Scientific articles

Chronic low-intensity inflammation is emerging as a potential key mechanism in diseases that were previously considered degenerative, such as tendinopathies, osteoarthritis and intervertebral disc disease. This new approach recognises the role of structures such as the subchondral bone in knee osteoarthritis and the vertebral endplate in disc disease. In this sterile inflammatory context, plasma rich in growth factors (PRGF) a specific type of platelet-rich plasma (PRP) without leucocytes and activated with calcium chloride, has emerged as a promising therapy that exhibits reparative, anti-inflammatory, immunomodulatory, analgesic and antifibrotic properties yet with varied clinical outcomes due to specific patient's physiopathology, product variability and different protocols of application. Its action is based on the regenerative potential of several proteins stemmed from platelets, plasma biomolecules, as well as the fibrin matrix, which acts as a dynamic biological system. Several in vitro and in vivo studies associate the analgesic effect of PRPs with the inhibition of the NF-kappaB pathway in damaged cells, and the presence of endocannabinoids, which reduce nociceptor excitability, with anti-apoptotic and trophic effects at the tissue level. However, variability in PRP preparation and application methods, as well as patient-specific factors, makes it difficult to compare the large heterogeneous clinical outcomes stemmed from the myriad PRP preparation methods and the varied modalities for their application. This review is focused on analysing the latest clinical evidence on PRGF in the treatment of chronic low-intensity inflammation of musculoskeletal disorders, its role in reducing chronic pain, and the limitations of this type of biological therapy.

Introduction Even though the cornea is one of the most widely transplanted solid tissues, it is estimated that approximately 98% of patients requiring a transplant lack access to this sight-saving procedure. This critical gap is a direct consequence of a tremendous global donor shortage, highlighting the urgent need for bioengineered alternatives. Despite significant research efforts, creating a functional bioengineered cornea remains a major challenge. The present study investigates a novel biomimetic approach leveraging Plasma Rich in Growth Factors (PRGF) technology in combination with dental pulp stem cells.Material and methodsHuman dental pulp stem cells (hDPSCs) were isolated, characterized, and differentiated into epithelial, stromal, and endothelial corneal phenotypes. Two distinct types of corneal grafts were developed, categorized by the differentiation stage of the incorporated hDPSCs. The bioengineered constructs consisted of a central bioactive PRGF-fibrin core embedding cells and sandwiched between a trilaminar anterior layer and a posterior cell sheet. The PRGF-derived supernatant was utilized as a medium supplement. The resulting corneal substitutes were evaluated for their optical and rheological properties, as well as cellular viability. Finally, the structural stability and remodeling kinetics of the bioengineered grafts were histologically examined and quantified.ResultsCorneal grafts incorporating undifferentiated hDPSCs exhibited superior elasticity and transparency, while maintaining a higher cell density following the fabrication process. The more pronounced mass reduction observed in these constructs was concomitant with accelerated fibrin degradation and enhanced de novo collagen synthesis.ConclusionBioengineered grafts comprising a central PRGF membrane fibrin core integrated with hDPSCs to mimetically replicate the trilaminar cellular architecture of the cornea, represent a dynamic biomimetic candidate for future clinical applications in corneal transplantation surgery.

INTRODUCTION: Dental autotransplantation has re-emerged as a valuable biological option for tooth replacement in growing patients, mainly due to its ability to preserve the periodontal ligament and maintain alveolar bone. Nevertheless, its potential influence on transverse maxillary development over the long term remains insufficiently explored. The aim of this report was to present a 10-year follow-up of a multidisciplinary rehabilitation, with particular attention to transverse maxillary growth. CASE REPORT: A growing patient who suffered severe dentoalveolar trauma, with loss of all teeth in the upper right quadrant, was treated through a staged multidisciplinary approach. Two unerupted mandibular premolars were autotransplanted to the maxilla, followed by orthodontic alignment and, once growth was completed, implant-supported rehabilitation. Throughout the follow-up period, the transplanted teeth remained functional and vital. One implant developed marginal bone loss after seven years and was successfully replaced after regenerative therapy. At 10 years, both implants and autotransplanted teeth were clinically stable, with CBCT confirming preservation of the regenerated alveolar ridge. RESULTS: Transverse measurements of the maxilla showed similar dimensions between the treated and contralateral sides at both canine and molar levels. These findings suggest that transverse development of the affected hemi-maxilla was not compromised. CONCLUSION: Within the limitations of a single case, this report supports the concept that dental autotransplantation may play a role beyond tooth replacement, potentially contributing to the maintenance of transverse maxillary growth during development. This reinforces its value as a biologically driven strategy in complex cases involving growing patients.

