Immunomodulation of Cancer Cells Using Autologous Blood Concentrates as a Patient-Specific Cell Culture System: A Comparative Study on Osteosarcoma and Fibrosarcoma Cell Lines.

The understanding that tumor cells might evade immunity through various mutations and the potential of an augmented immune system to eliminate abnormal cells led to the idea of utilizing platelet-rich fibrin (PRF), a blood concentrate containing the body's immune elements as an adjunctive therapy for localized tumors. This study is the first that evaluated the effect of PRF generated with different relative centrifugal forces (RCFs) on osteoblastic and fibroblastic tumor cell lines MG63 and HT1080 with regard to cell viability, cytokine and growth factor release, and the gene expression of factors related to the cell cycle and apoptosis. Our findings could demonstrate decreased cell proliferation of MG63 and HT1080 when treated indirectly with PRF compared to cell cultures without PRF. This effect was more distinct when the cells were treated with low-RCF PRF, where higher concentrations of growth factors and cytokines with reduced RCFs can be found. Similar patterns were observed when assessing the regulation of gene expression related to the cell cycle and apoptosis in both MG63 and HT1080 cells treated with PRF. Despite variations, there was a consistent trend of an up-regulation of tumor-suppressive genes and a down-regulation of anti-apoptotic genes in both cell types following treatment with high- and, particularly, low-RCF PRF formulations.

Leukocytes within Autologous Blood Concentrates Have No Impact on the Growth and Proliferation of Human Primary Osteoblasts: An In Vitro Study.

Platelet-rich fibrin (PRF) is a widely used autologous blood concentrate in regenerative medicine. This study aimed to characterize the cellular composition and distribution of different PRF matrices generated by high (710 g) and low (44 g) relative centrifugal forces (RCFs) and to analyze their bioactivity on human primary osteoblasts (pOBs). PRF was separated into upper layer (UL) and buffy coat (BC) fractions, and their cellular contents were assessed using histological and immunohistochemical staining. The release of platelet-derived growth factor (PDGF) and transforming growth factor (TGF-ß) was quantified using an ELISA. Indirect PRF treatment on pOBs was performed to evaluate cell viability and morphology. A histological analysis revealed higher quantities of leukocytes and platelets in the low-RCF PRF. TGF-ß release was significantly higher in the low-RCF PRF compared to the high-RCF PRF. All PRF fractions promoted pOB proliferation regardless of the centrifugation protocol used. The low-RCF PRF showed higher TGF-ß levels than the high-RCF PRF. These findings contribute to understanding the cellular mechanisms of PRF and provide insights into optimizing PRF protocols for bone regeneration, advancing regenerative medicine, and improving patient outcomes.

Histologic evaluation of edentulous alveolar ridge horizontal bone augmentations using a xenogeneic bone substitute and autologous platelet concentrates: a case series.

OBJECTIVES: This case series aimed to assess the efficacy of a novel horizontal ridge augmentation modality using histology. Combinations of "sticky bone" and tenting screws without autologous bone were used as augmentative materials. METHOD AND MATERIALS: Five individuals presenting healed, atrophic, partially edentulous sites that required horizontal bone augmentation before implant placement were enrolled. Patients underwent the same augmentation type and 5 months of postoperative reentry procedures. The first surgery served as implant site development, whereas the biopsy and corresponding implant placement were performed during reentry. The bone was qualitatively analyzed using histology and histomorphometry and quantitatively evaluated using CBCT. RESULTS: Four individuals healed uneventfully. Early wound dehiscence occurred in one case. Histology showed favorable bone substitute incorporation into the newly formed bone and intimate contact between de novo bone and graft material in most cases. Histomorphometry revealed an average of 48 ± 28% newly formed bone, 19 ± 13% graft material, and 33 ± 26% soft tissue components. The CBCT-based mean alveolar ridge horizontal increase was 3.9 ± 0.6 mm at 5 months postoperatively. CONCLUSIONS: The described augmentation method appears suitable for implant site development resulting in favorable bone quality according to histology. However, clinicians must accommodate 1 to 2 mm of resorption in augmentative material width at the buccal aspect.

Three Milliliters of Peripheral Blood Is Sufficient for Preparing Liquid Platelet-Rich Fibrin (PRF): An In Vitro Study.

