Rüdiger Zimmerer

A prospective multicenter study to compare the precision of posttraumatic internal orbital reconstruction with standard preformed and individualized orbital implants

PURPOSE A variety of implants are available for orbital reconstruction. Titanium orbital mesh plates are available either as standard preformed implants or able to be individualized for the patient. The aim of this study was to analyze whether individualized orbital implants allow a more precise reconstruction of the orbit than standard preformed implants. MATERIALS AND METHODS A total of 195 patients treated between 2010 and 2014 were followed up to 12 weeks after surgery. Of the patients, 100 had received standardized preformed and 95 individualized implants. The precision of orbital reconstruction with the different implants was determined by comparing the variances in the volume difference between the reconstructed and the contralateral orbit on the postoperative computed tomographic scans. Clinical volume-related parameters including globe position, vision, motility, and diplopia and surgical details including approach, timing and technique of implant modification, use of navigation, duration of surgery, as well as adverse events were documented. RESULTS Orbital reconstruction was significantly more precise when individualized implants were used. The same was seen with intraoperative navigation. An overlap in the use of individualized implants and navigation makes it difficult to attribute the improved precision to a single factor. CONCLUSION This study demonstrated that individualization and navigation provide clinical benefit.

Additive effect of mesenchymal stem cells and VEGF to vascularization of PLGA scaffolds

Bone marrow derived mesenchymal stem cells (bmMSCs) are widely used for the generation of tissue engineering constructs, since they can differentiate into different cell types occurring in bone tissues. Until now their use for the generation of tissue engineering constructs is limited. All cells inside a tissue engineering construct die within a short period of time after implantation of the construct because vascularization and establishment of connections to the recipient circulatory system is a time consuming process. We therefore compared the influences of bmMSC, VEGF and a combination of both on the early processes of vascularization, utilizing the mice skinfold chamber model and intravital fluorescence microscopy. Tissue engineering constructs based on collagen coated Poly d,l-lactide-co-glycolide (PLGA) scaffolds, were either functionalized by coating with vascular endothelial growth factor (VEGF) or vitalized with bmMSC. PLGA without cells and growth factor was used as the control group. Functionalized and vitalized tissue engineering constructs showed an accelerated growth of microvessels compared to controls. Only marginal differences in vascular growth were detected between VEGF containing and bmMSC containing constructs. Constructs containing VEGF and bmMSC showed a further enhanced microvascular growth at day 14. We conclude that bmMSCs are well suited for bone tissue engineering applications, since they are a valuable source of angiogenic growth factors and are able to differentiate into the tissue specific cell types of interest. The dynamic process of vascularization triggered by growth factor producing cells can be amplified and stabilized with the addition of accessory growth factors, leading to a persisting angiogenesis, but strategies are needed that enhance the resistance of bmMSC to hypoxia and increase survival of these cells until the tissue engineering construct has build up a functional vascular system.

Putative CD133 + melanoma cancer stem cells induce initial angiogenesis in vivo

Tumor angiogenesis is essential for tumor growth and metastasis, and is regulated by a complex network of various types of cells, chemokines, and stimulating factors. In contrast to sprouting angiogenesis, tumor angiogenesis is also influenced by hypoxia, inflammation, and the attraction of bone-marrow-derived cells. Recently, cancer stem cells have been reported to mimic vascularization by differentiating into endothelial cells and inducing vessel formation. In this study, the influence of cancer stem cells on initial angiogenesis was evaluated for the metastatic melanoma cell line D10. Following flow cytometry, CD133+ and CD133- cells were isolated using magnetic cell separation and different cell fractions were transferred to porcine gelatin sponges, which were implanted into the dorsal skinfold chamber of immunocompromised mice. Angiogenesis was analyzed based on microvessel density over a 10-day period using in vivo fluorescence microscopy, and the results were verified using immunohistology. CD133+ D10 cells showed a significant induction of early angiogenesis in vivo, contrary to CD133- D10 cells, unsorted D10 cells, and negative control. Neovascularization was confirmed by visualizing endothelial cells by immunohistology using an anti-CD31 antibody. Because CD133+ cells are rare in clinical specimens and hardly amenable to functional assays, the D10 cell line provides a suitable model to study the angiogenic potential of putative cancer stem cells and the leukocyte-endothelial cell interaction in the dorsal skinfold chamber in vivo. This cancer stem cell model might be useful in the development and evaluation of therapeutic agents targeting tumors.

