Effects of Strontium-Doped ß-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model.

It was hypothesized that strontium (Sr)-doped ß-tricalcium phosphate (TCP)-based scaffolds have a positive effect on the regeneration of large bone defects (LBD). Readouts in our mice models were nuclear factor-kappa beta (NF-κB) activity and vascular endothelial growth factor receptor-2 (VEGFR-2) promoter activity during the healing process. A 2-mm critical-size femoral fracture was performed in transgenic NF-κB- and VEGFR-2-luciferase reporter mice. The fracture was filled with a 3D-printed ß-TCP scaffold with or without Sr. A bioluminescence in-vivo imaging system was used to sequentially investigate NF-κB and VEGFR-2 expression for two months. After sacrifice, soft and osseous tissue formation in the fracture sites was histologically examined. NF-κB activity increased in the ß-TCP + Sr group in the latter stage (day 40-60). VEGFR-2 activity increased in the + Sr group from days 0-15 but decreased and showed significantly less activity than the ß-TCP and non-scaffold groups from days 40-60. The new bone formation and soft tissue formation in the + Sr group were significantly higher than in the ß-TCP group, whereas the percentage of osseous tissue formation in the ß-TCP group was significantly higher than in the ß-TCP + Sr group. We analyzed longitudinal VEGFR-2 promoter activity and NF-κB activity profiles, as respective agents of angiogenesis and inflammation, during LBD healing. The extended inflammation phase and eventually more rapid resorption of scaffold caused by the addition of strontium accelerates temporary bridging of the fracture gaps. This finding has the potential to inform an improved treatment strategy for patients who suffer from osteoporosis.

The protective effect of platelet released growth factors and bone augmentation (Bio-Oss®) on ethanol impaired osteoblasts.

BACKGROUND: Chronic alcohol consumption is a known limiting factor for bone healing. One promising strategy to improve bone augmentation techniques with Bio-Oss® in oral and maxillofacial surgery might be the supportive application of platelet-concentrated biomaterials as platelet-released growth factor (PRGF). To address this matter, we performed an in vitro study investigating the protective effects of PRGF and Bio-Oss® in ethanol (EtOH) treated osteoblasts. METHODS: The SAOS-2 osteosarcoma cell line, with and without EtOH pretreatment was used. The cell viability, proliferation and alkali phosphatase activity (ALP) after application of 0%, 5% and 10% PRGF and Bio-Oss® were assessed. RESULTS: The application of PRGF and Bio-Oss® in EtOH impaired osteoblasts showed a significant beneficial influence increasing the viability of the osteoblasts in cell culture. The synergistic effect of Bio-Oss® and 5% PRGF on the proliferation of osteoblasts was also demonstrated. Bio-Oss® only in combination with PRGF increases the alkaline phosphatase (ALP) activity in EtOH pretreated cells. CONCLUSIONS: These results indicate that the simultaneous application of PRGF and Bio-Oss® inhibits EtOH induced bone healing impairment. Furthermore, in the cells, PRGF induced a protective mechanism which might promote bone regeneration.

Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease.

The etiology and pathogenesis of rheumatoid arthritis (RA) are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP). The main objective of this work is to examine the influences of platelet-released growth factor (PRGF) on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1ß. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes.

A Novel Experimental Method for Penile Augmentation Urethroplasty With a Combination of Buccal Mucosa and Amniotic Membrane in a Rabbit Model.