Platelet-rich fibrin (PRF) has assumed an important role in supporting tissue regeneration in different fields. To date, the standard protocol for liquid PRF requires at least 10 mL of peripheral blood. The present study aimed to analyze the composition, growth factor release, and effects on the cell proliferation of PRF samples produced using 3 mL vs. 10 mL of peripheral blood in vitro. Peripheral venous blood from six healthy donors was used to prepare liquid PRF using either 3 mL or 10 mL tubes. Three different centrifugation protocols were used according to the low-speed centrifugation concept. The cellular distribution was evaluated using immunohistology and automated cell count. ELISA was used to determine the release of different growth factors (EGF, TGF-ß1, and PDGF) and interleukin 8 at different time points. Primary human osteoblasts (pOBs) were cultivated for 7 days using PRF-conditioned media acquired from either 3 mL or 10 mL of peripheral blood. The results showed that 3 mL of peripheral blood is sufficient to produce a liquid PRF concentrate similar to that acquired when using 10 mL blood. The concentrations of platelets and leukocytes were comparable regardless of the initial blood volume (3 mL vs. 10 mL). Similarly, the release of growth factors (EGF, TGF-ß1, and PDGF) and interleukin 8 was often comparable in both groups over 7 days. The cultivation of pOBs using PRF-conditioned media showed a similar proliferation rate regardless of the initial blood volume. This proliferation rate was also similar to that of pOBs treated with 20% FBS-conditioned media. These findings validated the use of 3 mL of peripheral blood to generate liquid PRF matrices according to the low-speed centrifugation concept, which may open new application fields for research purposes such as in vivo experiments and clinical applications such as pediatric surgery.

Platelet rich fibrin as a bioactive matrix with proosteogenic and proangiogenic properties on human healthy primary cells in vitro.

Blood concentrates like platelet rich fibrin (PRF) have been established as a potential autologous source of cells and growth factors with regenerative properties in the field of dentistry and regenerative medicine. To further analyze the effect of PRF on bone tissue regeneration, this study investigated the influence of liquid PRF matrices on human healthy primary osteoblasts (pOB) and co-cultures composed of pOB and human dermal vascular endothelial cells (HDMEC) as in vitro model for bone tissue regeneration. Special attention was paid to the PRF mediated influence on osteoblastic differentiation and angiogenesis. Based on the low-speed centrifugation concept, cells were treated indirectly with PRF prepared with a low (44 g) and high relative centrifugal force (710 g) before the PRF mediated effect on osteoblast proliferation and differentiation was assessed via gene and protein expression analyses and immunofluorescence. The results revealed a PRF-mediated positive effect on osteogenic proliferation and differentiation accompanied by increased concentration of osteogenic growth factors and upregulated expression of osteogenic differentiation factors. Furthermore, it could be shown that PRF treatment resulted in an increased formation of angiogenic structures in a bone tissue mimic co-culture of endothelial cells and osteoblasts induced by the PRF mediated increased release of proangiogenic growth factors. The effects on osteogenic proliferation, differentiation and vascularization were more evident when low RCF PRF was applied to the cells. In conclusion, PRF possess proosteogenic, potentially osteoconductive as well as proangiogenic properties, making it a beneficial tool for bone tissue regeneration.

What is the context?The treatment of bone defects is still a challenge in the field of regenerative medicine. In this context, researchers and clinicians are continuously focusing on developing new therapeutic strategies like the use of autologous blood concentrates like Platelet rich fibrin (PRF) to improve regeneration by directly delivering wound healing promoting cells and growth factors to the defect side in order to restore the structure and functional integrity of damaged hard tissue in combination with adequate tissue regeneration.What is new?Focus of the present in vitro study was to further evaluate the potential of PRF paying particular attention to the PRF-mediated effect on osteogenic differentiation and angiogenesis of human primary osteoblasts as well as on a more complex tissue like co-culture consisting of osteoblasts and microvascular endothelial cells. We could demonstrate that PRF is able to support and affect a variety of processes involved in bone tissue regeneration including osteogenic proliferation, osteogenic differentiation as well as angiogenic structure formation.Treatment of PRF resulted in:- increased cell viability*- higher expression of osteogenic differentiation factors*- higher release of osteogenic growth factors*- increased formation of microvessel-like structures*(*compared to untreated control)What is the impact?PRF represents a beneficial autologous tool for regenerative purposes combining proosteogenic and proangiogenic properties. Therefore, PRF might be used for applications in versatile fields of medicine in the context of improving bone tissue regeneration.

