Translating Dental, Oral, and Craniofacial Regenerative Medicine Innovations to the Clinic through Interdisciplinary Commercial Translation Architecture.

Few university-based regenerative medicine innovations in the dental, oral, and craniofacial (DOC) space have been commercialized and affected clinical practice in the United States. An analysis of the commercial translation literature and National Institute for Dental and Craniofacial Research's (NIDCR's) portfolio identified barriers to commercial translation of university-based DOC innovations. To overcome these barriers, the NIDCR established the Dental Oral Craniofacial Tissue Regeneration Consortium. We provide generalized strategies to inform readers how to bridge the "valley of death" and more effectively translate DOC technologies from the research laboratory or early stage company environment to clinical trials and bring needed innovations to the clinic. Three valleys of death are covered: 1) from basic science to translational development, 2) from translational technology validation to new company formation (or licensing to an existing company), and 3) from new company formation to scaling toward commercialization. An adapted phase-gate model is presented to inform DOC regenerative medicine teams how to involve regulatory, manufacturability, intellectual property, competitive assessments, business models, and commercially oriented funding mechanisms earlier in the translational development process. An Industrial Partners Program describes how to conduct market assessments, industry maps, business development processes, and industry relationship management methods to sustain commercial translation through the later-stage valley of death. Paramount to successfully implementing these methods is the coordination and collaboration of interdisciplinary teams around specific commercial translation goals and objectives. We also provide several case studies for translational projects with an emphasis on how they addressed DOC biomaterials for tissue regeneration within a rigorous commercial translation development environment. These generalized strategies and methods support innovations within a university-based and early stage company-based translational development process, traversing the many funding gaps in dental, oral, and craniofacial regenerative medicine innovations. Although the focus is on shepherding technologies through the US Food and Drug Administration, the approaches are applicable worldwide.

[Zoster disease after Shingrix vaccination]. / Zostererkrankung nach Shingrix-Impfung.

Shingrix is a recombinant adjuvant subunit vaccine. The vaccine is approved in Germany for prevention of zoster manifestation and postherpetic neuralgia in adults aged ≥60 years. In the case of bullous skin lesions after vaccination with Shingrix a zoster disease should be considered. Unexpected side effects associated with the vaccination should be reported to the Drug Commission of the German Medical Association.

[Pityriasis rubra pilaris : Successful treatment with ixekizumab]. / Pityriasis rubra pilaris : Eine erfolgreiche Therapie mit Ixekizumab.

Pityriasis rubra pilaris is a rare papulosquamous chronic skin disease. The disease often exists for years and is difficult to treat. Not only is it clinically similar to psoriasis vulgaris, but both diseases also have a similar cytokine profile. The successful use of biologicals is frequently reported in case reports. Studies with large numbers of cases are lacking.

Selective bundle tensioning in double-bundle MPFL reconstruction to improve restoration of dynamic patellofemoral contact pressure.

PURPOSE: To evaluate the optimal graft tension angles in a medial patellofemoral ligament (MPFL) reconstruction with selective bundle tensioning in order to restore patellofemoral contact pressure distributions closest to the native state. METHODS: Twelve human cadaveric knee specimens were mounted with the femur on a custom-made fixation device allowing free range of motion in the knee joint for testing. Using a sensitive pressure film (Tekscan) patellofemoral contact pressure was measured in 15° intervals during a dynamic flexion movement from 0°-90° in the native state, in cut MPFL and after MPFL-reconstruction with a gracilis tendon. The graft was separated in two bundles and was fixed independently on the patella using two knotless anchors. Two groups were made with either the proximal or distal bundle fixed at the femur at a knee flexion angle of 30° and the corresponding other bundle subsequently fixed at the femur at 15°, 45°, 60°, 75° and 90° of knee flexion using extra-cortical fixation and controlled tension of 2N in both groups. The sequence of the flexion angles at the graft fixation was alternated. Pressure measurements were repeated after every fixation of the graft. RESULTS: Cutting the MPFL resulted in significantly reduced patellofemoral contact pressure at all flexion angles. After MPFL reconstruction the patellofemoral contact pressure remained significantly reduced during dynamic knee flexion in all tested double-bundle combinations (p < 0.05) except for fixation of the proximal bundle in 30° and the distal bundle in 75°. Selective evaluation of lateral patellofemoral contact pressure, however, showed significant reduction in all tested double-bundle combinations (p < 0.05) from 15° to 90°. Evaluation of isolated medial patellofemoral pressure changes showed no significant difference in all tested combinations compared to the intact knee. Furthermore, evaluation of the isolated proximal and distal patellofemoral contact pressure also revealed a significantly reduced contact pressure in all tested double-bundle combinations (p < 0.05) except for fixation of the proximal bundle in 30° and the distal bundle in 75°. CONCLUSION: According to this study, selective bundle tensioning in anatomic MPFL-reconstruction should be considered as an easy and more anatomic alternative to current popular techniques to restore patella kinematics and give clear recommendation about knee flexion angle and tension during fixation. Although tensioning two bundles separately may further improve clinical results. If performed, fixation of the graft is recommended under low tension (2N) with the proximal bundle at 30° and the distal bundle at 75° of knee flexion.

