OBJECTIVE: Plasma rich in growth factors (PRGF) technology creates blood-derived products with growth factors that promote wound healing and regeneration. The goal of this study was to assess the potential role of PRGF products as wound modulators in trabeculectomy. Our premise is that due to PRGF\'s regenerative and antifibrotic properties, its use in trabeculectomy may produce a more physiological bleb, without altering IOP reduction.
METHODS: A retrospective, longitudinal study was conducted in a Hospital in Portugal. Patients with eyes with open angle glaucoma were included. Trabeculectomy was performed on all patients using PRGF membrane (mPRGF) under the conjunctiva, as adjuvant. Data regarding patients\' demographics and number of medications used, was collected. Intraocular pressure (IOP) before surgery, 8 days, 1 month, 3 month, 6 month, 9 month and 1 year after surgery was recorded. Bleb morphology was classified according to Moorfields Bleb Grading System 6 months after surgery.
RESULTS: Nine eyes of 9 patients were enrolled. Mean age was 71 ± 5.1 years old. Six were male. Mean IOP decreased from 24.0 ± 8.8 mmHg pre-surgery to 12.9 ± 2.6 mmHg at one year follow-up. The number of hypotensive drugs (mean ± SD) was 4.3 ± 0.9 preoperatively and 0.8 ± 1.1 at 1-year. Complete success was defined as IOP equal to or less than 21 mm Hg without ocular hypotensive medications and qualified success as IOP equal to or less than 21 mm Hg with medications. Complete success was 66.7% and qualified success was 100% at 1 year follow-up.
CONCLUSIONS: In our study, trabeculectomy with mPRGF demonstrated both safety and efficacy. Low values of bleb height (1.6 ± 0.8) were recorded. mPRGF could improve wound healing and produce a more well-tolerated, favourable bleb, avoiding antimetabolite complications.

The osteogenic differentiation process, by which bone marrow mesenchymal stem cells and osteoprogenitors transform into osteoblasts, is regulated by several growth factors, cytokines, and hormones. Plasma Rich in Growth Factors (PRGF) is a blood-derived preparation consisting of a plethora of bioactive molecules, also susceptible to containing epigenetic factors such as ncRNAs and EVs, that stimulates tissue regeneration. The aim of this study was to investigate the effect of the PRGF clot formulation on osteogenic differentiation. Firstly, osteoblast cells were isolated and characterised. The proliferation of bone cells cultured onto PRGF clots or treated with PRGF supernatant was determined. Moreover, the gene expression of Runx2 (ID: 860), SP7 (ID: 121340), and ALPL (ID: 249) was analysed by one-step real-time quantitative polymerase chain reaction (RT-qPCR). Additionally, alkaline phosphatase (ALPL) activity determination was performed. The highest proliferative effect was achieved by the PRGF supernatant in all the study periods analysed. Concerning gene expression, the logRGE of Runx2 increased significantly in osteoblasts cultured with PRGF formulations compared with the control group, while that of SP7 increased significantly in osteoblasts grown on the PRGF clots. On the other hand, despite the fact that the PRGF supernatant induced ALPL up-regulation, significantly higher enzyme activity was detected for the PRGF clots in comparison with the supernatant formulation. According to our results, contact with the PRGF clot could promote a more advanced phase in the osteogenic process, associated to higher levels of ALPL activity. Furthermore, the PRGF clot releasate stimulated a higher proliferation rate in addition to reduced SP7 expression in the cells located at a distant ubication, leading to a less mature osteoblast stage. Thus, the spatial relationship between the PRGF clot and the osteoprogenitors cells could be a factor that influences regenerative outcomes.

Currently, autologous platelet concentrates (APCs) are frequently used for soft- and hard-tissue regeneration, not only within the oral cavity, but also extra-orally including chronic wounds, burns, joints, dermatological conditions, among others. The benefits of APCs are largely influenced by the treatment strategy but also their preparation. This paper therefore discusses in detail: the physical properties of blood cells, the basic principles of blood centrifugation, the impact of the centrifugation protocol (rotations/revolutions per minute, g-force, variation between centrifuges), the importance of timing during the preparation of APCs, the impact of the inner surface of the blood tubes, the use/nonuse of anticoagulants within APC tubes, the impact of the patient\'s hematocrit, age, and gender, as well as the important requirements for an optimal centrifugation protocol. All these variables indeed have a significant impact on the clinical outcome of APCs.