Long-Term Peri-Implant Health and Papilla Formation at Healed Sites by Chairside Provisionalization of Single-Tooth Implants: A Prospective Case Series.

PURPOSE: Several procedures are performed to achieve optimal esthetic results in single-tooth implants. However, there is discordance regarding the potential benefit and risks of immediate implant loading/provisionalization. The aim of this prospective case series is to investigate the effect of immediate provisionalization of single-tooth implants at healed sites for periimplant soft-tissue conditions, focusing on papilla formation around single implants. MATERIALS AND METHODS: Twelve patients received a total of 12 implants in the incisor, canine or premolar region of the upper and lower jaw at healed sites with immediate chair-side provisionalization. Four months later, the temporary crown was replaced by the permanent crown. After 40±13.1 months, clinical follow-up was conducted, assessing Probing pocket depth (PPD); Bleeding on Probing(BoP); Mucosal recession (MR) and Width of Keratinized Mucosa (KM). Papilla index (PI) was determined immediately after implant placement (baseline), before removing the temporary crown (t1), 4 weeks after insertion of the definitive crown (t2) and at the final follow-up examination (t3) to evaluate papilla formation and its change over time. RESULTS: None of the implants were lost. The mean PPD was 2.5±0.39 mm, BoP of 25% and 3.5 mm of KM were observed at the final follow-up. No implants showed MR. PI increased in all patients from 1.5±0.45 at baseline to 2.4±0.56 at t1, 2.6±0.47 at t2 and 3.02.6±0 at t3. The increase in PI between t0 and each individual timepoint from t1-t3 showed statistical significance. CONCLUSION: The present results indicate the suitability and benefit of immediate provisionalization to achieve favorable peri-implant soft-tissue conditions and papilla formation.

From the Oral Cavity to the Spine: Prevalence of Oral Cavity Infections in Patients with Pyogenic Spinal Infection.

Background incidence of pyogenic spinal infections has increased in recent years. In addition to treating the spinal infection, optimal care also includes identifying the source of the pyogenic spinal infection and the presence of other infections. The aim of this study is to elucidate the prevalence of oral cavity infection (OCI) within this patient cohort. Methods As part of a prospective study conducted from 2016 to 2021, the number of patients with dental infections was investigated by means of an orthopantomogram (OPG) and subsequent dental examination. Results The presence of an oral infection was investigated in 55 (47%) of 118 patients by an OPG, 29 (53%) of whom had a corresponding abnormality of the oral cavity. In addition to the spinal infection, patients with an oral cavity infection revealed an increased incidence of endocarditis, sepsis and brain abscess. A spinal epidural abscess, a multilevel affection of the infection, and an elevated CRP value were also found in patients with a co-existing oral cavity infection. Back pain assessed at admission and 3 months after surgery was also more pronounced in patients with an oral cavity infection. Neurological deficits were often present in patients with spinal and oral cavity infection. Conclusions The presence of an oral cavity infection has proven to be one of the important factors in the detection of the source of the pyogenic spinal infection. In addition, a pronounced spinal affection and frequent co-infections were seen in patients with an oral cavity infection.

Effectiveness of Oroantral Communication Closure Using Solid Platelet-Rich Fibrin Compared to a Conventional Treatment Approach: A Randomized Clinical Trial.

This study aimed to compare the effectiveness of platelet-rich fibrin clot (PRF) and conventional oroantral communication (OAC) repair techniques following tooth extractions from the maxilla. The study involved 22 patients, divided into 2 groups: a study group treated with PRF and a control group undergoing conventional OAC repair. The primary outcome measured was the effectiveness of OAC closure, with pain intensity and postoperative complications as secondary outcomes. Cone-beam computed tomography (CBCT) was used to evaluate post-extraction bone regeneration. Pain was assessed using the Visual Analogue Scale (VAS) on days 0, 1, 7, and 14 postoperatively. The results showed that the PRF group experienced a significant decrease in pain within the first 24 hours and after 7 days (P < .0001; P < .05). In contrast, complications were reported in 45.45% of patients in the conventional repair group and 18.18% in the A-PRF group. Three months postsurgery, CBCT revealed appreciable bone healing in both groups, with no significant difference (P > .05). In conclusion, the study suggests that A-PRF treatment for OACs resulted in fewer complications and quicker pain reduction than traditional repair methods, making it a promising alternative for managing OACs. However, future studies are needed to confirm these findings and establish the full therapeutic potential of PRF.

