Towards optimized tissue regeneration: a new 3D printable bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate.

Introduction: Autologous platelet concentrate (APC) are pro-angiogenic and can promote wound healing and tissue repair, also in combination with other biomaterials. However, challenging defect situations remain demanding. 3D bioprinting of an APC based bioink encapsulated in a hydrogel could overcome this limitation with enhanced physio-mechanical interface, growth factor retention/secretion and defect-personalized shape to ultimately enhance regeneration. Methods: This study used extrusion-based bioprinting to create a novel bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate. Chemico-physical testing exhibited an amorphous structure characterized by high shape fidelity. Cytotoxicity assay and incubation of human osteogenic sarcoma cells (SaOs2) exposed excellent biocompatibility. enzyme-linked immunosorbent assay analysis confirmed pro-angiogenic growth factor release of the printed constructs, and co-incubation with HUVECS displayed proper cell viability and proliferation. Chorioallantoic membrane (CAM) assay explored the pro-angiogenic potential of the prints in vivo. Detailed proteome and secretome analysis revealed a substantial amount and homologous presence of pro-angiogenic proteins in the 3D construct. Results: This study demonstrated a 3D bioprinting approach to fabricate a novel bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate with high shape fidelity, biocompatibility, and substantial pro-angiogenic properties. Conclusion: This approach may be suitable for challenging physiological and anatomical defect situations when translated into clinical use.

The Perfect Timing-Immediate versus Delayed Microvascular Reconstruction of the Mandible.

In this retrospective study, the clinical and economic implications of microvascular reconstruction of the mandible were assessed, comparing immediate versus delayed surgical approaches. Utilizing data from two German university departments for oral and maxillofacial surgery, the study included patients who underwent mandibular reconstruction following continuity resection. The data assessed included demographic information, reconstruction details, medical history, dental rehabilitation status, and flap survival rates. In total, 177 cases (131 male and 46 females; mean age: 59 years) of bony free flap reconstruction (72 immediate and 105 delayed) were included. Most patients received adjuvant treatment (81% with radiotherapy and 51% combined radiochemotherapy), primarily for tumor resection. Flap survival was not significantly influenced by the timing of reconstruction, radiotherapy status, or the mean interval (14.5 months) between resection and reconstruction. However, immediate reconstruction had consumed significantly fewer resources. The rate of implant-supported masticatory rehabilitation was only 18% overall. This study suggests that immediate jaw reconstruction is economically advantageous without impacting flap survival rates. It emphasizes patient welfare as paramount over financial aspects in clinical decisions. Furthermore, this study highlights the need for improved pathways for masticatory rehabilitation, as evidenced by only 18% of patients with implant-supported dentures, to enhance quality of life and social integration.

Platelet-rich fibrin for rehydration and pre-vascularization of an acellular, collagen membrane of porcine origin.

OBJECTIVES: Pre-vascularization of the collagen membranes with autologous platelet concentrates is a standard procedure in oral and maxillofacial surgery. This study analyzed the possible interaction of an acellular collagen membrane of porcine origin (NM) with platelet-rich fibrin (PRF) regarding its rehydration protocol with differences in pH values and effect on angiogenesis. MATERIALS AND METHODS: NM was analyzed alone and combined with solid PRF by plotting or co-culturing with injectable PRF. Different media (venous blood, buffer solution with a fixed pH value of 7, saline solution, and injectable PRF) were used to analyze the influence on pH value during rehydration. Chorion allantois membrane assay (CAM) was applied to check pro-angiogenic effects after 24, 48, and 72 h, followed by immunohistochemical analysis. RESULTS: Rehydration in injectable PRF showed acidity over time (p < 0.05). A definite pro-angiogenic effect of NM alone was found regarding neo-vessel formation supported by the respective light microscopically analysis without significant differences to PRF alone (p > 0.005). This pro-angiogenic effect could not be exaggerated when NM was combined with liquid/solid PRF (each p > 0.005). CONCLUSIONS: Rehydration with liquid PRF of the collagen membrane results in acidity compared to a saline solution or patient's blood. The significant pro-angiogenic potential of the membrane alone resulted in enhanced neo-vessel formation that could not be optimized with the addition of PRF. CLINICAL RELEVANCE STATEMENT: Using injectable PRF for rehydration protocol of the collagen membrane leads to acidosis that can ultimately optimize wound healing. Differences in the physio-mechanical interplay of collagen matrices and autologous platelet concentrates must result in clinical algorithms if pre-vascularization can maximize outcomes.