Congenital aniridia is a rare bilateral ocular malformation characterized by the partial or complete absence of the iris and is frequently associated with various anomalies, including keratopathy, cataract, glaucoma, and foveal and optic nerve hypoplasia. Additionally, nearly 50% of individuals with congenital aniridia experience symptoms of ocular dryness. Traditional treatment encompasses artificial tears and autologous serum. This study aimed to assess the effectiveness and safety of using platelet rich in growth factors (PRGF) plasma in patients with congenital aniridia and ocular dryness symptoms.
METHODS: The included patients underwent two cycles of a 3-month PRGF treatment. At 6 months, symptomatology was evaluated using the OSDI and SANDE questionnaires, and ocular surface parameters were analyzed.
RESULTS: The OSDI and SANDE values for frequency and severity demonstrated statistically significant improvements (p < 0.05). Ocular redness, corneal damage (corneal staining), and tear volume (Schirmer test) also exhibited statistically significant improvements (p < 0.05). No significant changes were observed in visual acuity or in the grade of meibomian gland loss.
CONCLUSIONS: The use of PRGF in patients with congenital aniridia and ocular dryness symptoms led to significant improvements in symptomatology, ocular redness, and ocular damage. No adverse effects were observed during the use of PRGF.

Autologous platelet concentrates (APCs) applied alone or combined with other biomaterials are popular bioactive factors employed in regenerative medicine. The main biological rationale of using such products is to concentrate blood-derived growth factors and cells into the wound microenvironment to enhance the body\'s natural healing capacity. First-generation APC is represented by platelet-rich plasma (PRP). While different protocols have been documented for PRP preparation, they overall consist of two cycles of centrifugation and have important limitations related to the use of an anticoagulant first and an activator afterward, which may interfere with the natural healing process and the release of bioactive molecules. The second generation of platelet concentrates is represented by leukocyte and platelet-rich fibrin (L-PRF). L-PRF protocols involve a single centrifugation cycle and do not require the use of anticoagulants and activators, which makes the preparation more straight forward, less expensive, and eliminates potential risks associated with the use of activators. However, since no anticoagulant is employed, blood undergoes rapid clotting within the blood collection tube; hence, a timely management of L-PRF is crucial. This review provides an overview on the most documented protocols for APC preparations and critically discusses the main differences between first- and second-generation APCs in terms of cell content, protein release, and the formation of a 3D fibrin network. It appears evident that the inconsistency in reporting protocol parameters by most studies has contributed to conflicting conclusions regarding the efficacy of different APC formulations and has significantly limited the ability to interpret the results of individual clinical studies. In the future, the use of a standardized classification system, together with a detailed reporting on APC protocol parameters is warranted to make study outcomes comparable. This will also allow to clarify important aspects on the mechanism of action of APCs (like the role of leukocytes and centrifugation parameters) and to optimize the use of APCs in regenerative medicine.

In the past decades, personalized regenerative medicine has gained increased attention. Autologous platelet concentrates (APCs) such as PRP, PRGF, and L-PRF, all serving as a source of a large variety of cells and growth factors that participate in hard and soft tissue healing and regeneration, could play a significant role in regenerative periodontal procedures. This narrative review evaluated the relative impact of APCs in alveolar ridge preservation, sinus floor augmentation, and the regeneration of bony craters around teeth, both as a single substitute or in combination with a xenograft. L-PRF has a significant beneficial effect on alveolar ridge preservation (bone quality). The data for PRGF are less convincing, and PRP is controversial. L-PRF can successfully be used as a single substitute during transcrestal (≥3.5 mm bone gain) as well as 1-stage lateral window sinus floor elevation (>5 mm bone gain). For PRGF and especially PRP the data are very scarce. In the treatment of bony craters around teeth, during open flap debridement, L-PRF as a single substitute showed significant adjunctive benefits (e.g., >PPD reduction, >CAL gain, >crater depth reduction). The data for PRP and PRGF were non-conclusive. Adding PRP or L-PRF to a xenograft during OFD resulted in additional improvements (>PPD reduction, >CAL gain, >bone fill), for PRGF no data were found. Autologous platelet concentrates demonstrated to enhance bone and soft tissue healing in periodontal regenerative procedures. The data for L-PRF were most convincing. L-PRF also has the advantage of a greater simplicity of production, and its 100% autologous character.

