Plasma Rich In Growth Factors Research Articles

Plasma Rich in Growth Factors in Bone Regeneration: The Proximity to the Clot as a Differential Factor in Osteoblast Cell Behaviour

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.

Improving the mechanical and biological functions of cell sheet constructs: The interplay of human-derived periodontal ligament stem cells, endothelial cells and plasma rich in growth factors

ObjectiveThe aim of this study was to produce and characterize triple-layered cell sheet constructs with varying cell compositions combined or not with the fibrin membrane scaffold obtained by the technology of Plasma Rich in Growth Factors (mPRGF). Materials and methodsHuman primary cultures of periodontal ligament stem cells (hPDLSCs) were isolated, and their stemness nature was evaluated. Three types of triple-layered composite constructs were generated, composed solely of hPDLSCs or combined with human umbilical vein endothelial cells (HUVECs), either as a sandwiched endothelial layer or as coculture sheets of both cell phenotypes. These three triple-layered constructs were also manufactured using mPRGF as cell sheets’ support. Necrosis, glucose consumption, secretion of extracellular matrix proteins and synthesis of proangiogenic factors were determined. Histological evaluations and proteomic analyses were also performed. ResultsThe inclusion of HUVECs did not clearly improve the properties of the multilayered constructs and yet hindered their optimal conformation. The presence of mPRGF prevented the shrinkage of cell sheets, stimulated the metabolic activity and increased the matrix synthesis. At the proteome level, mPRGF conferred a dramatic advantage to the hPDLSC constructs in their ability to provide a suitable environment for tissue regeneration by inducing the expression of proteins necessary for bone morphogenesis and cellular proliferation. ConclusionshPDLSCs’ triple-layer construct onto mPRGF emerges as the optimal structure for its use in regenerative therapeutics. Clinical relevanceThese results suggest the suitability of mPRGF as a promising tool to support cell sheet formation by improving their handling and biological functions.

Efficacy and Safety of Plasma Rich in Growth Factor in Patients with Congenital Aniridia and Dry Eye Disease.

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. 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. 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.

Safety of Plasma Rich in Growth Factors (PRGF) as additive to healthy human sperm samples: a pilot study.

The aim of our study was to assess if the addition of PRGF to healthy human sperm affects its motility and vitality. This was a prospective study, with 44 sperm donors on whom sperm analysis was performed. Nine mL of blood was collected and PRGF was obtained using PRGF-Endoret® technology. The influence of different dilutions of PRGF (5%, 10%, 20%, 40%) applied to 15 sperm donors was compared, and sperm motility was assessed after 30 minutes. In the second part of the study, 29 sperm donors were studied to analyze the influence of 20% dilution of PRGF at 15, 30 and 45 minutes in fresh and thawed sperm samples. Motility was assessed after the addition of PRGF and after analysis each aliquot was frozen. After thawing, concentration and motility were assessed at the same time periods. There were no differences in sperm motility in fresh samples between dilutions of PRGF when assessed 30 minutes after administration, nor between them, nor when compared to the control group immediately prior to treatment. No trend was observed between motility and PRGF dilution in linear regression analysis. There were no significant differences in thawed samples. The administration of 20% PRGF dilution had no effect on sperm motility compared to samples without PRGF. In addition, there was no change in sperm vitality when comparing samples with and without PRGF. More studies focusing on subnormal sperm samples, analyzing different PRGF concentrations and increasing the number of study variables are needed.

Regenerative medicine in pterygium surgery

Aims/Purpose: Pterygium is a frequently occurring eye condition that arises due to excessive cellular growth, resulting in the development of abnormal fibrovascular growth of the conjunctiva. Despite the improvement of surgical techniques, preventing postoperative recurrence continues to be a significant challenge. At present, pterygium excision using conjunctival autograft is the preferred surgical method, however there is no universally accepted technique to completely eliminate the risk of pterygium recurrence. Plasma rich in growth factors (PRGF) is an autologous blood product rich in proteins and growth factors which can be rapidly obtained from patient blood. Clinically, it is an affordable treatment with potentially broad spectrum of applications in ophthalmology especially in the treatment of complex corneal disorders. The aim of this study was to evaluate the efficiency of autologous platelet‐rich plasma in the treatment of advanced pterygium and to compare it to conjunctival autograft technique.Methods: A total of 26 patients (31 eyes) with advanced pterygium were included in this study. Mean BCVA was 0.7. Patients were divided into 2 groups according to the surgical technique used: PRGF group (16 eyes) and conjunctival autograft group (15 eyes). All patients underwent excision of pterygium followed by closure of the bare sclera either by PRGF or conjunctival autograft. Solid PRGF was either just placed on the corneal surface or sutured with 2 nodes of 10–00 nylon suture at conjunctiva. If necessary, the procedure was repeated. All patients had corneal OCT scan and photo before the treatment and during the follow up. Patients were followed at 2, 6, 12 and 18 months after the procedure.Results: The mean surgery time was shorter in PRGF group (15.0 ± 2 min) compared to conjunctival autograft group (35.0 ± 5 min) (p = 0.001). Mean BCVA improved to 0.8 in both groups. The recurrence was observed in 2 eyes of conjunctival autograft group, while none of the eyes showed recurrence in PRGF group. Graft loss was observed in 2 cases in PRGF group and in 1 eye in conjunctival autograft group. None of the patients reported general or local side effects of the treatment.Conclusions: PRGF is a simple, fast, reliable and effective therapeutic tool to promote wound healing and prevent recurrence after advance pterygium excision.