The Impact of Transfer-Related Ischemia on Free Flap Metabolism and Electrolyte Homeostasis-A New In Vivo Experimental Approach in Pigs.

Free flap tissue transfer represents the gold standard for extensive defect reconstruction, although malperfusion due to thrombosis remains the leading risk factor for flap failure. Recent studies indicate an increased immune response and platelet activation in connection with pathologic coagulation. The underlying cellular and molecular mechanisms remain poorly understood, however. The presented study, therefore, aims to investigate if transfer-related ischemia alters intra-flap metabolism and electrolyte concentrations compared to central venous blood after free flap transfer in pigs to establish a novel experimental model. Free transfer of a myocutaneous gracilis flap to the axillary region was conducted in five juvenile male pigs. The flap artery was anastomosed to the axillary artery, and intra-flap venous blood was drained and transfused using a rubber-elastic fixed intravenous catheter. Blood gas analysis was performed to assess the effect of transfer time-induced ischemia on intra-flap electrolyte levels, acid-base balance, and hemoglobin concentrations compared to central venous blood. Time to flap reperfusion was 52 ± 10 min on average, resulting in a continuous pH drop (acidosis) in the flaps' venous blood compared to the central venous system (p = 0.037). Potassium (p = 0.016), sodium (p = 0.003), and chloride (p = 0.007) concentrations were significantly increased, whereas bicarbonate (p = 0.016) and calcium (p = 0.008) significantly decreased within the flap. These observations demonstrate the induction of anaerobic glycolysis and electrolyte displacement resulting in acidosis and hence significant tissue damage already after a short ischemic period, thereby validating the novel animal model for investigating intra-flap metabolism and offering opportunities for exploring various (immuno-) thrombo-hemostatic issues in transplantation surgery.

Evaluation of the clinical safety and performance of a narrow diameter (2.9 mm) bone-level implant: a 1-year prospective single-arm multicenter study.

PURPOSE: Narrow-diameter implants facilitate single-tooth restoration when interdental or inter-implant spaces and bone volume are inadequate for using standard diameter implants. This study reports the short-term data on the clinical safety and performance of a bone-level-tapered two-piece implant with a 2.9 mm diameter in the clinical practice setting. This study was retrospectively registered on March 1st, 2016 (NCT02699866). METHODS: Implants were placed in partially healed extraction sockets of the central and lateral incisors in the mandible and lateral incisors in the maxilla for single-tooth replacement. The primary outcome was to assess implant survival at 12 months after placement. Secondary outcomes included implant success, pink esthetic score, marginal bone-level changes, and safety. RESULTS: Twenty four males and 17 females with a mean age of 44.5 (± 18.3 standard deviation) received the implant. Three out of 41 implants were lost yielding a survival rate of 92.7% (95%-CI: 79.0%; 97.6%) at 1 year. One patient reported an ongoing foreign body sensation, pain, and/or dysesthesia at month 12. The average pink esthetic score at 6 months was 11.2 (95%-CI: 10.5; 11.9). The bone level was stable with a mean bone-level change of-0.3 mm (± 0.42 mm standard deviation) at 1 year after implantation. No serious adverse events or adverse device events were reported. CONCLUSIONS: The use of a 2.9 mm diameter bone-level-tapered implant is a safe and reliable treatment option for narrow tooth gaps at the indicated locations. Overall performance and good survival rates support their use in cases, where wider implants are unsuitable.

A novel alloplastic grid reconstruction plate for the mandible - Retrospective comparative clinical analysis of failure rates and specific complications.

