outcomes of the TCP + IBG and BMP-2 groups. The fusion rate for TCP + IBG and BMP-2 at 2 years of follow-up was 80% and 96.7%, respectively, and no statistically significant differences were observed. All clinical outcomes (Utility, Oswestry Disability Index, and EuroQol Visual Analog Scale) at 2-year follow-up improved significantly compared to preoperative outcomes, but there were no significant differences between the TCP + IBG and BMP-2 groups, either at preoperatively or at 2-year follow-up. The total charge of TCP + IBG was statistically significantly lower than that of BMP-2. Furthermore, the charges of TCP + IBG and BMP-2 during the perioperative period in Thailand were up to three times less than those in the United States. CONCLUSIONS: Using TCP + IBG as a standalone bone substitution for XLIF surgery with additional posterior instrumentation resulted in significantly lower direct medical charge compared to those using BMP-2 in the perioperative period. However, we could not detect a difference in the long-term radiographic and clinical outcomes of patients with TCP + IBG and BMP-2. These suggest that TCP + IBG may be a valuable alterative bone graft, especially in low- and middle-income countries.

Current Trends in Recombinant Human Bone Morphogenetic Protein 2 (rhBMP2) Usage for Spinal Fusion Surgery.

(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.

The Use of Bone Morphogenetic Protein 2 (BMP-2) in Spine Surgery Is It Valuable?

BACKGROUND: Bone morphogenetic protein 2 (BMP-2) is one of the most widely used biologics in spine surgery. Its osteoinductive properties have been shown since its inception to improve fusion rates. Despite the positive effects on promoting fusion, there remains concerns regarding the significant costs associated with its use. The goal of this review was to investigate the value of BMP-2 in spine surgery. METHODS: A literature search was performed on various studies that report on the cost effectiveness and the value of BMP-2 in spine surgery. The value of BMP-2 was analyzed in two distinct settings: comparison to the gold standard iliac crest autograft and demineralized bone matrix. The value of BMP-2 was further analyzed in the setting of spinal deformity surgery. RESULTS: The findings of our review determined that BMP-2 offers significant improvement in outcomes related to improvement of fusion rates and minimization of pseudoarthrosis and reoperations related to pseudoarthrosis and donor site morbidity from harvesting iliac crest bone graft. However, BMP-2 has been found to be significantly more expensive in comparison to iliac crest bone graft and other bone graft substitutes, which detracts from its positive value. In deformity surgery, BMP-2 is associated with improvement in fusion rates as well as reducing the rate of reoperations and pseudoarthrosis. These positive outcomes, however, are associated with an expensive upfront cost for BMP-2. CONCLUSIONS: In terms of value, BMP-2 is associated with improvement in quality outcomes related to a reduction in pseudoarthrosis and reoperations. It also leads to improved outcomes with a reduction in donor site morbidity associated with iliac crest bone graft harvest. However, the value of BMP-2 is negatively affected because of its significant costs. As a result, higher expense thresholds are needed to increase quality adjusted life years in patients who receive BMP-2. Further research investigating ways to minimize the costs associated with BMP-2 use can further improve its value in spine surgery.

Concentration-Dependent Efficacy of Recombinant Human Bone Morphogenetic Protein-2 Using a HA/ß-TCP Hydrogel Carrier in a Mini-Pig Vertebral Oblique Lateral Interbody Fusion Model.

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.

Bone Morphogenetic Protein 2 Plus Leukocyte and Platelet-Rich Fibrin for the Treatment of MRONJ.

Leukocyte and platelet-rich fibrin is known to contain high concentrations of growth factors and when associated with rhBMP-2, it may increase bone remodeling due to its osteoinductive property. The aim of this case is to report the outcome of surgical treatment of medication-related osteonecrosis of the jaw with prototype plate installation and the use of leukocyte and platelet-rich fibrin in association with rhBMP-2 in a 78-year-old female patient under therapy with alendronate. The present Studies describes that the combination of this treatment presented complete healing of osteonecrosis and represents a promising treatment option to be used for medication-related osteonecrosis of the jaw.

Cefazolin/BMP-2-Loaded Mesoporous Silica Nanoparticles for the Repair of Open Fractures with Bone Defects.