The infrapatellar branch of the saphenous nerve (SN) is a widely described anatomic and functional structure; however, its relevance in daily clinical practice is underestimated. All surgical procedures performed on the anteromedial aspect of the knee are associated with a risk of iatrogenic injury to this nerve, including knee arthroscopy, knee arthroplasty, tibial nailing, etc. We present the case of a saphenous nerve neuroma after treatment with radiofrequency thermal ablation due to a knee pain problem. After conducting an anaesthetic suppression test, we decided to perform a denervation of the medial saphenous nerve in Hunter\'s canal. We performed surgery on the anteromedial aspect of the knee. The distal end of the medial SN was coagulated with a bipolar scalpel. The proximal end of the nerve was released proximally, and a termino-lateral suture was made at the free end of the nerve after creating an epineural window to inhibit its growth. A double crush was produced proximally to the suture site to create a grade II-III axonal injury. Autologous plasma rich in growth factors (PRGF) was used to reduce potential post-surgical adhesions and to stimulate regeneration of the surgical lesions. One year after surgery, the patient was living a completely normal life.

The treatment of chondral and osteochondral defects is challenging. These types of lesions are painful and progress to osteoarthritis over time. Tissue engineering offers tools to address this unmet medical need. The use of an autologous cartilage construct consisting of hyaline cartilage chips embedded in plasma rich in growth factors (PRGF) has been proposed as a therapeutic alternative. The purpose of this study was to dig into the potential mechanisms behind the in vitro remodelling process that might explain the clinical success of this technique and facilitate its optimisation. Chondrocyte viability and cellular behaviour over eight weeks of in vitro culture, type II collagen synthesis, the dual delivery of growth factors by hyaline cartilage and PRGF matrix, and the ultrastructure of the construct and its remodelling were characterised. The main finding of this research is that the cartilage fragments embedded in the three-dimensional PRGF scaffold contain viable chondrocytes that are able to migrate into the fibrin network, proliferate and synthesise extracellular matrix after the second week of in vitro culture. The characterization of this three-dimensional matrix is key to unravelling the molecular kinetics responsible for its efficacy.

The present study evaluates the ability of a novel plasma rich in growth factors (PRGF) membrane with improved optical properties to reduce oxidative stress in retinal pigment epithelial cells (ARPE-19 cells) exposed to blue light. PRGF was obtained from three healthy donors and divided into four main groups: (i) PRGF membrane (M-PRGF), (ii) PRGF supernatant (S-PRGF), (iii) platelet-poor plasma (PPP) membrane diluted 50% with S-PRGF (M-PPP 50%), and (iv) M-PPP 50% supernatant (S-PPP 50%). ARPE-19 cells were exposed to blue light and then incubated with the different PRGF-derived formulations or control for 24 and 48 h under blue light exposure. Mitochondrial and cell viability, reactive oxygen species (ROS) production, and heme oxygenase-1 (HO-1) and ZO-1 expression were evaluated. Mitochondrial viability and cell survival were significantly increased after treatment with the different PRGF-derived formulations. ROS synthesis and HO-1 expression were significantly reduced after cell treatment with any of the PRGF-derived formulations. Furthermore, the different PRGF-derived formulations significantly increased ZO-1 expression in ARPE-19 exposed to blue light. The new PRGF membrane with improved optical properties and its supernatant (M-PPP 50% and S-PPP 50%) protected and reversed blue light-induced oxidative stress in ARPE-19 cells at levels like those of a natural PRGF membrane and its supernatant.

The aim of this study was to explore and assess office-based ultrasound-guided intraosseous and intra-articular infiltrations of plasma rich in growth factors (PRGF) in patients with moderate and severe knee osteoarthritis (KOA). Seventy-nine patients (30 women and 49 men) with grade 3-4 KOA according to the Kellgren-Lawrence classification participated in the study. All patients were treated with a minimally invasive technique using local anesthesia WALANT (wide-awake local anesthesia no tourniquet) in the ambulatory setting. A PRGF intra-articular infiltration and two intraosseous infiltrations in the tibial plateau and femoral condyle were performed weekly for a total of three sessions. The evaluation of the results was carried out using knee injury and osteoarthritis outcome score (KOOS) at baseline and post-treatment. After a follow-up period of 11 months (median) [interquartile range, 7-14], all the KOOS domains showed statistically significant improvement (p < 0.001). Moreover, 88% of the patients showed a pain reduction of at least 10 points (minimally clinically important improvement) from pre- to post-treatment. Our retrospective study using the in-office procedure of ultrasound-guided combination of intra-articular and intraosseous infiltrations of PRGF is a safe and efficacious approach for the treatment of grade 3-4 knee osteoarthritis.