PURPOSE: This study aimed to investigate the effect of three different osteosynthesis plate systems on failure rates and complications after continuity-interrupting mandibular resections with alloplastic reconstructions. MATERIALS AND METHODS: Records of respective patients from 2010 to 2020 were analyzed retrospectively. The analyses included the osteosynthesis plate type (2.4 MANDIBULAR (RP1: MANDIBULAR [Medicon®, Tuttlingen, Germany]; RP2: Modus® Reco 2.5 [Medartis®, Basel, Switzerland]; and RP3: Modus 2 Mandible [Medartis®, Basel, Switzerland]), extent & location of the defect, age, sex, radiotherapy, and nicotine abuse. In case of failure, timepoint, and the problem, namely oral/extraoral dehiscence, screw loosening, and plate fractures that led to removal, were analyzed. Complications were classified according to Clavien-Dindo system. RESULTS: A total of 136 patients were included. The mean follow-up time was 18 ± 26 months. Survival rates after 1, 2, and 5 years were 69.9%, 66.9%, and 64.7%, respectively. Although survival was not significantly associated with the reconstruction system, the most frequent complications were seen in cases of RP1 & RP2 when compared to RP3 (p = 0.033). In brief, dehiscences were seen significantly less often in cases of RP3 (12.5%) when compared to RP1 (44.7%) and RP2 (26.9%; p = 0.024). Fractures of the osteosynthesis systems occurred in 3 of 4 cases (75%) with RP1, in 1 of 4 cases (25%) using RP2, and in no single case using the RP3 system (p = 0.03). Most of the observed complications occurred up to 12 months postoperatively. A total plate survival rate of 64.7% and a total plate complication rate of 47.8% were seen. CONCLUSION: In conclusion, it seems that RP3 should be preferred over RP1 and RP2 regarding failure rates and complications.

High-Multiplex Aptamer-Based Serum Proteomics to Identify Candidate Serum Biomarkers of Oral Squamous Cell Carcinoma.

Improved serological biomarkers are needed for the early detection, risk stratification and treatment surveillance of patients with oral squamous cell carcinoma (OSCC). We performed an exploratory study using advanced, highly specific, DNA-aptamer-based serum proteomics (SOMAscan, 1305-plex) to identify distinct proteomic changes in patients with OSCC pre- vs. post-resection and compared to healthy controls. A total of 63 significantly differentially expressed serum proteins (each p < 0.05) were found that could discriminate between OSCC and healthy controls with 100% accuracy. Furthermore, 121 proteins were detected that were significantly altered between pre- and post-resection sera, and 12 OSCC-associated proteins reversed to levels equivalent to healthy controls after resection. Of these, 6 were increased and 6 were decreased relative to healthy controls, highlighting the potential relevance of these proteins as OSCC tumor markers. Pathway analyses revealed potential pathophysiological mechanisms associated with OSCC. Hence, quantitative proteome analysis using SOMAscan technology is promising and may aid in the development of defined serum marker assays to predict tumor occurrence, progression and recurrence in OSCC, and to guide personalized therapies.

GARP Regulates the Immune Capacity of a Human Autologous Platelet Concentrate.

Autologous platelet concentrates, like liquid platelet rich fibrin (iPRF), optimize wound healing; however, the underlying immunological mechanisms are poorly understood. Platelets, the main cellular component of iPRF, highly express the protein, Glycoprotein A repetitions predominant (GARP), on their surfaces. GARP plays a crucial role in maintaining peripheral tolerance, but its influence on the immune capacity of iPRF remains unclear. This study analyzed the interaction of iPRF with immune cells implicated in the wound healing process (human monocyte derived macrophages and CD4+ T cells) and evaluated the distinct influence of GARP on these mechanisms in vitro. GARP was determined to be expressed on the surface of platelets and to exist as a soluble factor in iPRF. Platelets derived from iPRF and iPRF itself induced a regulatory phenotype in CD4+ T cells, shown by increased expression of Foxp3 and GARP as well as decreased production of IL-2 and IFN-γ. Application of an anti-GARP antibody reversed these effects. Additionally, iPRF polarized macrophages to a "M0/M2-like" phenotype in a GARP independent manner. Altogether, this study demonstrated for the first time that the immune capacity of iPRF is mediated in part by GARP and its ability to induce regulatory CD4+ T cells.

Tumor Recurrence and Follow-Up Intervals in Oral Squamous Cell Carcinoma.

Tumor recurrence in oral squamous cell carcinoma (OSCC) is frequent. However, no consensus about follow-up interval is available. The aim of this study was to analyze the recurrence pattern, detection method and associated parameters for possible risk stratification. Histopathological and epidemiological features were obtained retrospectively and correlated with tumor recurrence and overall survival, distant and lymph node metastases. A total of 760 patients were included, of which 216 patients showed tumor recurrence (mean after 24 ± 26 months). Within the first 12 months, 24% of the recurrences were detected. The primary detection method was clinical examination (n = 123, 57%). Tumor recurrence significantly correlated with advanced histopathological grading (G2/3 vs. G1, p < 0.000) and lymph node metastasis (p = 0.004). Tumor recurrence was frequent. Clinical examination was the primary detection method and manifestation within the first 6−12 months was high. The degree of histopathological grading may be useful for risk stratification.