The study aimed to explore the feasibility of a nanodrug delivery system to treat open fractures with bone defects. We developed a cefazolin (Cef)/bone morphogenetic protein 2 (BMP-2)@mesoporous silica nanoparticle (MSN) delivery system; meanwhile, Cef/MBP-2@ poly(lactic-co-glycolic acid) (PLGA) was also developed as control. For the purpose of determining the osteogenic and anti-inflammatory actions of the nanodelivery system, we cultured bone marrow mesenchymal stem cells (BMSCs) and constructed a bone defect mouse model to evaluate its clinical efficacy. After physicochemical property testing, we determined that MSN had good stability and did not easily accumulate or precipitate and it could effectively prolong the Cef's half-life by nearly eight times. In BMSCs, we found that compared with the PLGA delivery system, MSNs better penetrated into the bone tissue, thus effectively increasing BMSCs' proliferation and migration ability to facilitate bone defect repair. Furthermore, the MSN delivery system could improve BMSCs' mineralization indexes (alkaline phosphatase [ALP], osteocalcin [OCN], and collagen I [Col I]) to effectively improve its osteogenic ability. Moreover, the MSN delivery system could inhibit inflammation in bone defect mice, which was mainly reflected in its ability to reduce the release of IL-1ß and IL-4 and increase IL-10 levels; it could also effectively reduce apoptosis of CD4+ and CD8+ T cells, thus improving their immune function. Furthermore, the percentage of new bones, bone mineral density, trabecular volume, and trabecular numbers in the fracture region were improved in mice treated with MSN, which allowed better repair of bone defects. Hence, Cef/BMP-2@MSN may be feasible for open fractures with bone defects.

Effectiveness and Feasibility of Injectable Escherichia coli-Derived Recombinant Human Bone Morphogenetic Protein-2 for Anterior Lumbar Interbody Fusion at the Lumbosacral Junction in Adult Spinal Deformity Surgery: A Clinical Pilot Study.

OBJECTIVE: To explore the effectiveness and feasibility of injectable Escherichia coli-derived recombinant human bone morphogenetic protein-2 (injectable E-rhBMP-2, a combination of E. coli-derived recombinant human bone morphogenic protein-2 and a hydrogel type beta-tricalcium phosphate carrier) as a bone substitute for anterior lumbar interbody fusion (ALIF) of the lumbosacral junction in adult spinal deformity (ASD) patients. METHODS: A prospective single-institution therapeutic exploratory trial was conducted. Twenty patients (average age: 69.1 years; 19 female and one male; average fusion level: 7.95) diagnosed with ASD with sagittal imbalance who underwent surgical treatment including ALIF at the lumbosacral junction from December 2017 to January 2019 were evaluated. Injectable E-rhBMP-2 was prepared by dissolving 3 mg of E. coli-derived recombinant human bone morphogenetic protein-2 in 1.5 ml H2 O and mixing in situ with 9 g hydrogel type beta-tricalcium phosphate. This bone graft substitute was loaded onto a metal ALIF cage and L5 -S1 ALIF was performed in routine manner. Then posterior column osteotomy with multilevel oblique lumbar interbody fusion or pedicle subtraction osteotomy with accessory rod technique was performed to restore sagittal balance. Patients were followed up for 12 months. CT-based fusion rates were examined at 6 and 12 months after surgery. Also, clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale [VAS] score of the back and leg) were evaluated at 6 and 12 months after surgery. All postoperative adverse events were evaluated for the association with injectable E.BMP-2. RESULTS: Of the 20 patients, loss to follow-up occurred with one patient at 6 months after surgery and one patient at 12 months after surgery, resulting in a total of 18 patients who were available for follow-up. Six months after surgery, 68.4% patients achieved solid fusion. Twelve months after surgery, 100% fusion rate was achieved. Compared to baseline values, ODI scores improved to 45.8% and 63.7%, VAS (back) improved to 69.2% and 72.8%, and VAS (leg) improved to 49.2% and 64.8%, respectively, at 6 and 12 months after surgery (p < 0.001 for all). Ten cases of adverse events occurred. But no adverse events were associated with injectable E-rhBMP-2. CONCLUSION: Injectable E-rhBMP-2 will be an effective bone graft substitute when achieving solid interbody fusion in the lumbosacral junction.

Effectiveness of rhBMP-2 versus iliac autogenous bone graft in reconstructive surgery of cleft patients: an umbrella review.

