OBJECTIVE This study aims to validate the standardized procedure for designing soft tissue substitutes (STS) adapted to optimally fit single-tooth defects in the anterior jaws and double-tooth defects in the posterior jaw and to compare mathematically modeled average shapes. MATERIALS AND METHODS Casts from 35 patients with 17 single-tooth defects in anterior region and 21 double-tooth defects in posterior region were scanned. STS were designed and sectioned in 3D slices meshes. Thickness values were documented respecting mesial-distal and buccal-lingual orientations. Graphs were embedded into images, and hierarchical clustering was applied to group STS according to shape and thickness. RESULTS STS clustered into two groups per defect type. For anterior single defects, STS (n = 4) were either a small and thin oval: 7 mm buccal-lingual, 4-5 mm mesial-distal direction and 1.1-1.5 mm thick or a larger oval (n = 13): 9 mm buccal-lingual, 5-7 mm mesial-distal and 1.6 m thick. For posterior double tooth defects, STS (n = 10) were either narrow, long and thick: 6-7 mm buccal-lingual, 16-20 mm mesial-distal and 2.2 thick or a wide, thinner rectangle (n = 11): 9-11 mm buccal-lingual, 12-14 mm mesial-distal and 1.1-1.5 mm thick. CONCLUSIONS The study validated the standardized digital method to design grafts for soft tissue volume augmentation and identified four average shapes for anterior single-tooth and posterior double-tooth soft tissue defects. CLINICAL SIGNIFICANCE We developed and validated a standardized digital method to design an optimal geometrical shape of a soft tissue substitute for oral volume augmentation and combined it with mathematical modeling to identify average shapes for single-interior, and double-posterior tooth defects. The identified average shapes offer the possibility to produce better-fitted xenografts or synthetic STS blocks requiring minimal chair-side adaptation leading to reduced clinical time and patient discomfort and potentially improving soft tissue volume augmentation outcomes.

Background Common in vitro cell culture systems for testing implant material immune-compatibility either employ immortal human leukocyte cell lines or use isolated primary cells. Compared to in vivo conditions, this generates an environment of substantially reduced complexity, often lacking important immune cell types, such as neutrophil granulocytes and others. This paper describes an innovative human whole blood culture model for in vitro testing of implant materials under in vivo -like conditions. The major goal of this culture model was to maintain as much of the naturally inherent complexity of immune cell interactions as possible and to avoid errors often caused by stressful conditions during cell preparation. Methods A closed, CO 2 -independent, tube-based culture vessel was used, containing one milliliter of freshly drawn human blood for each sample. The cultures were occasionally rotated to increase immune cell contacts with the test materials. Immune cell responses were examined by multiplexed cytokine analysis. Results Three different types of commercially available implant materials i.e. barrier membranes, used for dental, trauma and maxillofacial surgery, were examined for their potential interactions with immune cells. The barrier membranes were either of synthetic (i.e. the polymers polytetrafluoroethylene, PTFE, and polycaprolactone, PCL), or of natural origin (porcine collagen membrane). The results identified characteristic differences in the overall activity profiles with very low immune cell responses for PTFE, intermediate ones for collagen, and strong reactions towards PCL. Conclusions This innovative human whole blood in vitro model, using a complex, organotypic matrix and all immune cells available in peripheral blood, is an excellent, easy to standardize tool to categorize immune cell responses to implant materials. Compared to in vitro cell culture systems used for material research, this new assay system provides a far more detailed picture of response patterns the immune system is able to develop when interacting with different types of materials and surfaces.

Three-dimensional (3D) printing technology allows the production of an individualized 3D object based on a material of choice, a specific computer-aided design and precise manufacturing. Developments in digital technology, smart biomaterials and advanced cell culturing, combined with 3D printing, provide promising grounds for patient-tailored treatments. In dentistry, the “digital workflow” comprising intraoral scanning for data acquisition, object design and 3D printing, is already in use for manufacturing of surgical guides, dental models and reconstructions. 3D printing, however, remains un-investigated for oral mucosa/gingiva. This scoping literature review provides an overview of the 3D printing technology and its applications in regenerative medicine to then describe 3D printing in dentistry for the production of surgical guides, educational models and the biological reconstructions of periodontal tissues from laboratory to a clinical case. The biomaterials suitable for oral soft tissues printing are outlined. The current treatments and their limitations for oral soft tissue regeneration are presented, including “off the shelf” products and the blood concentrate (PRF). Finally, tissue engineered gingival equivalents are described as the basis for future 3D-printed oral soft tissue constructs. The existing knowledge exploring different approaches could be applied to produce patient-tailored 3D-printed oral soft tissue graft with an appropriate inner architecture and outer shape, leading to a functional as well as aesthetically satisfying outcome.