Fucoidan/chitosan hydrogels as carrier for sustained delivery of platelet-rich fibrin containing bioactive molecules.

Platelet-rich fibrin (PRF), derived from human blood, rich in wound healing components, has drawbacks in direct injections, such as rapid matrix degradation and growth factor release. Marine polysaccharides, mimicking the human extracellular matrix, show promising potential in tissue engineering. In this study, we impregnated the self-assembled fucoidan/chitosan (FU_CS) hydrogels with PRF obtaining PRF/FU_CS hydrogels. Our objective was to analyze the properties of a hydrogel and the sustained release of growth factors from the hydrogel that incorporates PRF. The results of SEM and BET-BJH demonstrated the relatively porous nature of the FU_CS hydrogels. ELISA data showed that combining FU_CS hydrogel with PRF led to a gradual 7-day sustained release of growth factors (VEGF, EGF, IL-8, PDGF-BB, TGF-ß1), compared to pure PRF. Histology confirmed ELISA data, demonstrating uniform PRF fibrin network distribution within the FU_CS hydrogel matrix. Furthermore, the FU_CS hydrogels revealed excellent cell viability. The results revealed that the PRF/FU_CS hydrogel has the potential to promote wound healing and tissue regeneration. This would be the first step in the search for improved growth factor release.

Current Knowledge on the Healing of the Extraction Socket: A Narrative Review.

The concept of extraction socket healing has been severally researched and reported over the years, since tooth extraction remains one of the most common procedures performed in the dental clinic. Understanding this healing process is of utmost importance because the outcome has a direct bearing on future prosthetic rehabilitation and, by extension, on patients' esthetics and masticatory function, among others. This mini review, therefore, summarized the current knowledge on the different stages of socket healing, including the biologic and clinical events that occur following tooth extraction up until the complete closure of the socket. Additionally, the modeling of the alveolar bone/process post extraction, and the resultant dimensional changes that, altogether, shape the bone, were reviewed and documented. The effects of various socket preservation interventions to mitigate these dimensional changes, and therefore preserve the alveolar process in a condition suitable for future prosthetic rehabilitation, were highlighted. Finally, a review of some of the factors that influence the entire process was also carried out.

Platelet-Rich Fibrin-Conditioned Medium as an Alternative to Fetal Bovine Serum Promotes Osteogenesis of Human Dental Pulp Stem Cells.

Human dental pulp stem cells (DPSCs) exhibit multilineage differentiation capabilities and superior clonogenic and proliferative properties. However, the use of animal-derived components such as FBS raises concerns regarding the clinical application of stem-cell-based therapies. Platelet-rich fibrin (PRF) derived from human blood is rich in fibrin, platelets, and growth factors and acts as a bioactive scaffold for grafting with biomaterials. In this study, we assessed the efficacy of PRF-conditioned medium (CM) in promoting DPSCs proliferation and osteogenic differentiation compared with the standard culture medium supplemented with FBS. A comparison of DPSCs cultured in FBS and PRF-CM revealed no differences in characteristics or morphology. However, cells cultured with PRF-CM exhibited inferior proliferation rates and cell numbers during passage in comparison with those cultured with FBS. In contrast, DPSCs cultured in PRF-CM showed significantly higher levels of calcification, and RT-PCR confirmed that the gene expression levels of markers associated with osteoblast differentiation were significantly increased. The PRF-CM approach offers a convenient, straightforward, and advantageous method for culturing DPSCs, without relying on animal-derived components. In summary, this study introduces a novel application of PRF-CM for enhancing the osteogenesis of DPSCs, which provides an alternative to FBS culture medium and addresses concerns associated with the use of animal-derived components in clinical settings.

Standardization of Animal Models and Techniques for Platelet-Rich Fibrin Production: A Narrative Review and Guideline.