A novel effect of plasma rich in growth factors in the small leucine‐rich proteoglycans regulation in trabecular meshwork

Aims/Purpose: To analyse the effect of plasma rich in growth factors (PRGF) on the activity of small leucine‐rich proteoglycans (SRLPs) involved in extracellular matrix regulation in a trabecular meshwork fibrosis in vitro model.Methods: Trabecular meshwork cells were obtained from cadaveric donors in collaboration with the Blood and Tissue Centre of the Principality of Asturias (CEImPA2022.359). The cells were exposed to TGFβ2, which induces the expression of fibrosis markers. After 24 h in the presence of TGFβ2, the cells were treated with PRGF or human serum (control group) for 7 days. After the treatment period, samples were processed for immunocytochemistry or gene expression analysis by qPCR. Immunocytochemical techniques were used to examine the markers α‐sma, collagen I and collagen IV markers. The gene expression analysis included the genes lumican (LUM), decorin (DCN), biglycan (BGN) and fibromodulin (FMOD).Results: The induction of fibrosis in trabecular meshwork cells, characterized by an increase in extracellular matrix components such as α‐sma, collagen I and collagen IV, led to an increase in the expression of several SRLPs analysed, such as lumican, decorin, biglycan and fibromodulin. Treatment with PRGF for 7 days significantly reduced the expression of lumican, decorin and biglycan. In contrast, fibromodulin expression levels were slightly increased in the PRGF‐treated group.Conclusions: SRLPs play an important role in the regulation of the extracellular matrix in several ocular tissues. In glaucoma, altered expression of SRLPs such as lumican, decorin and biglycan leads to a glaucomatous phenotype in animal models. Changes in the expression of SRLPs have also been reported in the aqueous humour of glaucoma patients. PRGF treatment regulates the expression of SRLPs, as well as the expression and deposition of other fibrotic markers, and may promote aqueous humour flow and intraocular pressure control.

Infiltration of Plasma Rich in Growth Factors for the Treatment of Temporomandibular Joint Disorders: A Comprehensive Review

Infiltration of Plasma Rich in Growth Factors for the Treatment of Temporomandibular Joint Disorders: A Comprehensive Review

Efficacy of plasma rich in growth factors (PRGF) in stage 1 neurotrophic keratitis.

Efficacy of plasma rich in growth factors (PRGF) in stage 1 neurotrophic keratitis.

The autologous chondral platelet-rich plasma matrix implantation. A new therapy in cartilage repair and regeneration: macroscopic and biomechanical study in an experimental sheep model.

Articular cartilage injuries are a severe problem, and the treatments for these injuries are complex. The present study investigates a treatment for full-thickness cartilage defects called Autologous Chondral Platelet Rich Plasma Matrix Implantation (PACI) in a sheep model. Chondral defects 8 mm in diameter were surgically induced in the medial femoral condyles of both stifles in eight healthy sheep. Right stifles were treated with PACI and an intraarticular injection with a plasma rich in growth factors (PRGF) solution [treatment group (TRT)], while an intraarticular injection of Ringer's lactate solution was administered in left stifles [Control group (CT)]. The limbs' function was objectively assessed with a force platform to obtain the symmetry index, comparing both groups. After 9 and 18 months, the lesions were macroscopically evaluated using the International Cartilage Repair Society and Goebel scales. Regarding the symmetry index, the TRT group obtained results similar to those of healthy limbs at 9 and 18 months after treatment. Regarding the macroscopic assessment, the values obtained by the TRT group were very close to those of normal cartilage and superior to those obtained by the CT group at 9 months. This new bioregenerative treatment modality can regenerate hyaline articular cartilage. High functional outcomes have been reported, together with a good quality repair tissue in sheep. Therefore, PACI treatment might be a good therapeutic option for full-thickness chondral lesions.

