Search Results (9)

Knee osteoarthritis is commonly managed with intra-articular therapies that differ widely in composition, mechanism, and clinical persistence, yet the duration of their benefit is discussed inconsistently, which limits practical comparison between ozone, hyaluronic acid, platelet-derived products, and cell-rich orthobiologics. In this narrative review we examine the mechanism-driven temporal behavior of these therapies, focusing on the physicochemical, biomechanical, biological, and regenerative factors that influence how long a clinical response persists. By temporal hierarchy we mean the mechanistically informed pattern by which therapies differ in the duration of their physicochemical presence, biological activity, and clinical benefit, not a ranking of efficacy or a claim of equivalence. Read against this definition, ozone occupies the shortest end of the spectrum; conventional hyaluronic acid shows intermediate persistence; modified hyaluronic acid hydrogels may extend activity through improved rheology and enzymatic resistance; platelet-rich plasma and injectable platelet-rich fibrin provide more sustained biological signaling; and bone marrow aspirate concentrate and stromal vascular fraction may act over longer periods through trophic and paracrine pathways. Heterogeneity in study design, patient selection, and outcome reporting still limits firm conclusions, and standardized reporting of product characteristics and time-related endpoints will be essential to validate or refine the proposed framework. Full article

Background: Extended platelet-rich fibrin (e-PRF) membranes are a novel 100% autologous biomaterial with a longer resorption time (4–6 months) than traditional solid-PRF membranes (two weeks). In part 1 of this 2-part publication series, four clinical variations for using these novel e-PRF membranes for socket preservation were introduced. In this randomized clinical trial (RCT), all four iterations of e-PRF membranes were compared to traditional collagen membranes in alveolar ridge preservation for hard and soft tissue dimensional changes and early wound healing outcomes. Methods: A single-center RCT was conducted, including 55 patients requiring the extraction of a single tooth with planned implant placement. All sockets were grafted with a “sticky bone” (bone allograft mixed with PRF) and secured with either a collagen membrane (control) or e-PRF membranes utilizing the four variations present in Part 1 (both formed extra-orally or intra-orally, each with or without an overlying solid PRF membrane). The time of fabrication and application of each e-PRF iteration was recorded. Cone beam computed tomography was utilized to evaluate horizontal and vertical ridge dimensions at baseline and 3 months post-operatively, and soft tissue thickness was also measured at both time intervals utilizing an endodontic reamer. Early wound healing was recorded at 2 weeks, utilizing the Landry, Turnbull, and Howley Index by three blinded clinicians. Results: The results demonstrated that, at 3 months, the e-PRF membranes fabricated utilizing all 4 treatment variations demonstrated equal improvements in horizontal and vertical ridge dimensions and soft tissue thickness when compared to collagen membranes. Additionally, the membrane (p = 0.029) and membrane w/solid (p = 0.021) groups demonstrated statistically significant superior early wound healing compared to the collagen membrane group. Notably, the Bio-Filler groups demonstrated statistically significant reduction in fabrication/application time compared to the membrane groups. Conclusions: Within the limitations of this RCT, all e-PRF iterations performed comparably to collagen membranes in maintaining both hard and soft tissue ridge dimensions when combined with sticky bone, while also significantly improving soft tissue wound healing. Future RCTs with alternative grafting materials, direct wound-margin assessment, and evaluation of patient-reported outcomes are necessary to clarify the advantages of each membrane type. Full article