Heterotopic bone formation in the musculus latissimus dorsi of sheep using β-tricalcium phosphate scaffolds: evaluation of an extended prefabrication time on bone formation and matrix degeneration

We previously generated viable heterotopic bone in living animals and found that 3 months of intrinsic vascularization improved bone formation and matrix degeneration. In this study, we varied the pre-vascularization time to determine its effects on the kinetics of bone formation and ceramic degradation. Two 25-mm-long cylindrical β-tricalcium phosphate scaffolds were filled intraoperatively with autogenous iliac crest bone marrow and implanted in the latissimus dorsi muscle in six sheep. To examine the effect of axial perfusion, one scaffold was surgically implanted with (group C) or without (group D) a central vascular bundle. All animals were sacrificed 6 months postoperatively and histomorphometric measurements were compared to previous results. All implanted scaffolds exhibited ectopic bone growth. However, bone growth was not significantly different between the 3-month (group A, 0.191±0.097 vs. group C, 0.237±0.075; P=0.345) and 6-month (group B, 0.303±0.105 vs. group D, 0.365±0.258; P=0.549) pre-vascularization durations, regardless of vessel supply; early differences between surgically and extrinsically vascularized constructs disappeared after 6 months. Here, we describe a reliable procedure for generating ectopic bone in vivo. A 3-month pre-vascularization duration appears sufficient and ceramic degradation proceeds in accordance with bone generation, supporting the hypothesis of cell-mediated resorption.

Efficacy of transcutaneous transseptal orbital decompression in treating acute retrobulbar hemorrhage and a literature review.

Decreasing visual acuity secondary to orbital trauma may be caused by sudden space-occupying or expanding intraorbital lesions, including retrobulbar hemorrhage (RBH), herniation, or swelling. RBH must be diagnosed and treated immediately. This article addresses the efficacy of transcutaneous transseptal orbital decompression in a combination with a systematic review of the literature for a comparison of this method with existing treatment options. For this study the departments database was retrospectively screened for patients with acute RBH who were treated between 2009 and 2011 using the authors’ approach. Patients presenting with RBH were classified into RBH classes I to III according to three different clinical and radiological manifestations of acute RBH. The efficacy of transcutaneous transseptal orbital decompression was assessed by postoperative visual acuities. The literature review was performed by using the MEDLINE database. The time period for the study was between 2009 and 2011 during which 10 patients were diagnosed with suspected RBH and 9 were treated with the authors’ technique. Visual acuities were reconstituted or maintained in almost 86% of patients who were diagnosed and treated according to the authors approach and who survived initial trauma. It was concluded that transcutaneous transseptal orbital decompression provides an efficient and rapid approach for treating patients with acute RBH. By distinguishing three different manifestations of acute RBH, the authors present a diagnostic tool that may facilitate classification of RBH and determination of treatment options.

Diagnosis and treatment of optic nerve trauma.

Decreasing visual acuity secondary to orbital trauma or orbital and anterior skull base surgery may be caused by either sudden space-occupying intraorbital lesions, including retrobulbar hemorrhage (RBH), or direct damage to the prechiasmatic pathway. Contrary to traumatic optic neuropathy, RBH must be diagnosed and treated immediately to prevent permanent damage to the visual system. Therefore, monitoring and handling of visual pathway damage are mandatory. Flash visual evoked potentials and electroretinograms can provide evidence of the status of conductivity of the visual pathway when clinical assessment is not feasible. Both are thus essential diagnostic procedures not only for primary diagnosis but also for intraoperative evaluation. In case of RBH surgical decompression is compulsory. However, traumatic optic neuropathy does not respond to either corticosteroids or optic canal surgery. Modern craniomaxillofacial surgery requires detailed consideration of the diagnosis and treatment of traumatic visual pathway damage with the ultimate goal of preserving visual acuity.