INTRODUCTION: Regenerative medicine offers a sophisticated array of interdependent technologies designed to restore healthy, functional tissue across diverse therapeutic scenarios. In particular, combining biologic matrices with growth factors holds promise for counteracting degenerative processes and restoring tissue function, but translational and standardization challenges limit clinical implementation. AREAS COVERED: This review examines current strategies combining biologic matrices with growth factor-based therapies, focusing on biological, translational, regulatory, and standardization challenges. The literature was identified through a non-systematic search of PubMed, Scopus, and Web of Science using keywords related to regenerative medicine, biomaterials, growth factors, combination products, and standardization, with emphasis on relevant preclinical studies, clinical evidence, and regulatory literature. The review also proposes an algorithm-based treatment framework structured into three operational pillars: (I) Primary Regenerative Target, (II) Bio-functional Configuration, and (III) Phase-Adapted Biological Stimulation. EXPERT OPINION: Pursuing a universal regenerative product is unrealistic because of inherent inter-patient variability. Instead, reproducibility should rely on standardized patient-specific decision pathways that align biological objectives with material engineering, supporting a transition from product-based to algorithm-based standardization.

Cooperation between neutrophils and macrophages is essential to innate immunity. Though they share origins, their distinct roles make them complementary in fighting pathogens and regulating inflammation. However, dysregulation can drive chronic inflammation and autoimmune disease, making therapeutic targeting highly challenging. Broad suppression of these cells is risky; instead, precision strategies are needed to modulate their dual roles in promoting and resolving inflammation. Aging further complicates this balance, as impaired neutrophil and macrophage functions-alongside microbiota alterations-contribute to inflammaging and immune dysfunction. Recent advances in technology offer opportunities to explore these interactions in physiologically relevant contexts, paving the way for targeted interventions that restore immune homeostasis without compromising defense mechanisms. This article highlights the need for nuanced approaches to harness neutrophil-macrophage cooperation for therapeutic benefit.

Platelet-rich plasma (PRP) has emerged as a minimally invasive and widely used therapeutic option within the evolving field of regenerative medicine This retrospective study aimed to characterise plasma rich in growth factors (PRGF), a standardised type of PRP, obtained in a real-world traumatology clinical setting. The consistency of the formulations was also evaluated using three specific classification systems.

BACKGROUND: Pain, decreased quality of life, and functional impairment are common symptoms of knee osteoarthritis (KOA), a degenerative joint disease. Surgery is reserved for advanced cases, and conservative treatment is primarily palliative. Although platelet-rich plasma (PRP) therapy is a novel regenerative strategy, the influence of PRP composition on its effectiveness remains unclear. The aim of this review is to determine whether PRP activation and platelet and leukocyte enrichment are associated with improved pain and functional outcomes in KOA at 6 and 12 months. METHODS: The systematic review included 56 randomized controlled trials (RCTs), involving a total of 5251 patients. Of these, 53 RCTs involving 5031 participants were included in the network meta-analysis. PRP treatments were compared with other nonsurgical interventions and placebo. Primary outcomes included Western Ontario and McMaster Universities Arthritis Index Score (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), and visual analog scale (VAS), while International Knee Documentation Committee Score (IKDC), Lequesne Index, and EuroQol (EQ)-VAS were assessed as secondary outcomes. PRP formulations were categorized on the basis of activation status and Mishra's classification system. Both direct and indirect comparisons were performed using a frequentist network meta-analysis approach. RESULTS: Comparing PRP with different activation states at 6 and 12 months revealed that PRP activation exerted significant benefits in specific KOOS domains at 12 months (KOOS Activities of Daily Living, KOOS Sport and Recreation Function, and KOOS Knee-Related Quality of Life). Generally, the performance of high-platelet PRP was not statistically different from that of low-platelet PRP in most of the assisted questionnaires and domains. Considering activated PRP, no significant variation was detected between Mishra's categories, indicating that increased leukocyte and platelet enrichment ratios confer no additional benefit. CONCLUSIONS: Overall, the data suggest that PRP activation could play a key role in the treatment outcomes of KOA and could compensate for variation in both platelet and leukocyte enrichment. There is a need for RCTs to assess the effect of platelet composition and activation status in the clinical performance of PRP in KOA. LEVEL OF EVIDENCE: Level I, systematic review and network meta-analysis.