OBJECTIVE: To investigate the results of penile urethral reconstruction using amniotic membrane (AM) and buccal mucosa (BM) grafts, and the simultaneous use of both in a rabbit model. MATERIALS AND METHODS: A total of 28 male rabbits were divided into 4 groups according to grafting style: group 1 (AM), group 2 (BM), group 3 (BM + AM), and group 4 (sham). A standardized urethral defect was created in the 3 initial groups. The sham group underwent only a ventral vertical urethral incision and primary re-suturation. AM grafts were used in group 1, and BM grafts were used in groups 2 and 3. AM grafts were affixed to the BM grafts in group 3 as a covering tissue. Urethrography and endoscopy were performed after the 1st and 2nd months of grafting. The penises were subjected to histopathologic and immunohistochemical assessment for fibroblast growth factor and vascular endothelial growth factor expression. RESULTS: Dehiscence and fistula developed in group 1, whereas 2 fistulas were observed in group 2. No complications developed in group 3. Epithelization at urethras was observed at 4 weeks in all groups, but transformation to urothelial epithelialization occurred at 8 weeks. Marked amelioration and epithelial transformation were observed in group 3. The most prominent fibroblast growth factor expression was observed in group 3. Vascular endothelial growth factor expression was completely negative in group 3 at 8 weeks, indicating complete healing. CONCLUSION: The simultaneous use of AM and BM for ventral onlay penile urethroplasty provides better tissue healing and lower complication rates in comparison to BM alone. Further animal studies or clinical applications are needed.

Multidimensional approach to teaching anatomy-Do gender and learning style matter?

BACKGROUND: The aim of this study was to assess the impact of two teaching interventions (ultrasound and arthroscopy) in a peer teaching (PT) environment on anatomy examination scores and also to examine the influence of gender and learning style on these scores. METHODS: We randomly assigned 484 second year medical students to one of three groups: musculoskeletal ultrasound (MSUS), arthroscopy (ASC) and control (CON). The MSUS- and the ASC-group attended two additional training sessions in ultrasound or arthroscopy; the CON-group received no additional lessons. Students were asked to complete Kolb's Learning Style Inventory test. We assessed differences in anatomical knowledge (multiple choice (MC) exam) and subjective evaluation with respect to gender and learning style. RESULTS: There were no relevant differences between the three groups regarding the MC exam. Acceptance of the peer teaching concept was good. All students preferred ultrasound to arthroscopy and thought that they learned more from ultrasound despite the fact that they rated the instructors as less competent and needed more time to gain in-depth knowledge. There was no significant effect of gender on evaluation results. Arthroscopy was best enjoyed by accommodators according to Kolb's Inventory and least by divergers, who found that they had learned a lot through ultrasound. The improvement in spatial conceptualization was greatest for accommodators and worst for assimilators. CONCLUSION: Gender and learning style had no impact on quantitative parameters. Qualitative analysis, however, revealed differences for learning style and further evaluation is warranted to assess the impact on medical education.

A Novel Approach to Penile Augmentation Urethroplasty Using Buccal Mucosa and Amniotic Membrane: A Pilot Study in a Rabbit Model.

OBJECTIVE: To evaluate and compare the success of amniotic membrane (AM) and buccal mucosa (BM) grafts and simultaneous use of both in penile augmentation urethroplasty in rabbits. MATERIALS AND METHODS: A total of 12 New Zealand rabbits were divided into 3 groups by grafting style: Group 1 (AM), Group 2 (BM), and Group 3 (simultaneous use of BM and AM). In all animals, a standardized urethral defect was created. BM and AM were obtained from the rabbits. Solely AM grafts were affixed to the defects in Group 1, solely BM grafts were affixed to the urethral defects in Group 2, and simultaneous AM + BM grafts were affixed in Group 3. At 4 and 8 weeks, the penises were subject to histological assessment of subepithelial fibrosis, epithelial transformation, and inflammatory reaction. RESULTS: Stenosis was detected in none of the groups. A dehiscence was developed in one rabbit in Group 1 and a fistula was developed in one rabbit in Group 2. After 4 weeks, minimal subepithelial fibrosis and inflammatory reaction were observed in Group 2, while subepithelial fibrosis was not in Groups 3. After 8 weeks, subepithelial connective tissue proliferation was moderate in Group 2, at both 4th and 8th weeks in Group 2. After 8 weeks, the best epithelial transformations were observed in Group 3. CONCLUSION: In an animal model, the simultaneous use of AM and BM grafts following acute urethral injury may be feasible for penile augmentation urethroplasty. Further study is needed.