The objective of this umbrella review was to determine the effectiveness of rhBMP-2 in the reconstructive surgery of cleft patients through an evaluation of bone filling and volume of newly formed bone in the cleft area. A systematic search was carried out in PubMed/ Medline, Scopus, Cochrane Database of Abstracts of Reviews of Effects (DARE), Latin American and Caribbean Health Sciences Literature (LILACS), and the System for Information on Grey Literature in Europe (SIGLE) via Open Grey, until June 2020. Risk of bias was assessed using the ROBIS tool. A total of 2739 articles were identified and, based on the inclusion and exclusion criteria, six were included for final evaluation. The bone filling rate was 74.23% in the rhBMP-2 group and 72.38% in the autogenous group. Regarding the risk of bias, none of the articles had a low risk, four had an uncertain risk, and two a high risk. The results of this umbrella review show that the studies had high and uncertain risks of bias, and high heterogeneity. There was a lack of evidence regarding the possible complications offered by this therapy. The recommendation to use BMP-2 for alveolar cleft reconstruction, especially in a paediatric population, should be viewed with caution. New primary studies are needed to assess this variable and safely determine the use of rhBMP-2 in reconstructive surgery for cleft patients.

The Rise and Fall of Bone Morphogenetic Protein 2 Throughout the United States.

STUDY DESIGN: Retrospective Database Study. OBJECTIVE: Investigate utilization of bone morphogenetic protein (BMP-2) between 2004 and 2014. SUMMARY OF BACKGROUND DATA: The utilization, particularly off-label utilization, of BMP-2 has been controversial and debated in the literature. Given the concerns regarding cancer and potential complications, the risk benefit profile of BMP must be weighed with each surgical case. The debate regarding the costs and potential side effects of BMP-2 compared with autologous iliac crest bone harvest has continued. METHODS: The National Inpatient Sample (NIS) database was queried for the use of BMP-2 (ICD-9-CM 84.52) between 2004 and 2014 across 44 states. The NIS database represents a 20% sample of discharges, weighted to provide national estimates. BMP-2 utilization rates in spine surgery fusion procedures were calculated as a fraction of the total number of thoracic, lumbar, and sacral spinal fusion surgeries performed each year. RESULTS: Between 2004 and 2014, BMP-2 was utilized in 927,275 spinal fusion surgeries. In 2004, BMP-2 was utilized in 28.3% of all cases (N=48,613). The relative use of BMP-2 in spine fusion surgeries peaked in 2008 at 47.0% (N=112,180). Since then, it has continued to steadily decline with an endpoint of 23.6% of cases in 2014 (N=60,863). CONCLUSIONS: Throughout the United States, the utilization of BMP-2 in thoracolumbar fusion surgeries increased from 28.3% to 47.0% between 2004 and 2008. However, from 2008 to 2014, the utilization of BMP-2 in thoracolumbar spine fusion surgeries decreased significantly from 47.0% to 23.4%. While this study provides information on the utilization of BMP-2 for the entire United States over an 11-year period, further research is needed to the determine the factors affecting these trends.

Off-label usage of RhBMP-2 in posterior cervical fusion is not associated with early increased complication rate and has similar clinical outcomes.

BACKGROUND CONTEXT: Arthrodesis is important for the success of posterior cervical fusion (PCF), however, there exists limited data regarding the safety and efficacy of bone morphogenic protein (BMP) in PCF. PURPOSE: The primary objective was to evaluate early postoperative complications associated with BMP in PCF and determine whether BMP leads to adverse early clinical outcomes. A secondary objective was to determine the optimal location for BMP sponge placement, within the facet joint (IF) or elsewhere, and the optimal dosage/level. DESIGN: Retrospective, consecutive case-control study. PATIENT SAMPLE: Seven hundred sixty-five patients who underwent PCF OUTCOME MEASURES: Patient-reported outcomes (PROs), complications, arthrodesis, optimum dose/level of BMP METHODS: Surgical data, including preoperative diagnosis, levels fused, type of bone graft, BMP dose (when used), and fusion technique were recorded. Complications were assessed by reviewing the medical record encompassing the first 6-weeks postoperative. These included medical, neurological, and wound-related complications and reoperation. Neurological complications were defined as any new weakness, radicular pain, or numbness. PROs were collected, including SF36, VAS, EQ-5D, and NDI scores. To determine the optimal dosage and location for BMP placement, a sub-analysis was performed. RESULTS: There were no significant differences between the BMP and no BMP group with regards to wound complications, neurological complications, or reoperation. There were no differences in PROs between BMP and no BMP. Placement of BMP for IF and at a dose of 0.87 mg/level minimized wound-related complications. The BMP group had a higher fusion rate compared to the no BMP group (96% vs. 91%, p=.02) when assessed 1 year post-operatively. CONCLUSION: BMP was not associated with a higher rate of early complications after PCF when the dose was minimized. Complications thought to be associated with BMP, such as compressive seroma, radiculitis, and wound-related complications were not seen at a higher rate. PROs at early follow-up were similar. Placement of BMP for IF and at lower doses than previously reported may minimize complications.