Artemisinin derivative FO-ARS-123 as a novel VEGFR2 inhibitor suppresses angiogenesis, cell migration, and invasion.

Anti-angiogenesis targeting vascular endothelial growth factor receptor 2 (VEGFR2) has been considered an important strategy for cancer therapy. VEGFR2 inhibitors targeting tumor angiogenic pathways have been widely used in clinical cancer treatment. However, inherent or acquired resistance to anti-angiogenic drugs may occur and thus limit their clinical application. New VEGFR2 inhibitors are still highly demanded. The aim of this study was to investigate VEGFR2-targeted artemisinin (ARS)-type compounds for cancer treatment. Here, we reported the ARS derivative FO-ARS-123 as a novel VEGFR2 inhibitor, which displayed potent binding activity with VEGFR2 in in silico by molecular docking (pKi, 0.40 ± 0.31 nM) and in vitro by microscale thermophoresis (Kd, 1.325 ± 0.055 µM). In addition, compound FO-ARS-123 displayed a strong inhibition on cell proliferation of a broad range of cancer cells as well as suppressed cell migration and invasion. Remarkably, FO-ARS-123 exerted profound anti-angiogenesis effects in the in vitro tube formation assay and in vivo CAM assay. These results suggest that FO-ARS-123 might be a novel and promising anti-angiogenesis agent for cancer treatment.

Comparison of Hyperspectral Imaging and Microvascular Doppler for Perfusion Monitoring of Free Flaps in an In Vivo Rodent Model.

To reduce microvascular free flap failure (MFF), monitoring is crucial for the early detection of malperfusion and allows timely salvage. Therefore, the aim of this study was to evaluate hyperspectral imaging (HSI) in comparison to micro-Doppler sonography (MDS) to monitor MFF perfusion in an in vivo rodent model. Bilateral groin flaps were raised on 20 Sprague−Dawley rats. The femoral artery was transected on the trial side and re-anastomosed. Flaps and anastomoses were assessed before, during, and after the period of ischemia every ten minutes for overall 60 min using HSI and MDS. The contralateral sides' flaps served as controls. Tissue-oxygenation saturation (StO2), near-infrared perfusion index (NPI), hemoglobin (THI), and water distribution (TWI) were assessed by HSI, while blood flow was assessed by MDS. HSI correlates with the MDS signal in the case of sufficient and completely interrupted perfusion. HSI was able to validly and reproducibly detect tissue perfusion status using StO2 and NPI. After 40 min, flap perfusion decreased due to the general aggravation of hemodynamic circulatory situation, which resulted in a significant drop of StO2 (p < 0.005) and NPI (p < 0.005), whereas the Doppler signal remained unchanged. In accordance, HSI might be suitable to detect MFF general complications in an early stage and further decrease MFF failure rates, whereas MDS may only be used for direct complications at the anastomose site.

Long-Term Donor Site Morbidity and Flap Perfusion Following Radial versus Ulnar Forearm Free Flap-A Randomized Controlled Prospective Clinical Trial.

This clinical prospective randomized controlled study aimed to investigate the differences between Radial (RFFF) and Ulnar (UFFF) Forearm Free Flap in terms of success, performance, and donor site morbidity. Thirty patients with reconstruction of the head and neck region were included. For the first time, this study assessed flap-perfusion characteristics, donor-site-wound-healing dynamics and hand perfusion using hyperspectral imaging. Further, subjective (Likert-scale, DASH-score) and objective (grip/pinch-strength) parameters of donor site morbidity were analysed. Postoperative follow-up was performed until 6 months after index surgery. With 100% of patients, RFFF and UFFF were equally successful. Compared to surrounding reference, UFFF revealed significant lower tissue oxygenation saturation (StO2) than RFFF. Compared with UFFF, blood flow in both the thenar and hypothenar region were significantly reduced 6 months following RFFF transfer. After four weeks, 27% more patients demonstrated impaired wound healing following RFFF transfer. After 6 months, epithelial-surface continuity was restored in all patients of both groups. After 6 months, overall rates of both subjective and objective donor site morbidity were comparable between RFFF and UFFF. RFFF and UFFF both demonstrate similar success rates and HSI-perfusion dynamics following transfer. After 4 weeks, wound-healing disorder appeared significantly more often in RFFF than in UFFF; however, they became equal after 6 months. RFFF and UFFF can be considered as mutual alternatives.