Locked minimally invasive plating versus fourth generation nailing in the treatment of AO/OTA 31A2.2 fractures: A biomechanical comparison of PCCP(®) and Intertan nail(®).

INTRODUCTION: Locked minimally invasive plating and fourth generation nailing potentially could reduce the complication rate in the treatment of trochanteric femur fractures by its rotational stability and providing better lateral cortical support. The purpose of this study was (1) to compare the biomechanical properties of the Percutaneous compression plate (PCCP) and the Intertan nail (IT) with regards to implant failure and (2) to assess dynamic stability coefficients in an unstable AO/OTA 31A2.2 fracture model. METHODS: In paired femurs, a standardised unstable trochanteric femur fracture was induced by an oscillating saw. The fractures were stabilised by either the PCCP (Orthofix, McKinney, TX, USA) or the IT (Smith & Nephew, Memphis, TN, USA). All femurs were loaded with 300N, followed by an increase in load until failure using 300N each time (2000 cycles each, 0.5Hz). After every load step the samples were assessed visually and radiographically. We measured migration and performed a survival analysis. RESULTS: 16 fractures were induced in 8 paired human specimens (mean age: 84 years, 61-100 years). The mean stiffness (PCCP vs. IT: 249±124N/mm vs. 273±153N/mm; p=0.737) was comparable. The IT proved superior to the PCCP with regard to the number of cycles reached before failure occurred (PCCP vs. IT: 12,691±4733 vs. 15,313±4875 cycles; p=0.023). Except for a higher axial migration of the IT at failure point (PCCP vs. IT: 1.3mm vs. 4.3mm; p=0.028) there were no differences between the intra- and extramedullary implants, not even in terms of rotational stability along the femoral neck axis. A fracture of the femoral neck caused test abortion in both implants in most cases. CONCLUSION: This study showed a superiority of the IT compared with the PCCP with regards to number of cycles achieved under sequential load increases for unstable trochanteric femur fractures. The stiffness was comparable. Both implants showed a high rotational stability and a support of the lateral wall. STUDY TYPE: Biomechanical study.

Supraclavicular osteocutaneous free flap: clinical application and surgical details for the reconstruction of composite defects of the nose.

The supraclavicular fasciocutaneous flap is a well-recognized flap in head and neck reconstruction. In this report, we describe for the first time a variation of this flap, the osteocutaneous supraclavicular (SOC) free flap, which was used to reconstruct a composite nasal defect. The defect arose after resection of a recurrent squamous cell carcinoma and involved dorsal nasal skin, cartilage, and the entire nasal bone. A 6 cm × 4 cm size flap including skin, subcutaneous tissue, and a vascularized cortico-periosteal segment of the clavicle was raised based on the transverse cervical artery. The flap survived with no complications. A satisfactory aesthetic outcome was achieved following two revision procedures. We believe that the incorporation of bone to the supraclavicular flap may expand its applications in reconstruction of composite nasal and facial defects.

Reconstruction after orbital exenteration using gracilis muscle free flap.

BACKGROUND: Orbital exenteration (OE) is a disfiguring procedure, which typically includes the removal of the entire eyeball including the globe, extraocular muscles, and periorbital soft tissues after malignancies excision or trauma. Several methods of orbital reconstruction have been attempted with varying success. In this report, we analyze results of the use of gracilis muscle free flap for reconstruction of OE defects and its feasibility for prosthetic rehabilitation. METHODS: Nine consecutive patients treated at the China Medical University Hospital of Taichung during January 2009 to January 2013, who had gracilis free flap reconstruction after OEs, were retrospectively reviewed. Cancer in six patients and trauma in remaining three patients was the cause for OE. RESULTS: Nine patients who underwent reconstruction with gracilis free tissue transfer had a successful outcome. There was not any donor or recipient site morbidity; however, one patient was deceased during follow-up period due to metastasis. The mean follow-up period was 23.5 months. Cosmetic results were acceptable both to patients and to surgeons. CONCLUSIONS: Gracilis free flap to repair OE defects may be a safe alternative for reconstruction. It provides a larger volume of well-vascularized tissue, greater placement flexibility, and minor donor site morbidity without any significant functional deficit.