[Endoprosthetic replacement following intercalary resection]. / Endoprothetische Rekonstruktion nach interkalarer Resektion.

BACKGROUND: Endoprosthetic replacement is a valuable treatment option following intercalary resection of bone tumours in the diaphysis. OBJECTIVES: To identify indication, operative technique, implants currently available, literature results and alternative procedures for the alloplastic reconstruction of segmental bone defects. MATERIALS AND METHODS: This review article summarizes the authors' own experiences and relevant clinical studies focussing on this topic. RESULTS: According to the literature, 10-year-survival rates of intercalary endoprostheses range between 64 and 80%. Yet, comparisons between different publications are difficult due to the limited number of cases, different implants, follow-up periods and the heterogeneous patient populations. Biological alternatives for reconstruction are autologous bone transplantation, distraction osteogenesis and bone transport, allogenic bone transplantation, and the induced membrane technique. Innovative tissue engineering approaches are still limited to preclinical testing. CONCLUSIONS: Short- to mid-term results for segmental endoprostheses following intercalary resections are satisfactory and may be regarded as superior to those of biological reconstructions due to the immediate full weight-bearing capability. However, they are mainly applied for elderly patients and in palliative situations because of potential long-term complications.

Biological and Mechanical Evaluation of Novel Prototype Dental Composites.

The breakdown of the polymeric component of contemporary composite dental restorative materials compromises their longevity, while leachable compounds from these materials have cellular consequences. Thus, a new generation of composite materials needed to be designed to have a longer service life and ensure that any leachable compounds are not harmful to appropriate cell lines. To accomplish this, we have developed concurrent thiol-ene-based polymerization and allyl sulfide-based addition-fragmentation chain transfer chemistries to afford cross-linked polymeric resins that demonstrate low shrinkage and low shrinkage stress. In the past, the filler used in dental composites mainly consisted of glass, which is biologically inert. In several of our prototype composites, we introduced fluorapatite (FA) crystals, which resemble enamel crystals and are bioactive. These novel prototype composites were benchmarked against similarly filled methacrylate-based bisphenol A diglycidyl ether dimethacrylate / triethylene glycol dimethacrylate (bisGMA/TEGDMA) composite for their cytotoxicity, mechanical properties, biofilm formation, and fluoride release. The leachables at pH 7 from all the composites were nontoxic to dental pulp stem cells. There was a trend toward an increase in total toughness of the glass-only-filled prototype composites as compared with the similarly filled bisGMA/TEGDMA composite. Other mechanical properties of the glass-only-filled prototype composites were comparable to the similarly filled bisGMA/TEGDMA composite. Incorporation of the FA reduced the mechanical properties of the prototype and bisGMA/TEGDMA composite. Biofilm mass and colony-forming units per milliliter were reduced on the glass-only-filled prototype composites as compared with the glass-only-filled bisGMA/TEGDMA composite and were significantly reduced by the addition of FA to all composites. Fluoride release at pH 7 was greatest after 24 h for the bisGMA/TEGDMA glass + FA composite as compared with the similarly filled prototypes, but overall the F- release was marginal and not at a concentration to affect bacterial metabolism.

Bernese periacetabular osteotomy through a double approach : Simplification of a surgical technique.