PURPOSE: To systematically review and synthesize the available scientific evidence on maximum masticatory forces in adults with complete natural dentition, analyzing differences by anatomical region of the dental arch and by sex, and the influence of the recording protocol and measurement device. METHODS: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO (CRD42024575463). Three databases (PubMed, Scopus, and Web of Science) were searched without date restrictions. Studies reporting maximum bite force values in healthy adults (18-65 years) with complete dentition were included. Methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklists. Quantitative synthesis was performed using a random-effects meta-analysis (DerSimonian-Laird model) to estimate pooled mean values. Heterogeneity was assessed using the I(2) statistic and investigated through subgroup analyses stratified by measurement device, recording protocol (unilateral/bilateral), sex, and dental region, as well as meta-regression for age. RESULTS: A total of 30 studies met the inclusion criteria. Seventeen out of these 30 studies (56.67%) were rated as high quality, 7 (23.33%) as moderate quality, and 6 (20%) as low quality. Meta-analysis confirmed a significant anteroposterior gradient, peaking in the whole dental arch, where the highest mean forces were recorded (males: 874.63 N ; females: 637.22 N ). Significant sexual dimorphism was confirmed across all regions ( p < 0.001 ), with male values in the molar region ( 592 N; 95% CI: 523 - 661 ) consistently exceeding those of females ( 449 N; 95% CI: 382 - 516 ). Meta-regression revealed that a model adjusting for age, sex, and region explains 84.5% of the variance, identifying the measurement device and anatomical location as the dominant drivers of heterogeneity. CONCLUSIONS: Maximum masticatory force varies significantly across dental arch regions and between sexes, with posterior teeth showing higher force values. While sexual dimorphism and age are critical biological modulators, reported values are highly dependent on the measurement device and recording protocol (unilateral vs. bilateral). These findings provide stratified reference values for clinical use while underscoring the need for protocol and technological standardization.

PURPOSE: The objective of this study is to evaluate the efficacy of Plasma rich in growth factors (PRGF) compared to spontaneous healing in alveolar ridge preservation of the aesthetic zone. METHODS: This randomized and controlled clinical trial included 46 patients requiring simple-tooth extraction in the aesthetic zone and subsequent implant placement. The extraction sockets were treated either with PRGF or allowed to heal spontaneously. Postoperative healing was assessed by pain, Landry's soft tissue healing index, and inflammation index at 3, 7, and 15 days after tooth extraction. Histomorphometric bone regeneration was evaluated in biopsies harvested after 12 weeks of healing. Dimensional alveolar ridge measurements were performed at baseline and 12 weeks. Any postoperative complications and adverse effects were registered. Statistical analysis was performed to assess the differences between the study groups. RESULTS: PRGF significantly enhanced postoperative healing, as evidenced by statistically significant reductions in pain on day 3 (p = 0.036) and improved soft tissue healing on days 3 (p = 0.047), 5 (p = 0.012), and 7 (p = 0.027). No significant differences were observed between groups regarding postoperative inflammation. The new bone formation was significantly improved with PRGF treatment (p = 0.024), with a median of 36.1% (range: 15.8% to 58.9%) in the control group compared to 48.7% (range: 31.9% to 92.3%) in the PRGF group. PRGF contributed to improved dimensional stability of the alveolar ridge at 12 weeks. CONCLUSION: PRGF improved healing following tooth extraction by promoting soft tissue healing and reducing postoperative pain. Additionally, it enhanced bone regeneration and contributed to better preservation of the alveolar ridge.

BACKGROUND: Glaucoma, a neurodegenerative disease often linked to elevated intraocular pressure (IOP) and trabecular meshwork (TM) dysfunction, involves oxidative stress and fibrosis. This in vitro study evaluated the impact of various Plasma Rich in Growth Factors (PRGF-Endoret(R)) eye drops formulations, differing in platelet and plasma concentrations, on oxidative stress and fibrotic responses in primary human trabecular meshwork cells (TMCs). METHODS: TMCs were exposed to hydrogen peroxide (H(2)O(2)) to induce oxidative stress and transforming growth factor beta-2 (TGF-beta2) to stimulate fibrotic conditions. Protective and reversal effects of PRGF formulations (1-2, 1-4, 1-6, 2-4 L, and 2-6 L) were assessed by measuring reactive oxygen species (ROS), cell viability, extracellular matrix (ECM) components (glycosaminoglycans, hyaluronan), and fibrotic markers (alpha-smooth muscle actin, collagen I, fibronectin) at both protein and gene expression levels. RESULTS: All PRGF formulations significantly protected against and reversed H(2)O(2)-induced oxidative stress. Similarly, PRGF treatments effectively counteracted TGF-beta2-induced fibrotic differentiation by reducing ECM deposition and the expression of alpha-SMA, collagen I, and fibronectin. The standard PRGF formulation (1-2) demonstrated comparable efficacy to formulations with higher platelet or plasma concentrations. CONCLUSIONS: These in vitro results indicate that PRGF eye drops possess notable antioxidant and antifibrotic properties in TMCs, suggesting its potential as a therapeutic intervention to preserve trabecular meshwork function and potentially lower intraocular pressure in glaucoma. The established 1-2 PRGF formulation appears to be a robust option for mitigating key cellular processes implicated in glaucoma pathogenesis. Further in vivo studies and IOP models are essential to validate these findings and elucidate the underlying therapeutic mechanisms.