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The treatment of bone defects with recombinant bone morphogenetic protein‐2 (BMP‐2) requires high doses precluding broad clinical application. Here, a bioengineering approach is presented that strongly improves low‐dose BMP‐2‐based bone regeneration by mobilizing healing‐associated mesenchymal progenitor cells (MPCs). Smart synthetic hydrogels are used to trap and study endogenous MPCs trafficking to bone defects. Hydrogel‐trapped and prospectively isolated MPCs differentiate into multiple lineages in vitro and form bone in vivo. In vitro screenings reveal that platelet‐derived growth factor BB (PDGF‐BB) strongly recruits prospective MPCs making it a promising candidate for the engineering of hydrogels that enrich endogenous MPCs in vivo. However, PDGF‐BB inhibits BMP‐2‐mediated osteogenesis both in vitro and in vivo. In contrast, smart two‐way dynamic release hydrogels with fast‐release of PDGF‐BB and sustained delivery of BMP‐2 beneficially promote the healing of bone defects. Collectively, it is shown that modulating the dynamics of endogenous progenitor cells in vivo by smart synthetic hydrogels significantly improves bone healing and holds great potential for other advanced applications in regenerative medicine. [ABSTRACT FROM AUTHOR]

Standardized and reproducible animal models are required for the assessment of bone healing mediated by biomaterials, cells, and drugs. Among the available bone‐fractured models, calvarial defect is a simple and adequate option when researchers investigate intra‐membranous bone formation and the influence of their regenerative solutions. However, the conventional surgical tools required to perform calvaria osteotomies (i.e., trephine bur mounted on a dental handpiece, DS) can affect the subjacent tissues of the skull, which are the dura mater and the brain. We hypothesized that the quality of the calvaria defect and the preservation of underlying tissues can be improved using a novel Anspach high‐speed drill with a Codman Neuro Disposable Perforator handheld (ACP). Using a rabbit cadaveric models, we performed calvarial defects with either conventional DS or the ACP system, and showed that both techniques allowed to create standardized defects with circular geometry. We demonstrated that the ACP had clear benefices in terms of DM preservation and absence of exothermic reaction upon drilling. Even though this comparative work was conducted on cadaver, it is of substantial importance as it introduces a novel technique, easily applicable to investigate calvaria bone healing, which brings clear advantages compared to the conventional dental station. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1–9, 2019. [ABSTRACT FROM AUTHOR]

Objectives To test whether or not chemical and/or physical modifications of polyethylene glycol ( PEG) hydrogels influence degradation time, matrix/membrane stability, and integration into surrounding hard and soft tissues. Material and methods In 28 rabbits, six treatment modalities were randomly applied to six sites on the rabbit skull: a dense network PEG hydrogel ( PEG HD), a medium-dense network PEG hydrogel ( PEG MD), a medium-dense network PEG hydrogel modified with an RGD sequence ( PEG MD/ RGD), a medium-dense network PEG hydrogel modified with RGD with reduced carboxymethyl cellulose ( PEG MD/ RGD_ LV), a loose network PEG hydrogel modified with RGD ( PEG LD/ RGD), and a collagen membrane ( BG). Descriptive histology and histomorphometry were performed at 1, 2, 4, and 6 weeks. Results PEG HD revealed the highest percentage of residual matrix at all time points starting with 47.2% (95% CI: 32.8-63.8%) at 1 week and ending with 23.4% (95% CI: 10.3-49.8%) at 6 weeks. The hydrogel with the loosest network ( PEG LD/ RGD) was stable the first 2 weeks and then degraded continuously with a final area of 8.3% (95% CI: 3.2-21.2%). PEG HD was the most stable and densely stained membrane, whereas PEG MD and PEG LD matrices integrated faster, but started to degrade to a higher degree between 2 and 4 weeks. PEG MD degradation was dependent on the addition of RGD and the amount of CMC. Conclusions Chemical and/or physical modifications of PEG hydrogels influenced matrix stability. PEG MD/ RGD demonstrated an optimal balance between degradation time and integration into the surrounding soft and hard tissues. [ABSTRACT FROM AUTHOR]