Experimental research is critical for advancing medical knowledge and enhancing patient outcomes, including in vitro and in vivo preclinical assessments. Platelet-rich fibrin (PRF) is a blood by-product that has garnered attention in the medical and dental fields due to its potential for tissue regeneration and wound healing. Animal models, such as rabbits and rats, have been used to produce PRF and examine its properties and applications. PRF has demonstrated potential in the dental and medical fields for reducing inflammation, promoting tissue repair, and accelerating wound healing. This narrative review aims to compare existing evidence and provide guidelines for PRF animal research, emphasizing the importance of standardizing animal models, following ethical considerations, and maintaining transparency and accountability. The authors highlight the necessity to use the correct relative centrifugal force (RCF), standardize centrifugal calibration, and report detailed information about blood collection and centrifuge parameters for reproducible results. Standardizing animal models and techniques is crucial for narrowing the gap between laboratory research and clinical applications, ultimately enhancing the translation of findings from bench to bedside.

Adjuvant Radiotherapy in Patients with Squamous Cell Carcinoma of the Oral Cavity or Oropharynx and Solitary Ipsilateral Lymph Node Metastasis (pN1)-A Prospective Multicentric Cohort Study.

(1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55-1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15-0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19-0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group.

The role of magnetic resonance imaging and computed tomography in oral squamous cell carcinoma patients' preoperative staging.

Introduction: The aim of the study was to evaluate the accuracy of MRI and CT with regard to the detection of lymph node metastases based on the data of specific patients with OSCC who received bilateral neck dissection. Materials and methods: In a retrospective analysis from 01/2014 to 12/2020 patients who underwent primary tumor resection and bilateral neck dissection were evaluated. Results: 174 preoperative MRI (78.74%, N=137) and CT (21.26%, N=37) were correlated with the histopathological findings. CT had a sensitivity of 67% and specificity of 68% (p=0.76). MRI showed an overall sensitivity of 66% and a specificity of 68% (p=0.76). In 52.87% of all cases no differences between cN and pN were found. MRI is the method to overestimate lymph node involvement compared to CT (overestimation in 27% vs. 21.62%). Conclusion: The current data indicate that MR and CT show poor efficacy in the detection of cervical metastases. Accordingly, attention must be paid to alternatives to correct local staging modalities. The application of structured bilateral neck dissection needs to be questioned.

Combination of Advanced Platelet-Rich Fibrin and Pentoxifylline/Tocopherol as a Novel Preventive Option in Osteoradionecrosis: A Case Report.

Osteoradionecrosis (ORN) of the jaws is an uncommon complication of radiation therapy that seriously affects the oral and maxillofacial region. Management of ORN is intrinsically difficult and treatment effects are unpredictable. ORN can be treated with pentoxifylline/tocopherol and autologous platelet concentrates to promote wound healing. Furthermore, the low speed of relative centrifugal forces platelet-rich fibrin (PRF + ) has been shown high efficacy for ORN. A 72-year-old male patient with history of radiation treatment for squamous cell carcinoma in the left side of the tongue. Six years after the treatment, his upper right first molar tooth (no. 16) was surgically extracted due to persistent pain. A few months following the extraction, intraoral examination showed gingival inflammation, and pain when palpation around the edentulous area of tooth no. 16. Radiological examination revealed retained root of 16 with radiolucent area and horizontal bone loss around upper right second molar tooth (no. 17). Pentoxifylline and tocopherol were given for a week before the surgical operation and were continued for 8 weeks after the operation. Retained roots of teeth no. 16 and 17 were removed and the sockets were debrided, the advanced PRF+ (A-PRF + ) membranes were placed followed by primary wound closure. Following 2 weeks of treatment, the mucosa healed and progressed to complete mucosal coverage at 2 months with no pathological findings or ORN progression. At 6-month follow-up, clinical and cone-beam computed tomography (CBCT) revealed no pathology. Our case demonstrates that the combination of pentoxifylline/tocopherol and the A-PRF+ surgical approach can be useful for wound healing and prevention of ORN.

Hyperspectral Imaging Allows Evaluation of Free Flaps in Craniomaxillofacial Reconstruction.