Is percutaneous suturing superior to open fibrin gluing in acute Achilles tendon rupture?

PURPOSE: Open fibrin gluing is reported to enable anatomical reconstruction with less soft tissue compromise than suture repair. Our main objective was to compare the complication rate, function, pain and disability of the two operative approaches of percutaneous suture using the Paessler technique and open fibrin gluing. METHODS: Sixty-four patients (two centres, retrospective cohort study, 2000-2009) who had undergone acute Achilles tendon repair with either percutaneous suture (n = 27; 44 years) or open fibrin glue (n = 37; 45 years) took part in a follow-up examination after a median of 63 months (range, six to 180). Ankle range of motion, calf and ankle circumferences and return to work and sports activities were evaluated. Isokinetic und sonographic evaluation results were retrieved. RESULTS: Complications were noted in 22 patients (34 %). Delayed wound healing without evidence of surgical site infection was found in three patients in the fibrin group and two patients in the suture group. Postoperative scar tenderness described as pain at the rim of the shoe was significantly more frequent in the suture group (p = 0.03). Re-rupture requiring re-operation occurred in one patient. Transient paresthesia of the heel occurred in 12 patients. No sural nerve lesions were reported. There was no significant difference between groups regarding lower leg circumference, disability, or function. Ultrasound and isokinetic measurements did not reveal a significant difference between the two methods. CONCLUSIONS: The present study suggests that open fibrin gluing is a reasonable alternative to percutaneous repair of acute ruptures of the Achilles tendon and both techniques can yield reliably good results.

Nrf2 deficiency impairs fracture healing in mice.

Oxidative stress plays an important role in wound healing but data relating oxidative stress to fracture healing are scarce. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the major transcription factor that controls the cellular defence essential to combat oxidative stress by regulating the expression of antioxidative enzymes. This study examined the impact of Nrf2 on fracture healing using a standard closed femoral shaft fracture model in wild-type (WT) and Nrf2-knockout (Nrf2-KO)-mice. Healing was evaluated by histology, real-time RT-PCR, µCT and biomechanical measurements. We showed that Nrf2 expression is activated during fracture healing. Bone healing and remodelling were retarded in the Nrf2-KO compared to the WT-mice. Nrf2-KO-mice developed significantly less callus tissue compared to WT-mice. In addition, biomechanical testing demonstrated lower strength against shear stress in the Nrf2-KO-group compared to WT. The expression of vascular endothelial growth factor (VEGF) and osteocalcin is reduced during fracture healing in Nrf2-KO-mice. Taken together, our results demonstrate that Nrf2 deficiency in mice results in impaired fracture healing suggesting that Nrf2 plays an essential role in bone regeneration. Pharmacological activation of Nrf2 may have therapeutic potential for the enhancement of fracture healing.

Morphological and morphometric evaluation of the ilium, fibula, and scapula bones for oral and maxillofacial reconstruction.

This study aimed to evaluate the osteometric boundaries of the ilium, fibula, and scapula beyond which reconstruction of oromandibular and craniofacial defects, using these free flaps, may not be optimal. Fibula, scapula, and iliac bones were obtained bilaterally from 33 female and 27 male European adult cadavers (n = 60). Adapting classical anthropometric methods to surgical needs by modifying the measuring bone localizations and measurement points, a measuring system of osteometry and morphometry was used, to quantify the usable bone length of the iliac crest, fibula, and lateral border of the scapula and to localize an oval region (OR) in the ilium. The thin, translucent OR of ilium was localized 62.4 ± 5.6 mm posterior to the maximum concavity between the anterior superior (ASIS) and anterior inferior iliac spine and 26.7 ± 6 mm caudal to the intermediate line of the iliac crest. The available iliac crest was measured from ASIS to the posterior superior iliac spine (PSIS) 247.5 ± 12.6 mm, fibula supplied 170.2 ± 19.1 mm harvestable bone, and the lateral border of the scapula 94.3 ± 8.5 mm [Corrected]. The OR influenced the harvestable bone shape and volume of the ilium. Measuring of the localization points of OR, we found that the size of the OR was very variable and that the height of the neomandible reconstructed with iliac crest might alter with aging. Our findings contribute with knowledge of detailed morphometric measurements on commonly used donor bones to the planning strategies of volumetric defects in oral and maxillofacial region by precise osteometric localization method of OR and relativized length measurements.