Background: Platelet-rich fibrin (PRF) is an autologous biomaterial utilized as an adjunct in dental implant surgeries owing to its significant biocompatibility, supra-physiological concentration of growth factors, and ability to speed either soft or hard tissue regeneration. Methods: Today, PRF is available in both solid and liquid forms with an average resorption period of roughly 2 weeks. While various research endeavors have attempted to utilize Solid-PRF as a barrier membrane in guided bone regeneration (GBR) and various other applications, its two-week resorption period has limited its use as a solo “barrier” membrane owing to its faster-than-ideal resorption properties. Results: Recent studies have demonstrated that by heating and denaturing Liquid-PRF/albumin, the resorption properties of the heated albumin gel could be extended from 2 weeks to 4–6 months by utilizing the Bio-Heat technology. This emerging technology was given the working name ‘extended-PRF’ or e-PRF, with many clinical indications being proposed for further study. Numerous clinicians have now utilized extended-PRF (e-PRF) membranes as a substitute for collagen barrier membranes in various clinical applications, such as guided tissue/bone regeneration, recession coverage, and lateral window sinus lifts. Conclusions: This two-part case series paper aims to first illustrate the evolution of techniques developed taking advantage of this new technology in clinical practice for alveolar ridge preservation. This includes four different methods of fabrication of e-PRF along with its application in clinical practice. This article discusses the clinical outcomes, including the advantages/disadvantages of utilizing each of the four separate techniques to prepare and utilize e-PRF membranes for ridge preservation. Full article

Trabecular Metal^TM (TM) dental implants comprise a tantalum (Ta)-based biomimetic open-cell structure designed to replicate the structural, functional, and physiological properties of cancellous bone. Yet, the current literature primarily focuses on the evaluation of osseointegration outcomes surrounding TM implants in uncompromised bone environments and/or brief periods of observation in pre-clinical models. In addition, the performance of TM implants in bony defect environments reconstructed with allogenic grafts and bioactive molecules, such as platelet-rich fibrin (PRF), has not been thoroughly investigated. This longitudinal, randomized clinical trial comprised patients presenting with completely edentulous maxillaries. Guided Bone Regeneration (GBR) was performed using a cortico-cancellous allograft/PRF agglomerate. After 26 weeks, bone biopsies were obtained, followed by the insertion of a TM implant, after which patients were allowed to heal for 52 weeks for assessment of osseointegration. Qualitatively, histomicrographs at 26 weeks confirmed the presence of newly formed bone extending from the periphery of defects and along the direct surface of the allograft. TM implant biopsies at 52 weeks demonstrated osseointegration with bone ongrowth and ingrowth at the interconnected, porous trabecular region. These histological characteristics were consistent across all patients. No metal debris was detected, and the TM implants maintained their porous structure throughout the study period. TM implants placed in PRF-augmented allograft-reconstructed maxillae fostered a conducive environment for osseointegration. By leveraging the open-cell Ta structure, robust new bone formation was achieved without signs of adverse tissue reactions. Full article

Extended platelet-rich fibrin (e-PRF) combines the prolonged resorption properties of heat-coagulated platelet-poor plasma (PPP), becoming an albumin gel (Alb-gel) that is mixed back with the respective native cell-rich buffy coat layer (BC), i.e., concentrated PRF (C-PRF). E-PRF or Alb-PRF is utilized as a barrier membrane in various clinical applications, such as guided tissue regeneration. The heating of PPP might lower its biological activity, but testing this hypothesis is necessary. To this end, we exposed gingival fibroblasts to the lysates of regular PPP, heated PPP (hPPP), and BC, followed by bulk RNA sequencing. Gingival fibroblasts responded to PPP lysates with a total of 153 up- and 71 down-regulated genes when considering a minimum 3.0-fold log2 expression change and a significance level 2.0 log-10. In sharp contrast, the response to hPPP was characterized by only five up-regulated and five down-regulated genes, clearly indicating that heating almost completely abolished the biological activity of PPP. As expected, BC was more potent than PPP and broadened the spectrum of regulated genes. RT-PCR and immunoassays confirmed the heat sensitivity of PPP as exemplified by IL11 and other genes. Moreover, PPP, but not hPPP, drives the phosphorylation of p65, representing NF-κB signaling. Taken together, these findings extend previous observations that PPP causes a robust response in gingival fibroblasts and also strengthen the hypothesis that this response is heat-sensitive. These operations support the clinical concept of e-PRF by mixing back the heated inactive PPP with the bioactive buffy coat C-PRF layer. Full article