ABSTRACT Intervertebral disc (IVD) degeneration is the leading trigger of low back pain, which causes disability and leads to enormous healthcare toll worldwide. Biological treatment with growth factors has evolved as potential therapy for IVD regeneration. Bone morphogenetic protein 2 (BMP-2) and BMP-7 have shown promise in this regard. In the current study, we evaluated the effect of BMP-2/7 heterodimer for disc regeneration both in vitro and in organ culture. Nucleus pulposus (NP) cells isolated from bovine caudal disc were cultured in a fibrin-hyaluronan (FBG-HA) hydrogel for up to 14 days. BMP-2/7 heterodimer covalently incorporated within the hydrogel up-regulated the aggrecan and type II collagen gene expression, and glycosaminoglycan synthesis of NP cells. The activity of the BMP-2/7 heterodimer was dose dependent. The higher dose of BMP-2/7 was further assessed in an IVD whole organ system. After 14 days of culture with cyclic dynamic load, the BMP-2/7 heterodimer delivered into the nucleotomized region showed potential to stimulate the gene expression and synthesis of proteoglycan in the remaining NP tissue after partial nucleotomy. The gene expression level of type I collagen and alkaline phosphatase in the native disc tissue were not affected by BMP-2/7 treatment, indicating no adverse fibroblastic or osteogenic effect on the disc tissue. Intradiscal delivery of BMP-2/7 heterodimer may be a promising therapeutic approach for NP regeneration. The current IVD whole organ partial nucleotomy model may be utilized for screening of other biomaterials or drugs to treat early degenerative disc disorders. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:51-60, 2017. [ABSTRACT FROM AUTHOR]

Aim To test whether or not the network structure and the addition of recombinant human platelet-derived growth factor- BB (rh PDGF- BB) to a chemically cross-linked collagen matrix ( CCM)- and a non-cross-linked collagen matrix ( NCCM)-influenced tissue integration, angiogenesis, and matrix degradation. Materials and methods Four treatment modalities were randomly assigned to four unconnected pouches in the back of 50 rats: (i) CCM- S (soaked in saline), (ii) CCM- P (plus rh PDGF- BB), (iii) NCCM- S (soaked in saline), and (iv) NCCM- P (plus rh PDGF- BB). The animals were sacrificed at 2, 4, 8, 16, and 24 weeks. Descriptive histology and histomorphometric assessments were performed thereby evaluating matrix thickness, the number of vessels (angiogenesis), and connective tissue formation. Means and standard deviations were calculated. Robust linear mixed modeling was used to test the effect of group ( NCCM vs CCM), rh PDGF- BB, and time point of sacrifice (2, 4, and 8 weeks). Results The thickness of NCCM groups revealed stability (range 440-570 μm) over 8 weeks, while the matrices were no longer present at 16 and 24 weeks. CCM matrices demonstrated a maximal thickness at 2 weeks (2689 ± 187 μm for CCM- S and 2693 ± 389 μm for CCM- P), a decrease of roughly 40% at 8 weeks, but were still present at 16 and 24 weeks. Vascularization of NCCM gradually increased over time with a peak (mean 17.0; SD 1.7) for NCCM-S and NCCM- P (22.0 ± 34.8) at 8 weeks. Angiogenesis in CCM was significantly more pronounced at early time points with a peak at 2 weeks (29.3 ± 16.8 for CCM- S and 30.3 ± 18.4 for CCM- P). No statistically significant effect of rh PDGF- BB was observed for any of the evaluated parameters (all P > 0.05). Conclusions The compact layer (in NCCM) delayed angiogenesis and connective tissue formation, while the spongeous cross-linked matrix of CCM facilitated early vascularization and demonstrated network presence over a longer time span. [ABSTRACT FROM AUTHOR]

