Jonas Lorenz

Potential lack of “standardized” processing techniques for production of allogeneic and xenogeneic bone blocks for application in humans

In the present study, the structure of two allogeneic and three xenogeneic bone blocks, which are used in dental and orthopedic surgery, were histologically analyzed. The ultimate goal was to assess whether the components postulated by the manufacturer can be identified after applying conventional histological and histochemical staining techniques. Three samples of each material, i.e. allogeneic material-1 and -2 as well as xenogeneic material-1, -2 and -3, were obtained commercially. After decalcification and standardized embedding processes, conventional histological staining was performed in order to detect inorganic matrix, cellular or organic matrix components. Allogeneic material-1 showed trabecular bone-like structures, which were free of cellular components as well as of organic matrix. The allogeneic material-2 showed trabecular bone structures, in which connective tissue and cellular remnants were embedded. Additionally, some connective tissue, which resembled fat-like tissue, was found within this material. The xenogeneic material-1 showed trabecular bone-like structures and contained organic components comparable to that demonstrated for the allogeneic material-2. The xenogeneic material-2 showed trabecular bone structures with single cells located in lacunae. The xenogeneic material-3 also showed trabecular structures. Neither cellular nor organic matrix components were found within this material. According to the data of the present study, the allogeneic material-1 and the xenogeneic material-3 were the only investigated materials for which the obtained histological data were in accordance with the manufactureŕs advertised information. The remaining three materials showed discrepancies-although the manufacturers of all five bone substitute materials stated that their blocks were free of organic/cellular remnants. These data are of great clinical and material science interest. It seems that even patented processing techniques are not always able to deliver reproducible materials. Although the manufacturers of all five bone blocks stated that their blocks were free of organic/cellular remnants, our histological analysis revealed that three out of five bone blocks did contain such remnants. Such specimens might be able to induce an immune response within the recipient.

Bilayered, non-cross-linked collagen matrix for regeneration of facial defects after skin cancer removal: a new perspective for biomaterial-based tissue reconstruction

Classically skin defects are covered by split thickness skin grafts or by means of local or regional skin flaps. In the presented case series for the first time a bilayered, non-crossed-linked collagen matrix has been used in an off-label fashion in order to reconstruct facial skin defects following different types of skin cancer resection. The material is of porcine origin and consists of a spongy and a compact layer. The ratio of the two layers is 1:3 in favour of the spongy layer. The aim of the study was to investigate the potential of this matrix for skin regeneration as an alternative to the standard techniques of skin grafts or flaps. Six patients between 39 and 83xa0years old were included in the study based on a therapeutic trial. The collagen matrix was used in seven defects involving the nose, eyelid, forehead- and posterior scalp regions, and ranging from 1,2 to 6xa0cm in diameter. Two different head and neck surgeons at two different institutions performed the operations. Each used a different technique in covering the wound following surgery, i.e. with and without a latex-based sheet under the pressure dressing. In three cases cylindrical biopsies were taken after 14xa0days. In all cases the biomaterial application was performed without any complication and no adverse effects were observed. Clinically, the collagen matrix contributed to a tension-free skin regeneration, independent of the wound dressing used. The newly regenerated skin showed strong similarity to the adjacent normal tissue both in quality and colour. Histological analysis indicated that the spongy layer replaced the defective connective tissue, by providing stepwise integration into the surrounding implantation bed, while the compact layer was infiltrated by mononuclear cells and contributed to its epithelialization by means of a „conductive“process from the surrounding epithelial cells. The clinical and histological data demonstrate that the collagen bilayered matrix used in this series contributes to a „Guided-Integrative-Regeneration-Process“, which still needs to be further understood. The biomimetic nature of this material seems to contribute to physiological matrix remodelling, which probably involves other matricellular proteins essential for soft tissue regeneration. A deeper understanding of the mechanism, involved in the tissue integration of this material and its contribution to soft tissue regeneration based on the direct and indirect effect of matricellular proteins could open new therapeutic avenues for biomaterial-based soft tissue regeneration as an alternative to traditional flap-based plastic surgery.