INTRODUCTION: Treatment of extended defects after tumor resection in oral, maxillofacial, and facial surgery (craniomaxillofacial) is usually performed by free microvascular flaps. Evaluation of flap survival is crucial, especially in the first hours after insertion and connection. For flap evaluation various invasive and noninvasive methods have been developed. This retrospective clinical study examined the ability of a hyperspectral imaging (HSI) camera (Tivita, Diaspective Vision, Germany) to assess postoperative flap properties in comparison to established clinical parameters. MATERIALS AND METHODS: Thirteen patients with tumor resection and free flap reconstruction were included for camera analysis and another 10 patients as control group. For this purpose, at defined time intervals and under standardized conditions, recordings of transplants 3 to 100 hours postoperatively were performed. Images were used to examine oxygenation (StO 2 %), tissue hemoglobin index, tissue water index, near infrared range perfusion index of free flaps quantitatively and qualitatively. RESULTS: HSI provides values differing between patients observed with no intraindividual significant difference. After 24 hours a mean reduction of 16.77% for StO 2 %, 9.16% for tissue hemoglobin index and 8.46% was observed, going in line with no loss of flap was noted in the observation period. CONCLUSION: HSI is suitable as a noninvasive measure for the evaluation of free flaps in craniomaxillofacial surgery in case of stable imaging conditions with respect to light, surrounding and position of the camera. However, clinical measurements are still the method of choice.

Interaction of Telomere Length and Inflammatory Biomarkers Following Zirconia Implant Placement: A Case Series.

Zirconia implants have gained popularity for their aesthetic appeal and biocompatibility, making them a preferred choice for anterior teeth replacement. This study explores the interaction between telomere length and inflammatory biomarkers in seven cases of zirconia implant placement to gain insights into postoperative cellular aging, inflammatory responses, and long-term outcomes. Zirconia implants offer advantages over titanium implants, as they do not corrode or release metal ions, leading to potential inflammation and implant failure. Monitoring immune and inflammatory biomarkers is essential to assess inflammation initiation, severity, and progression. C-reactive protein (CRP) and pro-inflammatory cytokines, like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), play crucial roles in host immune responses, while anti-inflammatory cytokines, including interleukin-10 (IL-10), regulate and dampen immune responses. Achieving a delicate balance between pro- and anti-inflammatory cytokines is vital for maintaining a healthy immune response and preventing chronic inflammatory conditions. Telomeres, protective structures present at chromosome ends, influence cellular aging and mitochondrial function. Shorter telomeres are associated with impaired mitochondrial function, increased oxidative stress, and cellular senescence, while longer telomeres are linked to reduced inflammation and improved immune function. Understanding these mechanisms is essential for addressing age-related conditions and promoting overall well-being. In this case series, we investigated the interaction between telomere length and inflammatory biomarkers in patients who received zirconia dental implants. The study aims to improve our understanding of postoperative cellular aging, inflammatory responses, and the biocompatibility of zirconia implants, potentially leading to improved treatment protocols and patient outcomes. This innovative assessment of telomere length and inflammatory biomarkers in the context of zirconia implants provides novel insights into the field of dental implantology. By exploring the effects of zirconia implants on cellular health and inflammation, this study contributes to advancements in implant technology and patient care.

DAR 16-II Primes Endothelial Cells for Angiogenesis Improving Bone Ingrowth in 3D-Printed BCP Scaffolds and Regeneration of Critically Sized Bone Defects.

Bone is a highly vascularized tissue and relies on the angiogenesis and response of cells in the immediate environmental niche at the defect site for regeneration. Hence, the ability to control angiogenesis and cellular responses during osteogenesis has important implications in tissue-engineered strategies. Self-assembling ionic-complementary peptides have received much interest as they mimic the natural extracellular matrix. Three-dimensional (3D)-printed biphasic calcium phosphate (BCP) scaffolds coated with self-assembling DAR 16-II peptide provide a support template with the ability to recruit and enhance the adhesion of cells. In vitro studies demonstrated prompt the adhesion of both human umbilical vein endothelial cells (HUVEC) and human mesenchymal stem cells (hMSC), favoring endothelial cell activation toward an angiogenic phenotype. The SEM-EDS and protein micro bicinchoninic acid (BCA) assays demonstrated the efficacy of the coating. Whole proteomic analysis of DAR 16-II-treated HUVECs demonstrated the upregulation of proteins involved in cell adhesion (HABP2), migration (AMOTL1), cytoskeletal re-arrangement (SHC1, TMOD2), immuno-modulation (AMBP, MIF), and morphogenesis (COL4A1). In vivo studies using DAR-16-II-coated scaffolds provided an architectural template, promoting cell colonization, osteogenesis, and angiogenesis. In conclusion, DAR 16-II acts as a proactive angiogenic factor when adsorbed onto BCP scaffolds and provides a simple and effective functionalization step to facilitate the translation of tailored 3D-printed BCP scaffolds for clinical applications.