The accuracy of computer-assisted primary mandibular reconstruction with vascularized bone flaps: iliac crest bone flap versus osteomyocutaneous fibula flap.

BACKGROUND: The intention of mandibular reconstruction is to restore the complex anatomy with maximum possible functionality and high accuracy. The aim of this study was to evaluate the accuracy of computer-assisted surgery in primary mandibular reconstruction with an iliac crest bone flap compared with an osteomyocutaneous fibula flap. MATERIALS AND METHODS: Preoperative computed tomography data of the mandible and the iliac crest or fibula donor site were imported into a specific surgical planning software program. Surgical guides were manufactured using a rapid prototyping technique for translating the virtual plan, including information on the transplant dimensions and shape, into real-time surgery. Using postoperative computed tomography scans and an automatic surface-comparison algorithm, the actual postoperative situation was compared with the preoperative virtual simulation. RESULTS: The actual flap position showed a mean difference from the virtual plan of 2.43 mm (standard deviation [SD] ±1.26) and a surface deviation of 39% <2 mm and 15% <1 mm for the iliac crest bone flap, and a mean difference of 2.18 mm (SD ±1.93) and a surface deviation of 60% <2 mm and 37% <1 mm for the osteomyocutaneous fibula flap. The position of the neomandible reconstructed with an osteomyocutaneous fibula flap indicated a mean difference from the virtual plan of 1.25 mm (SD ±1.31) and a surface deviation of 82% <2 mm and 57% <1 mm, in contrast to a mean difference of 1.68 mm (SD ±1.25) and a surface deviation of 63% <2 mm and 38% <1 mm for the neomandible after reconstruction with an iliac crest bone flap. For shape analysis, a similarly high accuracy could be calculated for both flaps. CONCLUSION: Virtual surgical planning is an effective method for mandibular reconstruction with vascularized bone flaps, and can help to restore the anatomy of the mandible with high accuracy in position and shape. It seems that primary mandibular reconstruction with the osteomyocutaneous fibula flap is more accurate compared with the vascularized iliac crest bone flap.

Role of platelet-released growth factors in detoxification of reactive oxygen species in osteoblasts.

INTRODUCTION: Oxidative stress can impair fracture healing. To protect against oxidative damage, a system of detoxifying and antioxidative enzymes works to reduce the cellular stress. The transcription of these enzymes is regulated by antioxidant response element (ARE). The nuclear factor (erythroid-derived 2)-like2 (Nrf2) plays a major role in transcriptional activation of ARE-driven genes. Recently it has been shown that vascular endothelial growth factor (VEGF) prevents oxidative damage via activation of the Nrf2 pathway in vitro. Platelet-released growth factor (PRGF) is a mixture of autologous proteins and growth factors, prepared from a determined volume of platelet-rich plasma (PRP). It has already used to enhance fracture healing in vitro. The aim of the present study was to elucidate if platelets can lead to upregulation of VEGF and if platelets can regulate the activity of Nrf2-ARE system in primary human osteoblast (hOB) and in osteoblast-like cell line (SAOS-2). METHODS: Platelets and PRGF were obtained from healthy human donors. HOB and SAOS-2 osteosarcoma cell line were used. The ARE activity was analysed using a dual luciferase reporter assay system. We used Western blot to detect the nuclear accumulation of Nrf2 and the amount of cytosolic antioxidant Thioredoxin Reductase-1 (TXNRD-1), Heme Oxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1 (NQO1). Gene expression analysis was performed by real-time RT PCR. ELISA was used for the quantification of growth factors. RESULTS: The activity of ARE was increased in the presence of PRGF up to 50%. Western blotting demonstrated enhanced nuclear accumulation of Nrf2. This was followed by an increase in the protein expression of the aforementioned downstream targets of Nrf2. Real-time RT PCR data showed an upregulation in the gene expression of the VEGF after PRGF treatment. This was confirmed by ELISA, where the treatment with PRGF induced the protein level of VEGF in both cells. CONCLUSIONS: These results provide a new insight into PRGF's mode of action in osteoblasts. PRGF not only leads to increase the endogenous VEGF, but also it may be involved in preventing oxidative damage through the Nrf2-ARE signalling. Nrf2 activation via PRGF may have great potential as an effective therapeutic drug target in fracture healing.