Supernatant of activated platelet-rich plasma rejuvenated aging-induced hyposalivation in mouse

Hyposalivation is a common complaint among the elderly, but no established treatment prevents age-induced hyposalivation. Platelet derivatives such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and plasma rich in growth factor (PRGF), are used widely in different areas of regenerative medicine to enhance the wound healing processes. This study examined whether the local injection of the supernatant of activated PRP (saPRP) into the salivary gland (SG) could help prevent aging-induced SG dysfunction and explored the mechanisms responsible for the protective effects on the SG hypofunction. The platelets were separated from the blood of male SD rats (220 ± 20 g). saPRP was manufactured by removing the fibrin clot after activating platelet with calcium ionophore 10 μM (A23187). The total protein and TGF-β1 levels were significantly higher in saPRP than in PRP. Human salivary gland epithelial cell(hSGEC) was treated with saPRP or PRP after senescence through irradiation. The significant proliferation of hSGEC was observed in saPRP treated group compared to irradiation only group and irradiation + PRP group. Cellular senescence, apoptosis, and inflammation significantly reduced in saPRP group. The SG function and structural tissue remodeling by the saPRP were investigated with naturally aged mice. The mice were divided into three groups: 3 months old (3 M), 22 months old (22 M), and 22 months old treated with saPRP (22 M + saPRP). Salivary flow rate and lag time were significantly improved in 22 M + saPRP group compared to 22 M group. The histologic examinations showed the significant proliferation of acinar cell in 22 M + saPRP group. The decrease of senescence, apoptosis, and inflammation observed by western blot in 22 M + saPRP group. The saPRP induced the proliferation of hSGECs, leading to a significant decrease in cellular senescence via decrease inflammation and apoptosis, in vitro. Moreover, the acini cells of the salivary gland were regenerated, and the salivary function increased in aged mice. These results showed that saPRP could be a treatment agent against aging-induced SG dysfunction.

Biological and Adhesive Properties of an Autologous Protein-Based Fibrin Sealant for Ophthalmological Applications.

The aim of this study was to evaluate the biological and adhesive properties of a new autologous sealant based on plasma rich in growth factors (PRGF), named E-Sealant. Conventional PRGF and a commercial fibrin sealant (Tisseel) were included as controls. The hematological and protein content of E-Sealant was determined. Its bioactivity and biocompatibility were tested for human keratocytes (HKs). To evaluate its adhesion and regenerative capacity, E-Sealant was used on an animal model of conjunctival autograft surgery and compared to Tisseel. E-Sealant presented a high growth factor content with levels similar to those of conventional PRGF. E-Sealant induced proliferative and migratory activity on HK cells equivalent to PRGF. Although autologous membranes induced the proliferation of HKs, cells cultured over Tisseel did not adhere nor proliferate. HK cells showed increased number and flattened morphology over PRGF and E-Sealant compared to scarce and round-shape cells detected in Tisseel. Conjunctival autograft glued with E-Sealant adhered successfully, whereas Tisseel application formed irregular clots. During follow-up, both adhesives showed good integration and no dehiscence. However, Tisseel-treated samples presented slightly increased hemorrhage and inflammation. In contrast to Tisseel, E-Sealant-treated autografts presented a continuous layer of non-keratinized stratified squamous epithelium. Inflammatory infiltrates were minimal in E-Sealant-treated conjunctiva, whereas the Tisseel group showed noticeable immune reactions. Unlike Tisseel-treated grafts, E-Sealant presented low immunoreactivity for smooth muscle actin (SMA), suggesting decreased fibrotic tissue formation. E-Sealant presents optimal biological and adhesive properties suitable for use as an ophthalmic glue, with regenerative purposes superior to commercial fibrin sealants. Our study analyzed the characterization and biological activity of a new autologous fibrin sealant in ocular surface cells and in an animal model in which the adhesive and regenerative properties of the fibrin sealant were evaluated.

An effective method for culturing functional human corneal endothelial cells using a xenogeneic free culture medium

Endothelial dysfunction is a leading cause of corneal blindness in developed countries and the only available treatment is the endothelial transplantation. However, the limited availability of suitable donors remains a significant challenge, driving the exploration of alternative regenerative therapies. Advanced Therapy Medicinal Products show promise but must adhere to strict regulations that prohibit the use of animal-derived substances. This study investigates a novel culture methodology using Plasma Rich in Growth Factors (PRGF) as the only source of growth factors for primary cultures of human corneal endothelial cells (CECs). CECs were obtained from discarded corneas or endothelial rings and cultured in two different media: one supplemented with xenogeneic factors and other xenogeneic-free, using PRGF. Comprehensive characterization through immunofluorescence, morphological analyses, trans-endothelial electrical resistance measurements, RNA-seq, and qPCR was conducted on the two groups. Results demonstrate that CECs cultured in the xenogeneic-free medium exhibit comparable gene expression, morphology, and functionality to those cultured in the xenogeneic medium. Notably, PRGF-expanded CECs share 46.9% of the gene expression profile with native endothelium and express all studied endothelial markers. In conclusion, PRGF provides an effective source of xenogeneic-free growth factors for the culture of CECs from discarded corneal tissue. Further studies will be necessary to demonstrate the applicability of these cultures to cell therapies that make clinical translation possible.

