Objective: This review comprehensively examined the emerging role of exosomes derived from periodontal ligament stem cells (PDLSC-Exos) in regenerative medicine and dentistry, with a particular focus on their therapeutic potential in periodontitis—a prevalent inflammatory disease characterized by the progressive destruction of periodontal tissues. Methods: An initial search on Scopus, Web of Science, and PubMed using terms associated with exosomes (i.e., exosomes, exosomal, extracellular vesicles, and EVs) and periodontal ligament stem cells without any limitation of publication year and field of study was performed on October 31st, 2024. Results: PDLSC-Exos demonstrated significant therapeutic efficacy in both bone and periodontal regeneration as well as various medical conditions through the enhancement of cellular proliferation, osteoblast differentiation, and the modulation of inflammatory responses. These exosomes function by regulating miRNA and activating essential signaling pathways, thereby facilitating periodontal/bone regeneration, angiogenesis, and tissue repair in disorders such as periodontitis, OTM, and skeletal bony defects. Furthermore, they exhibited anti-inflammatory properties, leading to improved outcomes under inflammatory conditions such as periodontitis, IBD, and MS. Moreover, PDLSC-Exos played a role in anti-microbial and anti-cancer interventions, demonstrating their diverse applicability. Conclusion: The cell-free nature of these therapeutic agents makes PDLSC-Exos a versatile and promising tool for regenerative medicine and immune system regulation. The cell-free nature of these therapeutic agents positions PDLSC-Exos as a promising and adaptable instrument for regenerative medicine and immune system modulation. Clinical relevance: PDLSC-Exos offer a promising acellular therapy for periodontal regeneration, overcoming limitations of cell-based approaches by enhancing tissue repair, modulating inflammation, and improving clinical translation in regenerative medicine and dentistry.

Nearly three decades have now passed since autologous platelet concentrates (APCs) were introduced into clinical practice. Harnessing the body's innate intrinsic capacity for healing, the concepts of platelet‐rich plasma (PRP) and platelet‐rich fibrin (PRF) emerged to concentrate growth factors and cells at supra‐physiological levels. Nearly three decades ago, Professor Robert Marx demonstrated that PRP—obtained via centrifugation of whole blood with anti‐coagulants—could accelerate healing across a wide range of indications in both dentistry and medicine. Subsequent research showed that eliminating anti‐coagulants, leading to the development of PRF, resulted in an even more natural and faster healing process. In dentistry, APCs have been consistently shown to accelerate healing of both soft and hard tissues, either as standalone treatments or in combination with other biomaterials. PRF, in particular, has demonstrated benefits within several dental applications, spanning from root coverage, periodontal regeneration of intra‐bony and furcation defects, ridge preservation, third molar extraction healing, sinus grafting, guided bone regeneration (GBR), and peri‐implant soft tissue healing. Beyond dentistry, PRF has also proven effective in various medical indications—improving outcomes in the treatment of diabetic ulcers, managing joint pain and cartilage degradation in sports medicine, and enhancing outcomes in esthetic medicine. This review highlights the evolution of APCs, with a focus on their clinical applications and recent technological advancements. These include horizontal centrifugation techniques for PRF and more refined protocols for producing concentrated PRF (C‐PRF). Lastly, the article introduces extended‐PRF (e‐PRF) membranes, created through heat‐induced albumin denaturation, which prolong membrane degradation from the typical 2–3 weeks to up to 4 months. These innovative e‐PRF membranes, composed of albumin gel and liquid PRF (Alb‐PRF), are now being used as alternatives to collagen membranes in routine dental procedures.

Background: This systematic review investigated the relationship between pre‐operative vitamin D levels and implant osseointegration and implant‐related outcomes. It also assessed studies involving vitamin D supplementation before implant placement. Methods: In vivo experimental and clinical studies published up to May 15, 2025, were reviewed. Out of 151 initially identified publications, 43 met the inclusion criteria. Results: In total, 16 animal and 27 human studies were included. Most animal studies investigated vitamin D supplementation before implant placement (nine studies), whereas six studies explored vitamin D coatings on implant surfaces. Animal models included osteoporosis, diabetes mellitus, ultraviolet (UV) light deficiency, chronic kidney disease‐induced uremia, and orchiectomy. A positive effect was found for vitamin D on implant osseointegration in 13 of the 16 studies. The human studies comprised three case reports, 10 retrospective studies, three prospective case series, eight prospective controlled trials (2–4 cohorts), and three randomized clinical trials (RCTs). Collectively, 22 of the 27 human studies supported a beneficial association between adequate vitamin D levels and improved implant osseointegration or reduced early implant failure. Vitamin D deficiency was associated with up to a fourfold increase in early implant failures. Pre‐surgical supplementation with vitamin D ₃ enhanced implant osseointegration, improved bone‐implant‐contact (BIC), promoted peri‐implant bone preservation, and reduced early implant failures, even among high‐risk populations (i.e., diabetics). When implant‐related parameters such as pocket depths, radiographic marginal bone levels, or implant stability were measured, significantly poorer outcomes were consistently observed in vitamin D‐deficient groups. Conclusions/Clinical Relevance: Evidence from both animal and human studies strongly indicates that vitamin D deficiency impairs both new bone formation and BIC. Supplementation, particularly in patients with systemic conditions, may improve implant osseointegration outcomes. Pre‐operative screening and correction of vitamin D deficiency are recommended to optimize implant success. Additional well‐designed prospective clinical trials and RCTs are needed to further elucidate the extent of the correlation between serum vitamin D deficiency and the risk of implant failure.