OBJECTIVE: Reorientation of the acetabulum to normalize load transfer or avert femoroacetabular pincer impingement to prevent osteoarthritis of the hip. INDICATIONS: Persisting acetabular dysplasia after closure of growth plates or acetabular malrotation. CONTRAINDICATIONS: High dislocation of hip, secondary acetabulum, increased misalignment on functional X­ray, high-grade mobility restriction. Relative: degenerative changes, advanced age. SURGICAL TECHNIQUE: Bernese periacetabular osteotomy through two incisions; all bone cuts are carried out under direct vision. The osteotomies are equivalent to the classic Ganz method. In a slightly tilted forward lateral decubitus position, a posterior incision is applied for the ischium osteotomy and the caudal portion of the retroacetabular osteotomy. The pubis and ilium osteotomies are performed in a supine position through an anterior approach with subsequent reorientation and screw fixation. The rectus femoris is not dissected unless joint exposure is required. POSTOPERATIVE MANAGEMENT: Partial weight bearing with 20 kg for the first 6 weeks postoperatively, followed by stepwise transition to full loads after radiological control. RESULTS: In total, 34 patients (37 hips) were followed up for 20.4 ± 10.3 months. Tönnis osteoarthritis scale levels remained constant. The center-edge angle of Wiberg increased from 13.2 ± 7.5° to 26.5 ± 6.7°, the Tönnis angle (acetabular index) changed from 13.8 ± 6.5° to 3.4 ± 4.4°. At follow-up, the Merle d'Aubigné and Postel score was 16.5 ± 1.4; the modified Harris hip score 87.6 ± 13.9 and the International hip outcome tool (iHOT)-12 78.2 ± 20.3 points. The mean surgical time was 213 ± 29 min. Severe complications were not observed.

[Diagnostics and treatment of osteoid osteoma]. / Diagnostik und Therapie des Osteoidosteoms.

BACKGROUND: Osteoid osteoma is the third most common benign bone tumor and typically induces pain that is worse at night. OBJECTIVE: To identify the epidemiological, pathogenetic, histological and radiological characteristics of osteoid osteoma and to present the broad variety of treatment options. MATERIAL AND METHODS: This review article summarizes relevant clinical studies and meta-analyses on this topic. RESULTS: Osteoid osteoma is characterized by a central nidus smaller than 1.5 cm in diameter with surrounding bone sclerosis. In the majority of cases, the tumor occurs in the long bones of the lower extremities and is predominantly manifested in patients aged between 5 and 25 years. Pain is mediated by prostaglandins, which stimulate afferent peripheral nerve fibers. Besides plain radiographs, thin-section computed tomography represents the gold standard of diagnostics but should be complemented by magnetic resonance or nuclear medicine imaging modalities. The conservative treatment consists of long-term therapy with non-steroidal anti-inflammatory drugs. Minimally invasive radiofrequency ablation of the nidus is the current operative treatment of choice. CONCLUSION: Success rates of radiofrequency ablation and other minimally invasive procedures are high while treatment costs and length of hospital stay are low. Thus, open surgical curettage is reserved for rare indications and en bloc excision of the nidus should only be performed in cases of recurrent lesions.

Poor sleep quality is associated with impaired glucose tolerance in women after gestational diabetes.

We analyzed the association of sleep quality and glucose metabolism in women after gestational diabetes (pGDM) and in women after normoglycemic pregnancy (controls). Data during pregnancy and a visit within the first 15 months after delivery were collected from 61 pGDM and 30 controls in a prospective cohort study. This included a medical history, physical examination, questionnaires (Pittsburgh Sleep Quality Index (PSQI), and Perceived Stress Scale (PSS)), and 5-point oral glucose tolerance test with insulin measurements to determine indices of insulin sensitivity and insulin secretion. We used Spearman correlation coefficients and multivariate regression models for analysis.9.3 ± 3.2 months after delivery, pGDM had significantly higher fasting and 2 h glucose levels and lower insulin sensitivity than controls. There was no significant difference in age, BMI and sleep quality as assessed with the PSQI between the two groups. The PSQI score correlated with the ogtt-2 h plasma glucose in pGDM (δ = 0.41; p = 0.0012), but not in controls. This association was confirmed with a multivariate linear regression model with adjustment for age, BMI and months post-delivery. Perceived stress was an independent risk factor (OR 1.12; 95% CI 1.02-1.23) for impaired sleep. Our findings suggest that post-delivery sleep quality significantly influences glucose tolerance in women after GDM and that impaired sleep is associated with increased stress perception. Measures to improve of sleep quality and reduce perceived stress should therefore be tested as additional strategies to prevent progression to type 2 diabetes after GDM.

[Medial unicondylar knee replacement]. / Die mediale monokondyläre Kniegelenkprothese.

BACKGROUND: Unicondylar knee replacement (UKA) is a viable alternative to high tibial osteotomy (HTO) and total knee replacement in the treatment of medial osteoarthritis of the knee. With the correct indication, the results of UKA and HTO are comparable. RESULTS: In comparison with the results of total knee replacements, UKA leads to faster rehabilitation, superior postoperative range of motion, and higher postoperative activity levels. Despite the excellent long-term results, the survival rate is inferior to the results of total knee replacement. The major causes for failure are progression of osteoarthritis in the lateral and patellofemoral joint as well as the loosening of the tibial component. CONCLUSION: The conversion to total knee replacement can mostly be performed without problems. However, the expected results are inferior to primary total knee replacement and the reported revision rates are higher.