Novel artemisinin derivative FO8643 with anti-angiogenic activity inhibits growth and migration of cancer cells via VEGFR2 signaling.

The vascular endothelial growth factor receptor 2 (VEGFR2) is widely recognized as a key effector in angiogenesis and cancer progression and has been considered a critical target for the development of anti-cancer drugs. Artemisinin (ARS) and its derivatives exert profound efficacy in treating not only malaria but also cancer. As a novel ARS-type compound, FO8643 caused significant suppression of the growth of a panel of cancer cells, including both solid and hematologic malignancies. In CCRF-CEM leukemia cells, FO8643 dramatically inhibited cell proliferation coupled with increased apoptosis and cell cycle arrest. Additionally, FO8643 restrained cell migration in the 2D wound healing assay as well as in a 3D spheroid model of human hepatocellular carcinoma HUH-7 cells. Importantly, SwissTargetPrediction predicted VEGFR2 as an underlying target for FO8643. Molecular docking simulation further indicated that FO8643 formed hydrogen bonds and hydrophobic interactions within the VEGFR2 kinase domain. Moreover, FO8643 directly inhibited VEGFR2 kinase activity and its downstream action including MAPK and PI3K/Akt signaling pathways in HUH-7 cells. Encouragingly, FO8643 decreased angiogenesis in the chorioallantoic membrane assay in vivo. Collectively, FO8643 is a novel ARS-type compound exerting potential VEGFR2 inhibition. FO8643 may be a viable drug candidate in cancer therapy.

Hyaluronic Acid with Bone Substitutes Enhance Angiogenesis In Vivo.

Introduction: The effective induction of angiogenesis is directly related to the success of bone-substitute materials (BSM) for maxillofacial osseous regeneration. Therefore, the addition of pro-angiogenic properties to a commercially available bovine bone-substitute material in combination with hyaluronic acid (BSM+) was compared to the same bone-substitute material without hyaluronic acid (BSM) in an in-vivo model. Materials and Methods: BSM+ and BSM were incubated for six days on the chorioallantoic membrane (CAM) of fertilized chicken eggs. Microscopically, the number of vessels and branching points, the vessel area and vessel length were evaluated. Subsequently, the total vessel area and brightness integration were assessed after immunohistochemical staining (H&E, alphaSMA). Results: In the BSM+ group, a significantly higher number of vessels (p < 0.001), branching points (p = 0.001), total vessel area (p < 0.001) as well as vessel length (p = 0.001) were found in comparison to the BSM group without hyaluronic acid. Immunohistochemically, a significantly increased total vessel area (p < 0.001 for H&E, p = 0.037 for alphaSMA) and brightness integration (p = 0.047) for BSM+ in comparison to the native material were seen. Conclusions: The combination of a xenogenic bone-substitute material with hyaluronic acid significantly induced angiogenesis in vivo. This might lead to a faster integration and an improved healing in clinical situations.

Differences in PD-L1 Expression between oral and oropharyngeal squamous cell carcinoma.

Treatment of metastasized or recurrent oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinoma remains challenging. Targeted antibody-based therapy inter alia for PD-1 / PD-L1 axis shows promising results, but whether PD-L1 expression varies between the subentities remains unclear. The expression pattern of PD-L1 (EPR19759 antibody, Abcam, Berlin, Germany) and p16 (CINtech® Histology Kit, Ventana, Oro Valley, USA) was determined immunohistochemically and analyzed by HALO™ Image Analysis Software (Indica Lab, Albuquerque, USA). For PD-L1, combined positivity score (CPS), tumor proportion score (TPS) and histoscore, were assessed and results correlated with epidemiological data. In total, 161 patients (OSCC: n = 78, OPSCC: n = 83) were included. A mean of 43.6% (±34.0%) of the specimen showed increased PD-L1 expression that did not differ quantitatively between subentities (TPS: p = 0.159, CPS: p = 0.078), but qualitatively (histoscore: p = 0.003). In the mean follow-up period (45.6 months), contrary to age (p = 0.006) and advanced T-Status (p = 0.018), PD-L1 expression did not correlate with overall (OS, p = 0.191) and recurrence free survival (RFS: p = 0.193) in both subentities. No correlation of p16 and PD-L1 expression was found (p = 0.844). PD-L1 is differentially expressed between OSCC and OPSCC, however without influence on OS. Furthermore, p16 status was not related to PD-L1 expression. This may have implications for future (immune) therapeutical approaches for oral cancer.