Use of Recombinant Human Bone Morphogenetic Protein-2 With Iliac Crest Bone Graft Instead of Iliac Crest Bone Graft Alone in Lumbar Spondylolysis.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to evaluate the clinical and radiographic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) in pars repair of lumbar spondylolysis. SUMMARY OF BACKGROUND DATA: BMP-2 is a growth factor that plays a role in the formation of bone and promotes bone healing. However, few studies of using rhBMP-2 in pars repair have been reported. METHODS: Direct pars repair and pedicle screw fixation was performed, which were added with 1 mg of rhBMP-2 and iliac crest bone graft in the study group (rhBMP-2 group, n=32) and iliac crest bone graft alone in the autograft group (n=36). Patients completed the visual analog scale and the Oswestry Disability Index preoperation, 3, 6, and 12 months after the operation. Computed tomography scans with axial and sagittal reconstructions were performed at 6, 9, 12, 18, and 24 months postoperatively. RESULTS: Baseline demographic data showed no significant difference between 2 groups. There were significant differences for the Oswestry Disability Index score at 3 and 6 months postoperatively, which were higher in the autograft group. There was no significant difference between the groups with respect to the overall union status. As for union speed, the trabecular bone appeared earlier and union rates were higher in rhBMP-2 group than in the autograft group at 9, and 12 months postoperatively. No complications were identified in either group. One case in the rhBMP-2 group and 2 cases in the autograft group underwent revision surgery. CONCLUSION: Compared with iliac crest bone graft alone, the use of rhBMP-2 can accelerate fusion in pars repair for young patients with spondylolysis. The union rates were significantly different at 9 and 12 months after surgery. This study showed no clinical difference when adding rhBMP-2 compared with iliac crest bone graft alone.

A Clinical Study on the Effect of Different Ratios of Recombinant Human Bone Morphogenetic Protein-2 Compound to Autogenous Bone on Cervical Interbody Fusion Based on Smart Healthcare.

With an increasing elderly population worldwide, the incidence of spine degenerative diseases with neck and shoulder pain as the main symptom is rising obviously, which has now become one of the important and difficult problems in sociomedical science. This study was to explore the effects of different ratios of recombinant human bone morphogenetic protein-2 (rhBMP-2) compound to the autogenous bone on cervical interbody fusion. 90 cervical degeneration patients with the need of surgical treatment admitted to our hospital from January 2019 to January 2020 were selected as the research objects and equally divided into group A, group B, and group C according to the order of admission, with 30 cases in each group and the ratios of rhBMP-2 compound to autogenous bone being 2 : 1, 1 : 1, and 1 : 2 respectively, and standard anterior cervical diskectomy and fusion (ACDF) treatment was performed to all patients to compare their surgery-related indexes, the Japanese Orthopaedic Association (JOA) score, the visual analog scale (VAS) score, the effect of cervical interbody fusion, and the postoperative complication rate (CR). Compared with group A and group C, group B achieved the significantly better surgery-related indexes (P < 0.05), significantly higher postoperative JOA scores (P < 0.05), significantly lower postoperative neck and upper limb VAS scores (P < 0.05), significantly better effect of cervical interbody fusion (P < 0.05), and significantly lower postoperative CR (P < 0.05). 1 : 1 is the best ratio of rhBMP-2 compound to the autogenous bone, for it can optimize patients' perioperative indexes, reduce the postoperative pain, lower the possibility of complications, and improve the effect of cervical interbody fusion, which should be promoted and applied in practice.

Mechanical Properties of Human Concentrated Growth Factor (CGF) Membrane and the CGF Graft with Bone Morphogenetic Protein-2 (BMP-2) onto Periosteum of the Skull of Nude Mice.