Bone morphogenetic proteins (BMPs) are deposited in bone and responsible for osteoinduction. The interplay between delivery system and BMP, resulting in a characteristic release profile, is crucial for clinical success. We here report on two apatite based commercially available granules which could potentially be used in a combination product with recombinant human BMP-2 (rhBMP-2). Regardless of their similar chemistry, their interaction with rhBMP-2 differs. Deproteinized bovine bone matrix (DBBM), a clinically well-established bone substitute, has a high affinity to rhBMP-2 and releases only 50% of the growth factor during the first 2 weeks in vitro. Activity of the physio-adsorbed rhBMP-2 is indicated by an enhanced bone augmentation in vivo. In contrast, all rhBMP-2 delivered in combination with synthetic hydroxyapatite/β-tricalcium phosphate (HA/TCP) granules is released during the first 24 h. For both HA/TCP and DBBM, the released rhBMP-2 is active in vitro. Our results suggest that the different release behavior from these two apatite granules is due to the 1000-fold higher specific surface area of DBBM compared to HA/TCP. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 628-638, 2015. [ABSTRACT FROM AUTHOR]

Objectives To compare the clinical and histological outcomes of a resorbable modified polylactide/polyglycolide acid (PLGA) test membrane and a titanium-reinforced expanded polytetrafluorethylene (ePTFE) control membrane used for guided bone regeneration (GBR) around dental implants. Materials and methods A total of 40 patients with peri-implant dehiscence-type defects were randomly allocated to a GBR procedure using either a modified PLGA test or an ePTFE control membrane. Soft tissue condition, implant integration, adverse events and quality of life were recorded during the 6-month healing period. At re-entry peri-implant bone defect dimensions were measured and compared with values recorded at implant/GBR surgery. A biopsy was retrieved for qualitative and quantitative histological analyses. A comparison between the groups was conducted using non-parametric statistical tests. Results Soft tissue complications were observed in five test patients and two control patients. Except for soft tissue complications and incomplete regeneration, no procedure- or device-related adverse events were observed. The vertical bone defect component was, in mean, reduced by−5.1 mm (95% CI −6.8, −3.3) in the test group and −6.9 mm (95% CI −8.2, −5.5 mm) in the control group. The mean residual vertical defect height measured 1.2 ± 2.4 mm in the test group and 0.3 ± 1.1 mm in the control group meaning a mean defect resolution of 81% in the test group and 96% in the control group ( P = 0.161). The horizontal bone thickness at implant shoulder level decreased from a mean of 3.2 mm to 1.4 mm (−56%, mean −1.7 mm, 95% CI −2.3, −1.1) in the test group and from 3.3 mm to 2.5 mm (−24%, mean −0.8 mm, 95% CI −1.3, −0.3) in the control group ( P = 0.022). Qualitative and quantitative histological analyses did not show significant differences in the tissue composition between groups. Conclusion Peri-implant GBR was successfully performed using either of the membranes. The control membrane was able to better maintain the horizontal thickness of regenerated bone and revealed less soft tissue complications. No statistically valid evidence about the superiority of one membrane was found in any other parameters. Soft tissue dehiscences occur with both types of membranes and can impair the amount of regenerated bone. [ABSTRACT FROM AUTHOR]

