The effect of matrix bound parathyroid hormone on bone regeneration

INTRODUCTION: Autogenous bone is the most successful bone-grafting material; however, multiple disadvantages continue to drive developments of improved methods for bone regeneration. AIM: The aim of the present study was to test the hypothesis that an arginine-glycine-aspartic acid (RGD) modified polyethylene glycol-based matrix (PEG) containing covalently bound peptides of the parathyroid hormone (PTH(1-34)) enhances bone regeneration to a degree similar to autogenous bone. MATERIAL AND METHODS: Six American foxhounds received a total of 48 cylindrical titanium implants placed in the mandible between the first premolar and the second molar. Five, respectively, 7 months following tooth extraction, implants were placed into the center of surgically created defects. This resulted in a circumferential bone defect simulating an alveolar defect with a circular gap of 1.5 mm. Four treatment modalities were randomly allocated to the four defects per side: (1) PEG-matrix containing 20 microg/ml of PTH(1-34), and 350 microg/ml cys-RGD peptide, (2) PEG alone, (3) autogenous bone and (4) empty defects. Histomorphometric analysis was performed 4 and 12 weeks after implantation. The area fraction of newly formed bone was determined within the former defect and the degree of bone-to-implant contact (BIC) was evaluated both in the defect region and in the apical region of the implant. For statistical analysis ANOVA and subsequent pairwise Student's t-test were applied. RESULTS: Healing was uneventful and all implants were histologically integrated. Histomorphometric analysis after 4 weeks showed an average area fraction of newly formed bone of 41.7+/-1.8% for matrix-PTH, 26.6+/-4.1% for PEG alone, 43.9+/-4.5% for autogenous bone, and 28.9+/-1.5% for empty defects. After 12 weeks, the respective values were 49.4+/-7.0% for matrix-PTH, 39.3+/-5.7% for PEG alone, 50.5+/-3.4% for autogenous bone and 38.7+/-1.9% for empty defects. Statistical analysis after 4 and 12 weeks revealed significantly more newly formed bone in the PTH(1-34) group compared with PEG alone or empty defects, whereas no difference could be detected against autogenous bone. Regarding BIC no significant difference was observed between the four treatment groups neither at 4 nor at 12 weeks. CONCLUSION: It is concluded that an RGD-modified PEG hydrogel containing PTH(1-34) is an effective matrix system to obtain bone regeneration.

Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection

BACKGROUND: CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. METHODOLOGY/PRINCIPAL FINDINGS: Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C. CONCLUSIONS/SIGNIFICANCE: During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists.

Bone apposition around two different sandblasted and acid-etched titanium implant surfaces: a histomorphometric study in canine mandibles

PURPOSE: The aim of this study was to evaluate bone apposition to a modified sandblasted and acid-etched (SLA) implant surface (modSLA) in the canine mandible as compared with the standard SLA surface. MATERIAL AND METHODS: In this experimental study, all mandibular premolars and first molars were extracted bilaterally in five foxhounds. After a healing period of 6 months, each side of the mandible received six randomly assigned dental implants alternating between the standard SLA and modSLA surface. The dogs were sacrificed at 2 weeks (n=2) or 4 weeks (n=3) after implant placement. Histologic and histomorphometric analyses were then performed for each implant. RESULTS: The microscopic healing patterns at weeks 2 and 4 for the two implant types with the standard SLA and modSLA surfaces showed similar qualitative findings. New bone tissue had already established direct contact with implant surfaces after 2 weeks of healing. The mean percentage of newly formed bone in contact with the implant (BIC) was significantly greater for modSLA (28.2+/-7.9%) than for SLA (22.2+/-7.3%) (P<0.05). This difference was no longer evident after 4 weeks. An increase in BIC for both implant surface types occurred from weeks 2 to 4. This increase was statistically significant when compared with SLA at 2 weeks (P<0.05), but not when compared with modSLA at 2 weeks. CONCLUSION: The data from the present study demonstrate significantly more bone apposition for the modSLA surface than the standard SLA surface after 2 weeks of healing. This increased bone apposition may allow a further reduction of the healing period following implant placement for patients undergoing early loading procedures.