Background and Objectives: This study aimed to evaluate the effects of advanced platelet-rich fibrin (A-PRF+) tissue regeneration therapy on clinical periodontal parameters in non-smokers and smoker patients. The anticipated biological mechanisms of A-PRF+ include stimulating angiogenesis, thereby promoting the formation of new blood vessels, which is essential for tissue healing. Additionally, A-PRF+ harnesses the regenerative properties of platelet-rich fibrin, contributing to the repair and regeneration of periodontal tissues. Materials and Methods: The study was conducted on 55 patients, divided into two groups: non-smoker patients (n = 29) and smoker patients (n = 26). A single operator conducted the surgical procedure. Following the administration of local anesthesia with articaine 4% with adrenaline 1:100,000 precise intracrevicular incisions were made, extending towards the adjacent teeth, until the interproximal spaces, with meticulous attention to conserving the interdental gingival tissue to the greatest extent possible. Extended, full-thickness vestibular and oral flaps were carefully lifted, and all granulation tissue was meticulously removed from the defect without altering the bone contour. After debridement of the defects, A-PRF+ was applied. BOP (bleeding on probing), PI (plaque index), CAL (clinical attachment loss), and probing depth (PD) were determined at baseline and six months post-surgery. Results: Significant reductions were observed in PD and CAL after six months. In the non-smokers group, PD decreased from 7.0 ± 1.0 mm to 3.1 ± 0.1 mm (p < 0.001), while in the smokers group, PD decreased from 6.9 ± 1.1 mm to 3.9 ± 0.3 mm (p < 0.001). CAL decreased in the non-smokers group from 5.8 ± 0.7 mm to 2.6 ± 0.2 mm and from 5.7 ± 0.9 mm to 3.2 ± 0.2 mm (p < 0.001) in smokers. Notably, the reductions in CAL and PD were statistically more significant in the non-smokers group. Conclusions: Even though the clinical periodontal improvements were considerable in smoker patients, they did not reach the level observed in non-smoker patients. Full article

In dental implantology, alveolar ridge preservation (ARP) has emerged as a standard technique to address dimensional changes that affect alveolar ridge morphology following tooth loss. Various alternative graft materials, including xenografts, alloplasts, and allografts, have been effectively employed in fresh extraction sites for ARP. Current evidence suggests that these materials primarily serve as bio-scaffolds, which are slowly incorporated, thus necessitating a waiting period of at least 4–6 months before implant placement. Consequently, the ARP technique extends the overall duration of implant treatment by several months. Recently, the incorporation of a form of autologous platelet concentrate, known as platelet-rich fibrin (PRF), has been advocated in conjunction with ARP as a method of bioenhancement of soft- and hard-tissue healing and regeneration. PRF contains platelet-derived growth factors, hormones, and bioactive components like cytokines that have demonstrated the ability to stimulate angiogenesis and tissue regeneration throughout all phases of wound healing. Additionally, the concentration of leukocytes present in the PRF matrix plays a vital role in tissue healing and regeneration as part of the osteoimmune response. The reported advantages of incorporating autogenous PRF platelet concentrates during ARP encompass reduced healing time, improved angiogenesis and bone regeneration, socket sealing through the fibrin matrix, antibacterial properties, and decreased post-extraction pain and infection risk. Therefore, the objective of this paper is to review the existing evidence regarding the application of PRF in alveolar ridge preservation (ARP) following tooth extraction. Two clinical case studies are presented, wherein ARP was enhanced with PRF, followed by implant placement within a relatively short period of 8 weeks. These cases serve as further proof of concept for supporting the adjuvant use of PRF to enhance healing and accelerate implant placement after ARP. Full article