Bioengineered bone substitutes might represent alternatives to autologous bone grafts in medically compromised patients due to reduced operation time and comorbidity. Due to the lack of an inherent vascular system their dimension is limited to the size of critical bone size defect. To overcome this shortcoming, the experiment tried to create heterotopic bone around vessels. In vivo, a two-component fibrin and thrombin gel containing recombinant bone morphogenic protein (rhBMP-2) and transglutamate vascular endothelial growth factor (TG-VEGF) in different ratios, respectively, was injected into a dimensionally stable membrane tube, wrapped around the femoral vessel bundle in twelve New Zealand white rabbits. Sacrifice occurred eight weeks postoperatively. Microcomputed tomography of the specimens showed significantly increased bone volume in the rhBMP-2 to TG-VEGF ratio of 10 to 1 group. Histology showed new bone formation in close proximity to the vessel bundle. Immunohistochemistry detected increased angiogenesis within the newly formed bone in the rhBMP-2 to TG-VEGF ratios of 3 to 1 and 5 to 1. Heterotopic bone was engineered in vivo around vessels using different rhBMP-2 and TG-VEGF ratios in a fibrin matrix injected into a dimensionally stable membrane tube which prevented direct contact with skeletal muscles. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present study was to compare a newly developed biodegradable polylactide/polyglycolide/N‐methyl‐2‐pyrrolidone (PLGA/NMP) membrane with a standard resorbable collagen membrane (RCM) in combination with and without the use of a bone substitute material (deproteinized bovine bone mineral [DBBM]) looking at the proposed tenting effect and bone regeneration. Materials and methods: In five adult German sheepdogs, the mandibular premolars P2, P3, P4, and the molar M1 were bilaterally extracted creating two bony defects on each site. A total of 20 dental implants were inserted and allocated to four different treatment modalities within each dog: PLGA/NMP membrane only (Test 1), PLGA/NMP membrane with DBBM (Test 2), RCM only (negative control), and RCM with DBBM (positive control). A histomorphometric analysis was performed 12 weeks after implantation. For statistical analysis, a Friedman test and subsequently a Wilcoxon signed ranks test were applied. Results: In four out of five PLGA/NMP membrane‐treated defects, the membranes had broken into pieces without the support of DBBM. This led to a worse outcome than in the RCM group. In combination with DBBM, both membranes revealed similar amounts of area of bone regeneration and bone‐to‐implant contact without significant differences. On the level of the third implant thread, the PLGA/NMP membrane induced more horizontal bone formation beyond the graft than the RCM. Conclusion: The newly developed PLGA/NMP membrane performs equally well as the RCM when applied in combination with DBBM. Without bone substitute material, the PLGA/NMP membrane performed worse than the RCM in challenging defects, and therefore, a combination with a bone substitute material is recommended. To cite this article: 
Jung RE, Kokovic V, Jurisic M, Yaman D, Subramani K, Weber FE. Guided bone regeneration with a synthetic biodegradable membrane: a comparative study in dogs.
Clin. Oral Impl. Res. 22, 2011; 802–807
doi: 10.1111/j.1600‐0501.2010.02068.x [ABSTRACT FROM AUTHOR]

The aim of the present study was to test whether the delivery of enamel matrix derivate (EMD) via synthetic polyethylene glycol (PEG)-based hydrogels with and without RGD sequences enhances bone formation in vivo. In each of 10 rabbits, four titanium cylinders were placed on the external cortical bones of their calvaria. The following four treatment modalities were randomly allocated: One of the four cylinders was left empty (control), the other three were filled with a combination of PEG matrix with hydroxyapatite/tricalciumphosphate (HA/TCP) granules and EMD in a concentration of 100 μg/ml (test 1) or 500 μg/ml (test 2) or 500 μg/ml and RGD peptide (test 3). After 8 weeks, the animals were sacrificed and ground sections were obtained for histological analysis. For statistical analysis, the Kruskal-Wallis test was applied ( P<0.05). The histomorphometric analysis revealed a statistically larger area fraction of newly formed bone in the EMD 500/RGD group (54.8±14.5%) compared with the control group (28.7±10.3%) and the EMD 500 group (31.2±14.1%) and non-significantly higher area fraction compared with the EMD 100 group (38.2±10.4%). The percentage of mineralized bone showed no statistically significant differences among the four groups. The mean percentage of mineralized bone was 13.6±3.3% in the control group, 14.2±5.8% in the EMD 100 group, 11.69±5.9% in the EMD 500 group and 15.66±5.2% in the EMD 500/RGD group. No statistically significant difference regarding the bone-to-graft contact between the EMD 100 group (23±15.7%), the EMD 500 group (22.2±14.6%) and the EMD 500/RGD group (21.6±8.8%) was observed. The combination of a PEG matrix containing EMD with HA/TCP granules had no effect on the formation of mineralized bone tissue in rabbit calvaria. The addition of RGD peptide to the PEG/EMD 500 combination increased the area fraction of newly formed bone compared with the other treatment groups. Further studies are indicated to study a possible synergistic effect of EMD and RGD. Schneider D, Weber FE, Hämmerle CHF, Feloutzis A, Jung RE. Bone regeneration using a synthetic matrix containing enamel matrix derivate Clin. Oral Impl. Res, 2011; 214-222. doi: 10.1111/j.1600-0501.2010.01985.x [ABSTRACT FROM AUTHOR]