Background: Soft tissue augmentation is necessary to regain reduced or lost tissue in edentulous patients. Autologous soft tissue grafts are the gold standard despite drawbacks: limited tissue availability, invasive surgical procedure, and patient pain/discomfort. Moreover, different geometries of individual tooth defects require chair-side graft shaping prior application. To avoid complications at the donor site, xenogenic and allogenic matrices were developed. However, they also need shape adjustments. Aim/Hypothesis: This study aimed to develop a standardized procedure for designing average grafts adapted to optimally fit the common single-tooth soft tissue defects in the posterior jaw region. Materials and Methods: Casts from 33 patients with single tooth defects in the posterior region of the upper and lower jaws were collected and scanned. The grafts were designed with the 3Shape dental designer based on an incision line placed 1.5 mm away from adjacent teeth and extended 4 mm down to the vestibular side. A systematic procedure was developed using GOM inspect software to standardize the measurements across all grafts. The occlusal, mesial-distal and buccal-lingual planes were defined to section the graft, and each graft was represented as a mesh of 1 mm3 cubes. The thickness values of each cube were documented in a coordinate system chart with the corresponding mesial-distal and buccal-lingual orientations. Orange software was applied on each sample to generate a “bubble” graph depicting thickness, shape and dimension of the graft. The “complete” hierarchical clustering workflow was applied to group the grafts. For each group, median thickness was calculated to obtain an average shape. Results: Based on shapes, the designed grafts were clustered into three groups. Two types of average graft shapes could be distinguished for the upper jaw defects. The first graft (n = 13) had a square shape with average dimensions of 10 mm in a lingual-buccal and 7–10 mm in a mesial-distal direction. The second graft shape (n = 11) was longer (11 mm lingual-buccal) and narrower (4–7 mm mesial-distal). The average graft shape for lower jaw defects (n = 9) was smaller and different compared to the upper jaw average graft shapes. The lingual-buccal dimension was 6–8 mm and mesial-distal in a range of 5–10 mm. Regarding the thickness, all three average graft shapes had the highest thickness in the middle portion, above the alveolar ridge region, with mean values around 2 mm. The graft thickness decreased gradually in the buccal and palatal/lingual directions towards the margin, where the lowest thickness at specific points was below 0.2 mm. Conclusions and Clinical Implications: The study demonstrates the proof of concept approach to design average shape grafts for soft-tissue augmentation of single-tooth defects in the posterior jaw region. Application of prefabricated xenogenic and allogenic matrices in shapes adapted to the geometry of most common soft tissue defects will bring accuracy for required augmentation and reduce surgical time. Future work aims at confirming the obtained average shapes with more samples, and design average shapes for other defect types. Keywords: Soft tissue augmentation, Digital design, Single-tooth defect, Novel graft shape.

Objective: Successful repair of defects in the avascular zone of meniscus remains a challenge in orthopedics. This proof of concept study aimed to investigate a guided tissue regeneration approach for treatment of tears in meniscus avascular zone in a goat model. Design: Full-depth longitudinal tear was created in the avascular zone of the meniscus and sutured. In the two treatment groups, porcine collagen membrane was wrapped around the tear without (CM) or with injection of expanded autologous chondrocytes (CM+cells), whereas in the control group the tear remained only sutured. Gait recovery was evaluated during the entire follow-up period. On explantation at 3 and 6 months, macroscopic gross inspection assessed healing of tears, degradation of collagen membrane, potential signs of inflammation, and osteoarthritic changes. Microscopic histology scoring criteria were developed to evaluate healing of tears, the cellular response, and the inflammatory response. Results: Gait recovery suggested protective effect of collagen membrane and was supported by macroscopical evaluation where improved tear healing was noted in both treated groups. Histology scoring in CM compared to suture group revealed an increase in tear margins contact, newly formed connective tissue between margins, and cell formations surrounded with new matrix after 3 months yet not maintained after 6 months. In contrast, in the CM+cells group these features were observed after 3 and 6 months. Conclusions: A transient, short-term guided tissue regeneration of avascular meniscal tears occurred upon application of collagen membrane, whereas addition of expanded autologous chondrocytes supported more sustainable longer term tear healing.

OBJECTIVES:The objective of this study was to develop a 3D bone chip organ culture model. We aimed to collect in vitro evidence of the ability of vital bone chips to promote new bone formation.MATERIALS AND METHODS:We developed a 3D in vitro hypoxic bone chip organ culture model. Histology of the bone chips was performed before and after culture and immunohistochemistry after 3-week culture. The 3D culture supernatants were tested for the presence of pro-angiogenic growth factors, TGFβ1, GADPH, bone alkaline phosphatase, osteocalcin, osteonectin, osteopontin, bone sialoprotein and collagen type I.RESULTS:Histology after culture revealed bone chips in a matrix of fibrin remnants and a fibrous-appearing matter. Collagen type I- and IV-positive structures were also identified. Cells could be seen on the surface of the bone chips, with spindle-shaped cells bridging the bone chip particles. Pro-angiogenic growth factors and TGFβ1were detected in the 3D cell culture supernatants. The transcripts for osteocalcin, bone sialoprotein and collagen type I were revealed only via PCR.CONCLUSIONS:Our results indicate that bone chips in our 3D organ culture remain vital and may stimulate the growth of a bone-forming matrix.CLINICAL RELEVANCE:The use of autogenous bone chips for oral and maxillofacial bone augmentation procedures is widespread in clinical practice. The rationale for this is that if bone chips remain vital in vivo, they could provide an environment promoting new bone formation through growth factors and cells. This 3D culture method is an essential tool for investigating the behaviour of bone chips.