In implant dentistry, large vertical and horizontal alveolar ridge deficiencies in mandibular and maxillary bone are challenges that clinicians continue to face. One of the limitations of porous blocks for reconstruction of bone in large defects in the oral cavity, and in the musculoskeletal system, is that fibrin clot does not adequately fill the interior pores and does not persist long enough to accommodate cell migration into the center of the block. The objective of our work was to develop a gelatin-based gel incorporating platelet-rich plasma (PRP) lysate, to mimic the role that a blood clot would normally play to attract and accommodate the migration of host osteoprogenitor and endothelial cells into the scaffold, thereby facilitating bone reconstruction. A conjugate of gelatin (Gtn) and hydroxyphenyl propionic acid (HPA), an amino-acid-like molecule, was commended for this application because of its ability to undergo enzyme-mediated covalent cross-linking to form a hydrogel in vivo, after being injected as a liquid. The initiation and propagation of cross-linking were under the control of horseradish peroxidase and hydrogen peroxide, respectively. The objectives of this in vitro study were directed toward evaluating: (1) the migration of rat mesenchymal stem cells (MSCs) into Gtn–HPA gel under the influence of rat PRP lysate or recombinant platelet-derived growth factor (PDGF)-BB incorporated into the gel; (2) the differentiation of MSCs, incorporated into the gel, into osteogenic cells under the influence of PRP lysate and PDGF-BB; and (3) the release kinetics of PDGF-BB from gels incorporating two formulations of PRP lysate and recombinant PDGF-BB. Results: The number of MSCs migrating into the hydrogel was significantly (3-fold) higher in the hydrogel group incorporating PRP lysate compared to the PDGF-BB and the blank gel control groups. For the differentiation/osteogenesis assay, the osteocalcin-positive cell area percentage was significantly higher in both the gel/PRP and gel/PDGF-BB groups, compared to the two control groups: cells in the blank gels grown in cell expansion medium and in osteogenic medium. Results of the ELISA release assay indicated that Gtn–HPA acted as an effective delivery vehicle for the sustained release of PDGF-BB from two different PRP lysate batches, with about 60% of the original PDGF-BB amount in the two groups remaining in the gel at 28 days. Conclusions: Gtn–HPA accommodates MSC migration. PRP-lysate-incorporating hydrogels chemoattract increased MSC migration into the Gtn–HPA compared to the blank gel. PRP-lysate- and the PDGF-BB-incorporating gels stimulate osteogenic differentiation of the MSCs. The release of the growth factors from Gtn–HPA containing PRP lysate can extend over the period of time (weeks) necessary for bone reconstruction. The findings demonstrate that Gtn–HPA can serve as both a scaffold for cell migration and a delivery vehicle that allows sustained and controlled release of the incorporated therapeutic agent over extended periods of time. These findings commend Gtn–HPA incorporating PRP lysate for infusion into porous calcium phosphate blocks for vertical and horizontal ridge reconstruction, and for other musculoskeletal applications. Full article

The platelet-rich fibrin–like matrix (PRFM) is usually prepared onsite and immediately used for regenerative therapy. Nonetheless, to meet the clinical necessity of preserving the PRFM without quality deterioration, we developed a method for preparation of PRFMs from short-term-stored whole blood (WB) samples. In this study, to evaluate the practical expiration date of storage, we extended the storage time of WB samples from 2 to 7 days and assessed the quality of the resulting PRFMs. WB samples collected with acid-citrate-dextrose were stored with gentle agitation at ambient temperature. To prepare PRFMs, the stored WB samples were mixed with CaCl₂ in glass tubes and centrifuged. Fibrin fiber networks, CD41 and CD62P expression, and Platelet Derived Growth Factor-BB (PDGF-BB) levels were examined by scanning electron microscopy (SEM), flow cytometry, and an Enzyme-Linked ImmunoSorbent Assay (ELISA), respectively. Long-term storage had no significant effect on either blood cell counts or platelet functions tested. The resulting PRFMs were visually identical to freshly prepared ones. PDGF-BB levels did not markedly decrease in a time-dependent manner. However, fibrin fibers gradually became thinner after storage. Although the coagulation activity may diminish, we propose that PRFMs can be prepared—without evident loss of quality—from WB samples stored for up to 7 days by our previously developed method. Full article