Objectives: To compare the performance and safety of Inion GTR™ Biodegradable Membrane System and Geistlich resorbable bilayer Bio-Gide® membrane in human bone regeneration. Material and methods: In a multicenter, split blind, comparative, randomized, prospective, pilot study 15 patients have been randomized at surgery whether to be treated either with Inion GTR™ Biodegradable Membrane System on one and Geistlich resorbable bilayer Bio-Gide® membrane on the other side or vice versa after surgical removal of both fully impacted wisdom teeth. During the follow-up visits at week 1, 2 and 6 and at months 3 and 6 the general state, the wound, eventual adverse events and the medication of the patients were assessed. Computed Tomography (CT) scans were performed immediately and 3 months after the surgery, before biopsy collection. Semi-quantitative histological evaluation and histomorphometric analyses were performed according to the ISO 10993-6 standard. New bone formation and membrane integration were evaluated by CT scan measurements. Tissue healing was evaluated clinically and by photographs between the time on teeth extraction and during follow ups. Results: Five patients were smokers, none drank alcohol. Mild adverse events like wound infection, haematoma or late swelling of the gums occurred in three patients. The trephine bur harvest of bone biopsies under local anaesthesia was uneventful. Whereas specimens from the sites treated with the Inion membrane yielded 17.0% (SD 24%), the Bio-Gide membrane sites yielded 13.5% (SD 15%) of bone tissue density. In sites treated with the Inion membrane, 9.5% of old bone density and 7.5% of newly formed bone could be found, whereas the Bio-Gide® membrane sites showed 3.8% of old bone density and 9.8% of newly formed bone. There were no statistically significant differences between the two groups with respect to the two variables. The osteoid rim was more extended with the Bio-Gide® (6.6 mm) than with the Inion membrane (5.1 mm) but the difference between the two treatments did not reach statistical significance. Highly significant reductions in the area of the defect with both membranes were detected with significant increases in CT density at the immediate inferio–buccal adjacent bone and in the surgical defect area with both membranes. However, there was neither significant change in CT density in the immediate inferior–lingual adjacent bone of the two membranes, nor significant difference between the membranes on any of the four measurements (area of defect: P=0.1354; CT density immediate inferio–buccal adjacent bone: P=0.7615; CT density surgical defect area: P=0.1876; CT density immediate inferio–lingual adjacent bone: P=0.4212). Conclusion: The overall clinical outcome was satisfying and the majority of the patients showed an uneventful healing phase. Both membranes presented similar capacities regarding their barrier function and were associated with analogous bone regeneration. No statistically valid evidence about the superiority of one particular membrane was obtained. For the patient the only difference is that one product is animal derived and the other synthetic. [ABSTRACT FROM AUTHOR]