Growth factors, including recombinant human bone morphogenetic protein‐2 (rhBMP2), have been clinically utilised for large bone augmentation with good outcomes. Nevertheless, long‐term healing, swelling, safety concerns, and high cost limit their use. Exosomes, nanoscale extracellular vesicles, have emerged as promising regenerative alternatives. This study assessed the osteogenic potential of periodontal‐specific exosomes (Px) on bone marrow mesenchymal stem cells (BMSCs) compared to rhBMP2. Px were morphologically characterised by TEM and quantified via BCA assay. BMSCs were treated with Px at 1:10, 1:50, and 1:100 dilutions (100, 20, and 10 μg/mL) and compared to rhBMP2 (100 ng/mL). Px uptake was evaluated using PKH26 labeling. Functional assays included viability, migration, alkaline phosphatase (ALP) activity, alizarin red (ARS) mineralization, collagen, osteocalcin secretion, and RT‐PCR analysis of osteogenic genes. Px exhibited spheroidal to cup‐shaped morphology and internalisation in BMSCs up to 18 days. Compared to rhBMP2, Px promoted viability (1.14‐fold), migration (1.78‐fold) up to 1.14 and 1.78‐fold, ALP (1.48‐, 4.11‐fold), ARS (1.43‐, 14.71‐fold), collagen (1.40‐, 3.58‐fold), and osteocalcin (1.86‐, 5.2‐fold). Gene expression demonstrated significant upregulation of ALP (1.73‐fold), RUNX2 (1.70‐fold), OCN (1.36‐fold), and OPN (1.35‐fold). Overall, Px significantly enhanced BMSC osteogenesis compared to rhBMP2, highlighting their potential as a cell‐free nanotherapeutic in bone tissue engineering.

Background: Platelet‐rich fibrin (PRF), a second‐generation autologous platelet concentrate, has gained significant interest for its anti‐inflammatory and regenerative characteristics. While its role in tissue healing is well‐recognized, the analgesic potential of PRF remains under‐investigated.Aim: The primary objective of this systematic review was to critically evaluate any pain‐reported outcome of PRF across all medical and dental procedures in human studies. The secondary objective was to also evaluate outcomes regarding swelling reduction with PRF and other patient‐reported outcomes such as quality of life and analgesic consumption in all included studies.Methods: A systematic search of PubMed, Scopus, Web of Science, and Google Scholar databases was performed for comparative clinical studies assessing PRF's influence on postoperative pain. Eligible studies included human clinical trials comparing PRF with non‐PRF controls, with pain‐reported outcomes as the primary outcome. Data on swelling and other patient‐reported outcomes, including analgesic use and quality of life, was also evaluated as a secondary objective; however, studies that evaluated these outcomes alone were excluded. A total of 200 comparative clinical studies were included, covering a diverse range of procedures including third molar extractions, palatal wound healing, mucogingival procedures, periodontal/bone procedures, maxillary sinus lifts, endodontic procedures, orthodontic procedures, oral lesions, alveolar osteitis, oroantral communications, medically induced osteonecrosis of the jaw, temporomandibular joint disorders, orthopedic procedures, facial surgery and aesthetics, and other fields of medicine. However, heterogeneity in PRF preparation methods and outcome measures precluded a meta‐analysis.Results: Almost all studies reported reduced pain levels in the PRF group compared with non‐PRF controls, with additional benefits observed in terms of swelling reduction, decreased analgesic use, and improved patient‐reported outcomes. Importantly, it was observed that procedures that tend to generate the most patient‐reported pain, such as 3rd molar extractions and autogenous soft tissue grafting from the hard palate, generally reported much lower pain scores following PRF use (72%–85% of studies) and significantly reduced postoperative analgesic use (87.5% of studies).Conclusions: The autologous nature of PRF, along with the sustained release of bioactive factors, likely plays a vital role in modulating inflammation and promoting tissue healing, hence enhancing patient comfort and recovery. As PRF continues to gain traction in clinical practice, integrating well‐designed comparative studies with standardized outcome measures will be necessary to completely understand its therapeutic potential and inform evidence‐based guidelines regarding its application.