Expansion of the peri-implant attached gingiva with a three-dimensional collagen matrix in head and neck cancer patients—results from a prospective clinical and histological study

ObjectivesAttached peri-implant gingiva has proven to have an influence on the long-term stability of dental implants. In patients with head and neck cancer, a functional peri-implant gingiva is even more of critical importance. The aim of the presented prospective study was to investigate a three-dimensional xenogeneic collagen matrix for augmentation around dental implants in patients with former head and neck cancer.Material and methodsEight patients presenting with insufficient peri-implant gingiva underwent vestibuloplasty on 51 implants using a xenogeneic collagen matrix. The clinical performance and the shrinking tendency of the matrix were analyzed in a cohort study. Furthermore, eight biopsies from the augmented regions were examined histologically to determine the biomaterial-related tissue reaction.ResultsInitially after vestibuloplasty, a mean width of attached gingiva of 4.4u2009±u20090.94xa0mm could be achieved. At clinical follow up investigation 6xa0months after vestibuloplasty, a mean width of 3.9u2009±u20090.65xa0mm attached peri-implant gingiva with a mean shrinking tendency of 14xa0% could be detected. Histological analysis of the biopsies revealed a well integrated collagen22 matrix covered with epithelium. Within the compact layer, mononuclear cells were observed only, while the spongious layer was infiltrated with a cell-rich connective tissue.ConclusionWithin its limits, the presented study revealed that the investigated collagen matrix is suitable to enlarge the peri-implant attached gingiva in head and neck cancer patients without adverse reactions or a multinucleated giant cell-triggered tissue reaction.Clinical relevanceThe application of the investigated three-dimensional collagen matrix in vestibuloplasty achieved a sufficient amount of peri-implant attached gingiva in head and neck cancer patients. The favorable tissue reaction and the low shrinking tendency make the collagen matrix a promising alternative to autologous tissue grafts.

Fifteen years of platelet rich fibrin (PRF) in dentistry and oromaxillofacial surgery: How high is the level of scientific evidence?

Platelet-rich fibrin is a blood concentrate system used for soft tissue and bone tissue regeneration. In the last decade, platelet rich fibrin (PRF) has been widely used in different indication fields, particularly in oral and maxillofacial surgery. This review investigates the level of scientific evidence of published articles related to the use of PRF for bone and soft tissue regeneration in dentistry and maxillofacial surgery. An electronic literature research using the biomedical search engine National Library of Medicine (PubMed-MEDLINE) was performed in May 2017. A total of 392 articles were found, 72 of which were classified for each indication field. When comparing PRF with biomaterials vs biomaterial alone in sinus lift (5 studies; IIa), no statistically significant differences were detected. Socket preservation and ridge augmentation using PRF significantly enhanced new bone formation compared to healing without PRF (7 studies Ib, IIa, IIb). Reepithelialization and bone regeneration was achieved in 96 of 101 patients diagnosed with medication-related osteonecrosis of the jaw (5 studies, III). In periodontology, PRF alone (6 studies; Ib, IIa, IIb) or its combination with biomaterials (6 studies; Ib, IIa, IIb) significantly improved the pocket depth and attachment loss compared to a treatment without PRF. Over 70% of the patients were part of studies with a high level of scientific evidence (randomized and controlled prospective studies). This published evidence (38 articles), with a high scientific level, showed that PRF is a beneficial tool that significantly improves bone and soft tissue regeneration. However, the clinical community requires a standardization of PRF protocols to further examine the benefit of PRF in bone and soft tissue regeneration in reproducible studies, with a higher scientific level of evidence.

Do Clinical and Radiological Assessments Contribute to the Understanding of Biomaterials? Results From a Prospective Randomized Sinus Augmentation Split-Mouth Trial