Objective: The aim of this randomized-controlled clinical trial was to evaluate the long-term outcome of implants placed in bone augmented with a xenogenic bone substitute material and a collagen membrane with or without the addition of recombinant human bone morphogenetic protein-2 (rhBMP-2). Material and methods: Eleven patients received a total of 34 implants placed into sites exhibiting lateral bone defects. In a split mouth design, the defects were randomly treated with the graft material and the collagen membrane either with (test) or without (control) rhBMP-2. The patients were examined 3 and 5 years after insertion of the prosthetic restoration. Student's paired t-test was performed to detect differences between the two groups. Results: The survival rate at 3 and 5 years was 100% for both groups. The peri-implant soft tissues were stable and healthy without any difference between the two groups. The prosthetic reevaluation demonstrated four loose prosthetic screws during the first 3 years and seven ceramic chippings after 3 and 5 years. The mean distance between the first bone to implant contact to implant abutment junction at 3 years was 1.37 mm (test), 1.22 mm (control), and 1.38 mm (test), and 1.23 mm (control) at 5 years. The difference of <0.2 mm between test and control implants was not statistically significant. The mean change of the marginal bone level between baseline and 5 years ranged from −0.07 mm (mesial, test), −0.11 mm (distal, test), −0.03 mm (mesial, control), to +0.13 mm (distal, control). No statistically significant differences were observed between test and control sites. Conclusion: Implants placed in bone augmented with and without rhBMP-2 revealed excellent clinical and radiological outcomes after 3 and 5 years. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to test whether or not a synthetic matrix consisting of a polyethylene glycol (PEG) hydrogel containing recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with grafting materials enhances bone regeneration compared with grafting alone or empty control sites. Material and methods: In each of 10 rabbits, four titanium cylinders were screwed in perforated slits made in the external cortical bones of the calvaria. The following four treatment modalities were randomly allocated: (1) empty control, (2) a combination of a PEG matrix and hydroxyapatite/tricalciumphosphate (HA/TCP) granules and a combination of a PEG matrix containing either 10 μg/ml (3) or 30 μg/ml (4) of BMP-2 and HA/TCP granules. After 8 weeks, the animals were sacrificed and ground sections were obtained for histological analysis. For statistical analysis repeated measures ANOVA and subsequent pairwise Student's t-test were applied ( P<0.01). Results: Histomorphometric analysis showed an average area fraction of newly formed bone of 13.96±5.98% for the empty control, 15.16±7.95% for the PEG and HA/TCP group, 26.32±8.56% for the group containing 10 μg rhBMP-2/ml, and 30.15±7.63% for the group containing 30 μg rhBMP-2/ml. Statistical analysis revealed significantly more newly formed bone in the two rhBMP-2 groups compared with the PEG and HA/TCP group and with the empty control. Regarding the surface fraction of the HA/TCP graft particles covered with newly formed bone the addition of rhBMP-2 revealed a more than two-fold increase compared with cylinders containing HA/TCP granules without rhBMP-2. This difference reached statistical significance. Conclusions: It is concluded that rhBMP-2 significantly enhances bone regeneration in rabbits when delivered by a synthetic matrix containing HA/TCP. This synthetic PEG matrix containing HA/TCP granules apparently fulfills a number of criteria required for an ideal carrier system for rhBMP-2. [ABSTRACT FROM AUTHOR]

The aim of the present study was to test whether or not the application of an in situ formed synthetic hydrogel made of polyethylene glycol (PEG) used as a biodegradable membrane for guided bone regeneration will result in the same amount of bone regeneration as with the use of an expanded polytetrafluoro-ethylene (ePTFE) membrane. In eight New Zealand White rabbits, four evenly distributed 6 mm diameter defects were drilled into the calvarial bone. Three treatment modalities were evenly distributed among the 32 defects: hydroxyapatite (HA)/tricalciumphosphate (TCP) granules covered at the outer and inner surface with a PEG membrane (test), HA/TCP granules covered at the outer and inner surface with an ePTFE membrane (positive control) and HA/TCP granules alone without membranes (negative control). After 4 weeks, the animals were sacrificed and the calvarial bones were removed. The area fraction of newly formed bone was determined by histomorphometrical analysis of the vertical sections from the middle of the defect and by micro-computed tomography of the entire defect. Multiple regression analysis (SAS® GLM) was used to model the amount of new bone formation. The quantitative histomorphometric analysis clearly revealed higher values of newly formed bone for the two membrane groups compared with the negative control group. The average area fractions of newly formed bone measured within the former defect amounted to 20.3±9.5% for the PEG membrane, 18.9±9.9% for the ePTFE membrane, and 7.3±5.3% for the sites with no membrane. The micro-computed tomography also showed higher values of new bone formation for the PEG and for the ePTFE groups compared with the negative control group. The GLM revealed a highly significant effect of the treatment on the amount of bone formation ( P=0.0048). The values for the negative control group were significantly lower than the ones found in the PEG membrane group ( P=0.0017), whereas the ePTFE membrane group showed no significant difference from the PEG membrane group. It is concluded that the PEG membrane can be used successfully as a biodegradable barrier membrane in the treatment of non-critical-size defects in the rabbit skull, and leads to similar amounts of bone regeneration as an ePTFE membrane. [ABSTRACT FROM AUTHOR]