Concentrated growth factor (CGF) is 100% blood-derived, cross-linked fibrin glue with platelets and growth factors. Human CGF clot is transformed into membrane by a compression device, which has been widely used clinically. However, the mechanical properties of the CGF membranes have not been well characterized. The aims of this study were to measure the tensile strength of human CGF membrane and observe its behavior as a scaffold of BMP-2 in ectopic site over the skull. The tensile test of the full length was performed at the speed of 2mm/min. The CGF membrane (5 × 5 × 2 mm3) or the CGF/BMP-2 (1.0 µg) membrane was grafted onto the skull periosteum of nude mice (5-week-old, male), and harvested at 14 days after the graft. The appearance and size of the CGF membranes were almost same for 7 days by soaking at 4 °C in saline. The average values of the tensile strength at 0 day and 7 days were 0.24 MPa and 0.26 MPa, respectively. No significant differences of both the tensile strength and the elastic modulus were found among 0, 1, 3, and 7 days. Supra-periosteal bone induction was found at 14 days in the CGF/BMP-2, while the CGF alone did not induce bone. These results demonstrated that human CGF membrane could become a short-term, sticky fibrin scaffold for BMP-2, and might be preserved as auto-membranes for wound protection after the surgery.

A 24-month retrospective update: follow-up hospitalization charges and readmissions in US lumbar fusion surgeries using a cellular bone allograft (CBA) versus recombinant human bone morphogenetic protein-2 (rhBMP-2).

BACKGROUND: The objectives of this study were to build upon previously-reported 12-month findings by retrospectively comparing 24-month follow-up hospitalization charges and potentially-relevant readmissions in US lumbar fusion surgeries that employed either recombinant human bone morphogenetic protein-2 (rhBMP-2) or a cellular bone allograft comprised of viable lineage-committed bone cells (V-CBA) via a nationwide healthcare system database. METHODS: A total of 16,172 patients underwent lumbar fusion surgery using V-CBA or rhBMP-2 in the original study, of whom 3,792 patients (23.4%) were identified in the current study with all-cause readmissions during the 24-month follow-up period. Confounding baseline patient, procedure, and hospital characteristics found in the original study were used to adjust multivariate regression models comparing differences in 24-month follow-up hospitalization charges (in 2020 US dollars) and lengths of stay (LOS; in days) between the groups. Differences in potentially-relevant follow-up readmissions were also compared, and all analyses were repeated in the subset of patients who only received treatment at a single level of the spine. RESULTS: The adjusted cumulative mean 24-month follow-up hospitalization charges in the full cohort were significantly lower in the V-CBA group ($99,087) versus the rhBMP-2 group ($124,389; P < 0.0001), and this pattern remained in the single-level cohort (V-CBA = $104,906 vs rhBMP-2 = $125,311; P = 0.0006). There were no differences between groups in adjusted cumulative mean LOS in either cohort. Differences in the rates of follow-up readmissions aligned with baseline comorbidities originally reported for the initial procedure. Subsequent lumbar fusion rates were significantly lower for V-CBA patients in the full cohort (10.12% vs 12.00%; P = 0.0002) and similar between groups in the single-level cohort, in spite of V-CBA patients having significantly higher rates of baseline comorbidities that could negatively impact clinical outcomes, including bony fusion. CONCLUSIONS: The results of this study suggest that use of V-CBA for lumbar fusion surgeries performed in the US is associated with substantially lower 24-month follow-up hospitalization charges versus rhBMP-2, with both exhibiting similar rates of subsequent lumbar fusion procedures and potentially-relevant readmissions.

Evaluating the efficacy of recombinant human bone morphogenic protein-2 in the treatment of alveolar clefts with autologous bone grafting using computer-aided engineering techniques.

Recent studies have indicated the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) to be a viable adjunctive to alveolar cleft reconstruction owing to its osteoinductive capacity. This study aimed to evaluate the efficacy of rhBMP-2 in the treatment of alveolar cleft with autologous bone grafts by precise volumetric analysis. Twenty-six patients (aged 8-14) with unilateral alveolar clefts were enrolled in this comparative study. Patients were divided into two groups: the iliac crest bone graft (ICBG) was placed at the side of the cleft in the control group (ICBG group), and rhBMP-2 was mixed with the ICBG in the rhBMP-2 group (BMP group). Helical computed tomographic images were obtained preoperatively and 12 months postoperatively. The datasets were reconstructed as three-dimensional (3D) images using Mimics software and processed using Geomagic Wrap. The newly formed bone of the alveolar cleft was segmented by identifying the differences between preoperative and postoperative 3D images. In the ICBG group, the volume of newly formed bone ranged from 0.25 to 0.88 cm3, and the mean (SD) bone formation percentage was 42.01% (15.57%). In the BMP group, the volume of newly formed bone ranged from 0.34 to 1.09 cm3, and the bone formation mean (SD) percentage was 55.79% (11.84%). There was a statistically significant difference between the two groups in terms of the postoperative percentage of bone formation (p = 0.022). Thus, rhBMP-2 combined with an autologous bone graft is a promising technique to improve the results of secondary alveolar bone grafting.