The present prospective randomized split-mouth trial reports on the 3-year clinical and radiological follow-up investigation of implants placed 7 months after sinus augmentation with 2 different bone substitute materials. The aim of the study was to complete the histologic observation of cellular reactions by analyses of the implants and the volumetric changes of the augmented bone substitute materials. A sinus augmentation split-mouth trial was performed in 14 patients with the synthetic bone substitute material Nanobone (NB) and the xenogeneic Bio-Oss (BO). Changes in volume and density of the augmented biomaterials were investigated by analysis of computed tomography scans, taken immediately after augmentation and after 7 months. Clinical implant parameters were assessed after 3 years of loading. Both bone substitute materials underwent nonsignificant volume reduction and significant increase in bone density over an integration period of 7 months. No significant differences concerning volume and bone density were observed between the groups. Three years after loading, 51 of 53 implants were in situ with no peri-implant infections, and only a few soft-tissue variations were present. The present prospective randomized study showed that no differences could be observed clinically and radiologically. Accordingly, it seems that both biomaterials, independent of their physicochemical composition, enable clinical success and long-time stability for dental implants. Interestingly, the histological results showed distinct differences in cellular reactions: While the xenogeneic BO induced a mild tissue reaction with only few multinucleated giant cells and comparably low vascularization, the synthetic NB induced a multinucleated giant cell-triggered tissue reaction with an increase of vascularization. Thus, the present study showed that a combination analysis-histological, clinical, and radiological-is necessary for a detailed assessment of a biomaterials quality for clinical application.

Individualized titanium mesh combined with platelet-rich fibrin and deproteinized bovine bone: A new approach for challenging augmentation

Autologous bone transfer is regarded as the gold standard for ridge augmentation before dental implantation, especially in severe bony defects caused by tumor resection or atrophy. In addition to the advantages of autologous bone, transplantation has several disadvantages, such as secondary operation, increased morbidity and pain. The present study reports, for the first time, a combination of a xenogeneic bone substitute (BO) with platelet-rich fibrin (PRF), which is a fully autologous blood concentrate derived from the patients own peripheral blood by centrifugation. Solid A-PRF+ and liquid i-PRF together with an individualized 3-D planned titanium mesh were used for reconstruction of a severe tumor-related bony defect within the mandible of a former head and neck cancer patient. The BO enriched with regenerative components from PRF allowed the reconstruction of the mandibular resective defect under the 3-D mesh without autologous bone transplantation. Complete rehabilitation and restoration of the patients oral function were achieved. Histological analysis of extracted bone biopsies confirmed that the new bone within the augmented region originated from the residual bone. Within the limitations of the presented case, the applied concept appears to be a promising approach to increase the regenerative capacity of a bone substitute material, as well as decrease the demand for autologous bone transplantation, even in cases in which autologous bone is considered the golden standard. PRF can be considered a reliable source for increasing the biological capacities of bone substitute materials.

Screw-retained monolithic zirconia vs. cemented porcelain-fused-to-metal implant crowns: a prospective randomized clinical trial in split-mouth design

ObjectivesThe objective of the present study was to compare the clinical performance of screw-retained, monolithic, zirconia, and cemented porcelain-fused-to-metal (PFM) implant crowns.Materials and methodsIn a prospective, randomized, clinical, split-mouth trial, 22 patients’ bilateral premolar or molar single-gap were restored with either screw-retained (test group) or cemented supraconstruction (control group). Clinical parameters, soft-tissue health, crestal bone-level changes, technical complications, and patient’s subjective feelings were recorded during a follow-up period of 12xa0months.ResultsNo implant was lost during the follow-up period. Of the crowns, 4.5% (test) and 9.1% (control) showed bleeding on probing (Pu2009=u20091.000), and plaque was visible in 13.6% (test) and 27.3% (control) of the crowns (Pu2009=u20090.240). Changes in bone crest level seemed to have no correlation with the restoration method (Pu2009=u20090.77/0.79). Technical failures were observed in three restorations of the test and four of the control group. Evaluation of patients’ satisfaction revealed high acceptance regarding fit, esthetics, and chewing effectiveness in both groups.ConclusionOver a 12-month follow-up, screw-retained and cemented crowns could show comparable clinical and radiological results regarding soft tissue health, marginal bone level, and patient satisfaction. Duration of treatment alone was significantly shorter in screw-retained crowns.Clinical relevanceProsthetic retention methods are related with the occurrence of complications, such as peri-implantitis. However, scientific valuable data that proof superiority of a specific retention technique are rare. In single-gap implants, screw retention and cementation seemed to achieved comparable results.