Biofunctionalization of Xenogeneic Collagen Membranes with Autologous Platelet Concentrate-Influence on Rehydration Protocol and Angiogenesis.

Background: The aim of this study was to analyze possible interactions of different xenogeneic collagen membranes (CM) and platelet-rich fibrin (PRF). PH values were evaluated in the CM rehydration process with PRF, and their influence on angiogenesis was analyzed in vivo. Materials and Methods: Porcine (Bio-Gide®, Geistlich)- and bovine-derived collagen membranes (Symbios®, Dentsply Sirona) were biofunctionalized with PRF by plotting process. PRF in comparison to blood, saline and a puffer pH7 solution was analysed for pH-value changes in CM rehydration process in vitro. The yolk sac membrane (YSM) model was used to investigate pro-angiogenic effects of the combination of PRF and the respective CM in comparison to native pendant by vessel in-growth and branching points after 24, 48 and 72 h evaluated light-microscopically and by immunohistochemical staining (CD105, αSMA) in vivo. Results: Significantly higher pH values were found at all points in time in PRF alone and its combined variants with Bio-Gide® and Symbios® compared with pure native saline solution and pH 7 solution, as well as saline with Symbios® and Bio-Gide® (each p < 0.01). In the YSM, vessel number and branching points showed no significant differences at 24 and 48 h between all groups (each p > 0.05). For PRF alone, a significantly increased vessel number and branching points between 24 and 48 h (each p < 0.05) and between 24 and 72 h (each p < 0.05) was shown. After 72 h, CM in combination with PRF induced a statistically significant addition to vessels and branching points in comparison with native YSM (p < 0.01) but not vs. its native pendants (p > 0.05). Summary: PRF represents a promising alternative for CM rehydration to enhance CM vascularization.

Biomechanical Characterization of a New Acellular Dermal Matrix for Oral Soft Tissue Regeneration.

OBJECTIVES: Acellular dermal matrices (ADM) are a suitable alternative to autogenous soft tissue grafts (ASG). The aim of this study was to analyze the biomechanical properties and architectural features of ASG and ADM. MATERIALS AND METHODS: ASG were harvested from the hard palate of fresh frozen body donors as connective tissue grafts and compared to ADM of porcine origin (NovoMatrix, NM; mucoderm, MD). Maximum load (ML, Newton [N]) and expansion (E, [mm]) were measured after rehydration in saline solution by tensile strength measurement. Light microscopy (LM) and scanning electron microscopy (SEM) were performed to analyze the architectural features of ASG and ADM in high resolution. RESULTS: ASG demonstrated a significantly decreased ML compared to NM and MD (p < 0.0001 and p = 0.019). NM showed a significantly increased ML compared to MD (p = 0.001). ASG demonstrated a non-significantly reduced E compared to NM (p = 0.13) and a significantly increased E compared to MD (p = 0.025). NM showed an increased E compared to MD (p < 0.0001). LM and SEM highlighted the surface characteristics and internal structures of ASG and ADM, such as the surface compact layer of MD and the densely packed, parallel running and ordered collagen fibers of NM and MD. CONCLUSIONS: Significant differences concerning the biomechanical properties and architectural features of ASG, and ADM were found. CLINICAL RELEVANCE: Information about the biomechanical properties and architectural features of ASG and ADM can contribute to a better understanding of the clinical performance and extend the application area.

Non-Interventional Prospective Observational Study of Platelet Rich Fibrin as a Therapy Adjunctive in Patients with Medication-Related Osteonecrosis of the Jaw.