Effect of VEGF gene therapy and hyaluronic acid film sheath on peripheral nerve regeneration.

Functional nerve regeneration after reconstructive nerve surgery remains unsatisfying. In this study, vascular endothelial growth factor (VEGF) gene therapy combined with a hyaluronic acid (HA)-enriched microenvironment in nerve regeneration was investigated. Sciatic nerve was transected, and end-to-end neurorrhaphy was performed on 32 male Sprague-Dawley rats, which were randomly divided into four groups (n = 8 per group): nerve coaptation without treatment (group I); nerve coaptation covered with HA film sheath (group II); nerve coaptation with intramuscular VEGF gene in plasmid injection (group III); and nerve coaptation combined with HA film sheath and intramuscular VEGF gene in plasmid injection (group IV). Contralateral sciatic nerves were used as control. VEGF expression was verified from gluteal muscle biopsies surrounding the sciatic nerve by reverse transcriptase-PCR. Electrophysiological, histopathological, and electron microscopic evaluations were performed after 4 weeks. Mean peak amplitude of groups I-IV and nonoperated sciatic nerve were 4.5 ± 0.6 mV, 6.4 ± 0.4 mV, 6.7 ± 0.5 mV, 8.5 ± 0.4 mV, and 9.8 ± 0.5 mV, respectively. Mean myelinated axonal counts of groups I-IV and nonoperated sciatic nerve were 105 ± 24, 165 ± 19, 181 ± 22, 271 ± 23, and 344 ± 17, respectively. Treatment with HA film sheath coverage combined with intramuscular VEGF gene in plasmid injection yielded statistically significant higher peak amplitudes and myelinated axonal counts (P < 0.001). In addition, significantly less scar formation with HA administration (groups II and IV; P < 0.001) was found. Thus, it was found that VEGF might crucially regulate nerve regeneration processes and that HA can reduce the scar formation. This study showed that the combination of HA film sheath and VEGF gene may synergistically promote peripheral nerve regeneration.

Modified Charles procedure and lymph node flap transfer for advanced lower extremity lymphedema.

INTRODUCTION: Treatment of advanced lymphedema remains a challenge in reconstructive surgery. Microsurgical techniques seem to be effective in early stage lymphedema, however in advanced stages their role is not well established. In this study, we present a novel approach for advanced lymphedema combining excisional procedure (Charles) with transferring lymph node flap. PATIENTS AND METHOD: From 2010 to 2013, 24 patients (18 women, six men, mean age 53 years old) presented with late stage of lower extremity lymphedema. The modification of Charles procedure consisted of preserving the superficial venous system of the dorsum of the foot and the lesser saphenous vein, which were used for the venous anastomosis of the transferred lymph node flap. In 11 patients we transferred the inguinal lymph node flaps from the contralateral site, meanwhile in 13 patients supraclavicular lymph node flaps were used. RESULTS: Maximum reduction of the lymphedema was achieved. No major complication was detected postoperatively. There were two patients with partial loss of the skin graft necessitated re-grafting. All the lymph node flaps survived well. The patients resumed normal daily activities within a period of 2 months. The mean follow-up was 14 months (3-26 months). During this period, no recurrence of the lymphedema was observed. CONCLUSION: The combination of the modified Charles procedure with vascularized transferring of lymph node flap is an effective method for treatment of advanced stage lymphedema.