In vivo tissue engineered bone versus autologous bone: stability and structure

This pilot study investigated the biomechanical properties of prefabricated, vascularized bioartificial bone grafts, which may provide an alternative bone source for the restoration of segmental osseous defects. Vascularized bioartificial bone grafts comprise an artificial customized scaffold made of beta-tricalcium phosphate. Bone formation along the prefabricated scaffold is induced by autogenous cancellous bone. Vascularization of the bone graft is provided by the hosts vascular system. Within 6 months, a mammalian bioreactor (sheep were used in the present study) creates heterotopic vascularized bioartificial bone grafts of a predetermined anatomical shape, which can be harvested for reconstructing osseous defects. The bioartificial bone grafts in this study contained up to 25% bone tissue, as shown by histomorphometric analysis and computed tomography. Moreover, unconfined compression tests revealed that the constructs had mechanical characteristics similar to those of ovine cancellous bone. Therefore, this method could be applied to generate vascularized prefabricated bone substitutes for critical-size defects.

Piezoelectric surgery and navigation: a safe approach for complex cases of Eagle syndrome

Eagle syndrome was first described by Eagle in 1937. It is associated with an elongated styloid process and/or calcification of the stylohyoid ligament, mainly resulting in pain in the orofacial region. The treatment of Eagle syndrome includes conservative treatment with physical therapy supported by medication, or surgical removal of the styloid process. Two different surgical approaches are described in the literature: the transoral and transcervical approaches. Both have their limitations and specific intraoperative risks. A modification of the transcervical approach that adds an extra security measure to the treatment of complex cases of Eagle syndrome is presented herein. The styloid process was removed by combining piezoelectric surgery, preoperative digital planning, and surgical navigation. No complication was noted, and the patient recovered quickly after surgery. A follow-up visit 2 months later showed no remaining symptoms of Eagle syndrome on the treated side. Therefore, digital planning and surgical navigation could add valuable safety measures to the treatment of complex cases of Eagle syndrome.

CD24 + tumor-initiating cells from oral squamous cell carcinoma induce initial angiogenesis in vivo

BACKGROUND In oral squamous cell carcinoma (OSCC), a minor subset of cancer stem cells has been identified using the surface marker CD24. The CD24+ cell population is involved in initiating, maintaining, and expanding tumor growth, but has not been reported to be involved in angiogenesis to date. METHODS NOD/SCID mice were equipped with dorsal skinfold chambers and gelatin sponges seeded with CD24+, CD24-, and unsorted cancer cells suspended in Matrigel® were implanted. Following intravital fluorescence microscopy, specimens were examined by immunohistology. RESULTS Sponges seeded with CD24+ cells showed a significantly higher functional capillary density than those seeded with CD24- cells. The presence of endothelial cells was confirmed by immunohistochemistry for CD31. CONCLUSION For the first time, CD24+ tumorigenic cells with angiogenic potential, which were isolated from OSCC, were characterized. Our findings provide a promising in vivo model to facilitate the development of therapeutic agents against cancer stem cells and their angiogenic pathways.

A new concept for implant-borne dental rehabilitation; how to overcome the biological weak-spot of conventional dental implants?

BackgroundEvery endosseous dental implant is dependent on an adequate amount and quality of peri-implant hard and soft tissues and their fully functional interaction. The dental implant could fail in cases of insufficient bone and soft tissues or due to a violation of the soft to hard tissues to implant shoulder interface with arising of a secondary bone loss.MethodTo overcome this biological weak-spot, we designed a new implant that allows for multi vector endosseous anchorage around the individual underlying bone, which has to be scanned by computed tomography (CT) or Cone beam CT (CBCT) technique to allow for planning the implant. We developed a workflow to digitally engineer this customized implant made up of two planning steps. First, the implant posts are designed by prosthodontic-driven backward planning, and a wireframe-style framework is designed on the individual bony surface of the recipient site. Next, the two pieces are digitally fused and manufactured as a single piece implant using the SLM technique (selective laser melting) and titanium-alloy-powder.ResultsPreoperative FEM-stress-test of the individual implant is possible before it is inserted sterile in an out-patient procedure.ConclusionUnlike any other historical or current dental implant protocol, our newly developed “individual patient solutions dental” follows the principle of a fully functional and rigid osteosynthesis technology and offers a quick solution for an implant-borne dental rehabilitation in difficult conditions of soft and hard tissues.