Programmed Multidrug Delivery Based on Bio-Inspired Capsule-Integrated Nanocoatings for Infected Bone Defect Treatment.

Infection and delayed wound healing are two major serious complications related to traumatic injuries and cause a significant burden to patients and society. Most currently available drug delivery materials typically carry a single drug, lack protection from drug loading, and face challenges in on-demand and precisely controlled drug release. Here, we report a flower (Cirsium arvense)-inspired capsule-integrated multilayer nanofilm (FICIF), synthesized using a layer-by-layer self-assembly, for programmed multiple drug co-delivery for trauma (open fracture as an example) treatments. Our approach allows polypeptide multilayer nanofilms and innovative impregnated capsules to assemble hierarchical reservoirs with specific drug binding sites, shielding protection capability, and ordered packing structures. The resultant FICIF nanocarriers enable sustained and on-demand co-delivery of a unique immune-tuning cytokine (interleukin 12p70) and a growth factor (bone morphogenetic protein 2) in clinical use, resulting in extraordinary anti-infection (3 orders of magnitude improved bacterial killing) and bone regeneration (5 times enhanced bone healing) in treating infected rat femur fractures. The successful synthesis of these biomimetic high-performance delivery nanocoatings is expected to serve as a source of inspiration for the development of biomaterials for various clinical applications.

Effectiveness of Bone Graft for an Alveolar Defect on Adjacent Second Molar After Impacted Mandibular Third Molar Extraction.

PURPOSE: This retrospective study examined distal bone healing on the adjacent second molar between the demineralized bone matrix incorporated with recombinant human bone morphogenetic protein-2 (DBM/rhBMP-2) and a collagen sponge in the mandibular third molar extraction socket. MATERIALS AND METHODS: From 2018 to 2020, 26 extraction patients (male, average 21.5 years), who received a graft (each of 13 using DBM/rhBMP-2 and collagen plug, respectively) on the extraction socket without primary closure, were enrolled in this study. The bony defect was measured by computed tomography before and 6 months after the extraction. The difference in the bone healing was analyzed between the DBM/rhBMP-2 and collagen plug groups using a Mann-Whitney U test. RESULTS: No complications, such as infection and food packing, were encountered. The DBM/rhBMP-2 and collagen plug groups showed a similar distribution of preoperative bony defect (median 5.8 and 5.0 mm, respectively). After 6 months, more bone healing was observed in the DBM/rhBMP-2 group than in the collagen plug group (median 3.85 and 2.37 mm, respectively, P = .029) CONCLUSIONS: A DBM/rhBMP-2 graft after a third molar extraction does significantly alter the bony defect on the distal aspect of the second molar compared with a collagen plug.

LINC00968 promotes osteogenic differentiation in vitro and bone formation in vivo via regulation of miR-3658/RUNX2.

Osteogenic differentiation of dental pulp stem cells (DPSCs) is considered as a promising strategy in posterior maxilla tooth implantation. Information on the function and mechanisms of long non-coding RNAs (lncRNAs) in osteogenic differentiation of DPSCs is growing, however, the mechanism of LINC00968 and miR-3658 in regulating osteogenic differentiation of DPSCs still needs to be explored. In this study, the LINC00968 and miR-3658 expression level was upregulated and downregulated in DPSCs and peri-implantitis DPSCs (pDPSCs) treated with bone morphogenic protein (BMP)2, respectively. Moreover, the effects of LINC00968 and miR-3658 on BMP2-induced osteogenic differentiation of DPSCs in vitro using Alizarin Red S staining, alkaline phosphatase (ALP) activity, quantitative real time PCR and Western blot assays showed that overexpression of LINC00968 significantly promoted mineralized bone matrix, alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and osterix (OSX) expression levels for osteogenic differentiation of DPSCs and pDPSCs; and overexpression of miR-3658 showed an opposite result that inhibited osteogenic differentiation of DPSCs and pDPSCs. Luciferase reporter assay showed that luciferase activities of LINC00968-WT reporter and RUNX2-WT reporter were strongly suppressed by miR-3658 overexpression. In addition, the miR-3658 upregulation interfered ectopic bone formation in vivo stimulated by LINC00968. In general, we had identified a novel molecular pathway involving LINC00968/miR-3658/RUNX2 during DPSCs and pDPSCs differentiation into osteoblasts, which might facilitate bone anabolism.