Morphometric study of the scapular free flap and the free rib osteomyocutaneous flap.

The scapula free flap is often the first choice for reconstruction of bony defects of the facial skeleton. However, the vascularised rib as part of a free rib osteomyocutaneous flap may be a suitable second choice. We have investigated the morphology and clinical dimensions of the 7th rib and the scapula, and the ability of the available bone to carry dental implants. The age and sex of the cadaver, and the donor side, were also recorded. The dimensions of the scapulas and 7th ribs (n=130 of each) from 65 cadavers were measured at 4 different points using osteometric methods. Examination showed that bone from the scapula and 7th rib were sufficient for placement of implants. The 7th rib gave reliable measurements for both height and width, and a consistent relation between compact and cancellous bone. Although the scapula provided adequate compact and cancellous bone, there were variations depending on the segment of bone chosen. Bones from male cadavers were more suitable for implantation. In both the scapula and the 7th rib ageing had a significant adverse effect in only one dimension. Most points of measurement have satisfactory bony dimensions for insertion of dental implants.

Nrf2 protects against TWEAK-mediated skeletal muscle wasting.

Skeletal muscle (SM) regeneration after injury is impaired by excessive inflammation. Particularly, the inflammatory cytokine tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a potent inducer of skeletal muscle wasting and fibrosis. In this study we investigated the role of Nrf2, a major regulator of oxidative stress defence, in SM ischemia/reperfusion (I/R) injury and TWEAK induced atrophy. We explored the time-dependent expression of TWEAK after I/R in SM of Nrf2-wildtype (WT) and knockout (KO) mice. Nrf2-KO mice expressed significant higher levels of TWEAK as compared to WT mice. Consequently, Nrf2-KO mice present an insufficient regeneration as compared to Nrf2-WT mice. Moreover, TWEAK stimulation activates Nrf2 in the mouse myoblast cell line C2C12. This Nrf2 activation inhibits TWEAK induced atrophy in C2C12 differentiated myotubes. In summary, we show that Nrf2 protects SM from TWEAK-induced cell death in vitro and that Nrf2-deficient mice therefore have poorer muscle regeneration.

Effect of SDF-1 α on endogenous mobilized and transplanted stem cells in regeneration after myocardial infarction.

Aim of the presented study was to investigate the role of stromal derived factor 1 (SDF-1α) in mobilizing stem cells in combination with endothelial progenitor cell (EPC) transplantation in a regenerative strategy for myocardial infarction therapy in a murine ischemia/reperfusion model. Initially bone marrow was eradicated and reconstituted with the use of green fluorescent protein (GFP) labelled allogenic cells. After reconstitution, myocardial ischemia was induced by temporary ligation of the left anterior descending coronary artery (LAD) in C57/B16 mice and maintained for 1h. After reperfusion, EPCs (1 x 10(6) cells) or medium were injected directly into the border zones of the infarcted areas. In addition, the animals were divided in groups treated or not with specific antibodies against SDF-1α. 4 weeks after transplantation, echocardiography revealed a significantly decreased left ventricular function after application of EPCs in anti-SDF-1α treated animals compared to untreated groups. Histology revealed that EPC transplantation and anti-SDF-1α treatment diminished the amount of intramyocardially attracted GFP positive bone marrow cells. Interestingly, no significant changes in the density of CD31+ vessel structures compared to EPC transplantation alone were detectable in anti-SDF-1α treated groups. Anti-SDF-1α treatment also increased numbers of inflammatory cells (monocytes and neutrophiles) in infarcted areas. Rate of apoptotic cells and proliferation after transplantation did not differ. In conclusion, transplanted endothelial progenitor cells as well as SDF-1α are key factors in mobilization of endogenous bone marrow cells towards infarcted myocardium. Anti-SDF-1α treatment leads to a significant decreased left ventricular function, alters the inflammatory processes, but does not lead to significant alterations in neovascularization or collagen content of infarcted areas.