BACKGROUND: Medication-related osteonecrosis (MRONJ) of the jaw is a severe and feared side effect of antiresorptive therapy in the oncological setting. With growing evidence that impaired angiogenesis may represent a key factor in pathogenesis, the aim of this study was to evaluate an autologous platelet concentrate as a possible additive in surgical therapy to optimize vascularization and, subsequently, resolution rates. MATERIAL AND METHODS: A non-interventional, prospective, multicenter study was conducted, and all patients with stage I-III MRONJ, undergoing antiresorptive therapy for an oncological indication, were included. The necrosis was treated surgically without (study arm A) or with (arm B) the addition of an autologous platelet concentrate (platelet-rich fibrin, PRF). RESULTS: After 5, 14, and 42 days postoperative, wound healing (primary outcome: mucosal integrity) as well as downstaging, pain perception, and oral health-related quality of life (secondary outcome) were assessed via clinical evaluation. Among the 52 patients included, primarily with MRONJ stage I and II, the use of PRF as an additive in surgical therapy did not display a significant advantage for wound healing (p = 0.302), downstaging (p = 0.9), pain reduction (p = 0.169), or quality of life (p = 0.9). SUMMARY: In conclusion, PRF as an adjunct did not significantly optimize wound healing. Further, no significant changes in terms of downstaging, pain sensation, and oral health-related quality of life were found.

Oral Squamous Cell Carcinomas Developing from Oral Lichen Planus: A 5-21 year Retrospective Study.

Background and Aims: There is insufficient data regarding clinical characteristics, relapse rates, as well as lymph node metastasis of squamous cell carcinomas of the oral cavity (OSCC) developing from oral lichen planus (OLP-OSCC). The aim of this retrospective study was to evaluate clinical characteristics, as well as relapse, recurrence and survival rates of OLP-OSCC. Methods: In a retrospective monocenter analysis, all consecutive patients with an OSCC treated in the time period 1st January 2000-December 31 2016 were reviewed. All patients with OSCC developing from OLP/OLL (oral lichenoid lesions) were identified and analyzed for epidemiological data, risk profile, location of primary tumor, pTNM classification, lymph node metastasis, primary therapy, recurrence, and outcome. Results: A total of 103 patients (45%♂/ 55%♀) with an average age of 62 ± 14 year were included in this study. At the time of initial diagnosis, 17% (n = 18) of patients had cervical metastases (CM) whereas only 11% (11 patients) displayed advanced tumor sizes (T > 2). T-status (p = 0.003) and histopathological grading (p = 0.001) had an impact on the incidence of CM. 39.6% of the patients developed a relapse after an average of 24 months with a mean of two recurrences per patient. Advanced tumor size had a significant impact on the 5 year overall survival and was associated with disease-free survival of the patients (p < 0.001, respectively p = 0.004). Conclusion: Although initial lymph node metastases were not more frequent, more aggressive recurrence patterns compared to OSCC were seen for OLP-OSCC. Therefore, based on the study results, a modified recall for these patients is suggested.

New Approach to the Old Challenge of Free Flap Monitoring-Hyperspectral Imaging Outperforms Clinical Assessment by Earlier Detection of Perfusion Failure.

In reconstructive surgery, free flap failure, especially in complex osteocutaneous reconstructions, represents a significant clinical burden. Therefore, the aim of the presented study was to assess hyperspectral imaging (HSI) for monitoring of free flaps compared to clinical monitoring. In a prospective, non-randomized clinical study, patients with free flap reconstruction of the oro-maxillofacial-complex were included. Monitoring was assessed clinically and by using hyperspectral imaging (TIVITA™ Tissue-System, DiaspectiveVision GmbH, Pepelow, Germany) to determine tissue-oxygen-saturation [StO2], near-infrared-perfusion-index [NPI], distribution of haemoglobin [THI] and water [TWI], and variance to an adjacent reference area (Δreference). A total of 54 primary and 11 secondary reconstructions were performed including fasciocutaneous and osteocutaneous flaps. Re-exploration was performed in 19 cases. A total of seven complete flap failures occurred, resulting in a 63% salvage rate. Mean time from flap inset to decision making for re-exploration based on clinical assessment was 23.1 ± 21.9 vs. 18.2 ± 19.4 h by the appearance of hyperspectral criteria indicating impaired perfusion (StO2 ≤ 32% OR StO2Δreference > -38% OR NPI ≤ 32.9 OR NPIΔreference ≥ -13.4%) resulting in a difference of 4.8 ± 5 h (p < 0.001). HSI seems able to detect perfusion compromise significantly earlier than clinical monitoring. These findings provide an interpretation aid for clinicians to simplify postoperative flap monitoring.