Copyright of Clinical Oral Implants Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A novel form of recombinant human bone morphogenetic protein-2 (BMP-2) was explored for effective incorporation and long-term retention into fibrin ingrowth matrices. The solubility of native BMP-2 is greatly dependent on its glycosylation. To enhance retention of BMP-2 in fibrin matrices, a nonglycosylated form (nglBMP-2), which is less soluble than the native glycosylated protein, was produced recombinantly and evaluated in critical-size defects in the rat calvarium (group n=6). When 1 or 20 μg nglBMP-2 was incorporated by precipitation within the matrix, 74 ± 4% and 98 ± 2% healing was observed in the rat calvarium, respectively, as judged radiographically by closure of the defect at 3 weeks. More soluble forms of BMP-2, used as controls, induced less healing, demonstrating a positive correlation between low solubility, retention in vitro, and healing in vivo. Subsequently, the utility of nglBMP-2 was explored in a prospective veterinary clinical trial for inter-carpal fusion in dogs, replacing the standard-of-care, namely autologous cancellous autograft, with nglBMP-2 in fibrin. In a study of 10 sequential canine patients, fibrin with 600 μg/ml nglBMP-2 performed better than autograft in the first weeks of bone healing and comparably thereafter. Furthermore, a greater fraction of animals treated with nglBMP-2 in fibrin demonstrated bone bridging across each of the treated joints at both 12 and 17 weeks than in animals treated with autograft. These results suggest that evaluation in a human clinical setting of nonglycosylated BMP-2 in fibrin matrices might be fruitful. [Copyright &y& Elsevier]

Copyright of Clinical Oral Implants Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Myosin-binding-protein C (MyBP-C) is a myosin-associate protein of unknown function found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. Using a cDNA clone encoding the fast-type isoform of chicken MyBP-C, we screened a human fetal muscle cDNA library and isolated clones encoding the full-length human fast-type isoform of MyBP-C. cDNA clones encoding the slow-type isoform of human MyBP-C, were also isolated and fully sequenced. Northern-blot analysis demonstrated skeletal muscle-specific expression of these gene products. Using human/hamster somatic-cell hybrids, we were able to map the slow-type MyBP-C to human chromosome 12, and the fast-type MyBP-C to chromosome 19. The cDNA for human fast-type MyBP-C encodes a polypeptide of 1142 amino acids with an expected molecular mass of 128.1 kDa. Comparison of this cDNA with other members of the MyBP family reveals extensive primary-sequence conservation. Each MyBP-C contains seven immunoglobulin C2 motifs and three fibronectin type-III repeats in the arrangement C2-C2-C2-C2-C2-III-III-C2-III-C2. Regions of high identity shared by the chicken and the two human proteins are not restricted to the immunoglobulin and fibronectin motifs. Sequence comparison of all three proteins has allowed us to map a highly conserved region between the first and second C2 motifs, the only large spacer sequence present between motifs in these proteins. [ABSTRACT FROM AUTHOR]

Increased contractile activity as induced by chronic low-frequency stimulation evoked in rat fast-twitch muscle an almost immediate increase in the ratio between structure-bound and free hexokinase. In addition, an up to 14fold rise in total hexokinase activity occurred after two weeks of stimulation indicating that glucose phosphorylation became a limiting step of glucose utilization under these conditions. The increase in hexokinase activity was transitory as prolonged stimulation led to a leveling off and steep decline with an apparent half-life of 2.5 days after three weeks of stimulation. The transient increase in glucose phosphorylating capacity can be explained by previous observations indicating that prolonged stimulation leads to a shift from a carbohydrate-based to a fattyacid-based energy metabolism. Using an isozyme-specific sandwich ELISA, it was shown that both increases and decreases in total hexokinase activity were matched by corresponding changes in the amount of hexokinase isozyme II protein. Increases in both total hexokinase activity (3-4-fold) and hexokinase II protein content were also observed after denervation in rat fast-twitch muscle. In view of reports in the literature, it is suggested that the elevations in hexokinase II observed with increased contractile activity and denervation relate to enhanced glucose uptake and utilization. [ABSTRACT FROM AUTHOR]