Allogeneic bone block for challenging augmentation—a clinical, histological, and histomorphometrical investigation of tissue reaction and new bone formation

ObjectivesThe aim of the present study was the histological investigation of an allogeneic spongious bone block for horizontal and vertical ridge augmentation in humans. The amount of new bone, soft tissue, and residual bone substitute were histomorphometrically assessed after a mean healing period of 6xa0months.Materials and methodsFourteen patients received augmentation with an allogeneic spongious bone block (Tutobone®, Tutogen Medical, Neunkirchen, Germany). After 6xa0months of healing, 28 implants were placed with simultaneous harvesting of bone biopsies for histological and histomorphometrical analysis. Moreover, samples from the bone blocks were collected as blanks and analyzed histologically. The formation of new bone, connective tissue, and remaining bone substitute material as well as vascularization and formation of multinucleated giant cells (MNCGs) within the augmentation bed were analyzed.ResultsNew bone formation could be observed primarily in close proximity to the bone block. Histomorphometrical analyses showed 18.65u2009±u200912.20% newly formed bone, 25.93u2009±u200912.36% allogeneic spongious bone block, and 53.45u2009±u200910.34% connective tissue. MNCGs were observed on the biomaterial surface. Furthermore, organic residues were evident, as donor-related cellular remnants within the osteocyte lacunae were found in the blank bone blocks and in the analyzed biopsies.ConclusionDespite the presence of donor-related organic remnants, the bone block shows the ability to serve as a scaffold for new bone formation. Within the limits of the present study, the detect organic remnants seemed not to affect the bone formation or influence the host in the long term.Clinical relevanceClinicians have to make a conscious choice of the applied biomaterials with regard to their components and structure to support tissue regeneration and maintain patient safety.

Investigation of peri-implant tissue conditions and peri-implant tissue stability in implants placed with simultaneous augmentation procedure: a 3-year retrospective follow-up analysis of a newly developed bone level implant system

BackgroundGuided bone regeneration (GBR) has been proven to be a reliable therapy to regenerate missing bone in cases of atrophy of the alveolar crest. The aim of the present retrospective analysis was to assess peri-implant tissue conditions and document peri-implant tissue stability in C-Tech implants when placed simultaneously with a GBR augmentation procedure.MethodsA total of 47 implants, which were placed simultaneously with a GBR procedure with a synthetic bone substitute material in 20 patients, were investigated clinically and radiologically at least 3xa0years after loading. Implant survival, the width and thickness of peri-implant keratinized gingiva, probing depth, bleeding on probing (BOP), the Pink Esthetic Score (PES), peri-implant bone loss, and the presence of peri-implant osteolysis were determined.ResultsThe follow-up investigation revealed a survival rate of 100% and only low median rates for probing depths (2.7xa0mm) and BOP (30%). The mean PES was 10.1 from the maximum value of 14. No osseous peri-implant defects were obvious, and the mean bone loss was 0.55xa0mm.ConclusionsIn conclusion, implants placed in combination with a GBR procedure can achieve long-term stable functionally and esthetically satisfying results for replacing missing teeth in cases of atrophy of the alveolar crest.

Volumetric analysis of bone substitute material performance within the human sinus cavity of former head and neck cancer patients: A prospective, randomized clinical trial

Background: In numerous animal and human studies, it could be detected that in bone augmentation procedures, materials physicochemical characteristics can influence the cellular inflammatory pattern and therefore the integration in the host tissue. Histological, histomorphometrical, and clinical analyses of the integration of the biomaterial in the surrounding tissue are well established methodologies; however, they do not make a statement on volume and density changes of the augmented biomaterial. Aims: The aim of the present study was to assess the volume and density of a xenogeneic (Bio-Oss®, BO) and a synthetic (NanoBone®, NB) bone substitute material in split-mouth sinus augmentations in former tumor patients to complete histological and histomorphometrical assessment. Methods: Immediately and 6 months after sinus augmentation computed tomography scans were recorded, bone grafts were marked, and the volume was calculated with radiologic RIS-PACS software (General Electric Healthcare, Chalfont St. Giles, Great Britain) to determine the integration and degradation behavior of both biomaterials. Results: Radiographic analysis revealed a volume reduction of the initial augmented bone substitute material (i.e. 100%) to 77.36 (±11.68) % in the BO-group, respectively, 75.82 (±22.28) % in the NB-group six months after augmentation. In both materials, the volume reduction was not significant. Bone density significantly increased in both groups. Conclusion: The presented radiological investigation presents a favorable method to obtain clinically relevant information concerning the integration and degradation behavior of bone substitute materials.