Эффективность устранения костных дефектов челюстей

The regenerative medicine methods are being actively developed both in Russia and abroad due to relevance of this direction, especially in the field of the jaw osteoplasty. Autologous, allogeneic and xenoplastic materials, as well as the calcium phosphate ceramics synthetic preparations are conventionally used to normalize and stimulate osteogenesis, however, the treatment outcomes are not always unequivocal. The study was aimed to substantiate the use of the biocomplex consisting of plasma rich in growth factors (PRGF) and xenoplastic material to improve the jawbone osteogenesis efficacy. The study involved 136 patients (105 females and 31 males aged 21–67) divided into four groups based on the method of bone defect restoration. In group 1, no osteoplastic material was used; in group 2, osteoplasty involved the use of the PRGF fibrin gel; in group 3, the Osteobiol Gen-Os material was used; in group 4, osteoplasty involved using the combination of the Osteobiol Gen-Os material and plasma rich in growth factors (PRGF). Computed tomography and digital densitometry were performed before surgery and 3, 6, 12 months after it to assess the dynamics of osteogenesis. A year later restoration of the lost bone tissue volume was reported in 100% of patients in group 4, 70.27% of patients in group 3, 43.47% of patients in group 2, 37.5% of patients in group 1; Fisher's exact test revealed significant differences in the osteoplasty outcomes in groups 3 and 4 (p = 0.00002). There were significant differences in bone density between patients of groups 1 and 2 twelve months after surgery (p = 0.044), between patient of groups 3 and 4 three (p = 0.004), six (p = 0.0001) and 12 (p = 0.0001) months after surgery. The findings show that the method proposed is effective.

The Dual-Responsive Interaction of Particulated Hyaline Cartilage and Plasma Rich in Growth Factors (PRGF) in the Repair of Cartilage Defects: An In Vitro Study.

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.

PRGF Membrane with Tailored Optical Properties Preserves the Cytoprotective Effect of Plasma Rich in Growth Factors: In Vitro Model of Retinal Pigment Epithelial Cells

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.

Office-Based Intraosseous Infiltrations of PRGF as an Effective Treatment for Knee Osteoarthritis: A Retrospective Observational Clinical Study.

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.

O-221 Regenerative endometrial PRGF (plasma rich in growth factors) treatment in patients with thin endometrium, recurrent implantation failure, and recurrent miscarriages: a retrospective, self-controlled, cohort study

Abstract Study question What reproductive outcomes are observed in patients submitted to endometrial PRGF therapy due to thin endometrium (ThE), recurrent implantation failure (RIF) and recurrent miscarriages (RM)? Summary answer Following endometrial PRGF treatment, success rates were significantly increased in ThE and RIF patients, whereas in the RM group pregnancy loss rates were not affected. What is known already Adequate development of a functional endometrium is a prerequisite for successful embryo implantation in ART cycles. In contrast, the management of patients with thin endometrial lining or recurrent implantation failure has been an ongoing challenge with none of the proposed surgical, hormonal, and pharmacological interventions achieving satisfactory results. In recent years, the use of plasma rich in growth factors (PRGF) - successfully applied in other medical fields - has become a novel treatment option in reproductive medicine. It was used experimentally both for ovarian follicle activation and to enhance endometrial receptivity although published studies are small with often contradictory results. Study design, size, duration All consecutive patients (n = 107) who underwent endometrial PRGF treatment (n = 150) in a single, private centre between 2016-2022 were included in this retrospective analysis. Patients were recruited into ThE (n = 64), RIF (n = 36) and RM (n = 7) groups, respectively. Live birth / ongoing pregnancy rates per embryo transfer were compared to success rates obtained in previous embryo transfers preceding the endometrial PRGF intervention. External Ethics Committee approval was obtained for a comparative pilot study including above patient groups. Participants/materials, setting, methods PRGF was obtained by processing the patients’ autologous blood sample in an in-house validated open system. Endometrial PRGF interventions were performed using a thawed PRGF sample with a series of intrauterine instillations (43%) or with a combined approach performing hysteroscopic subendometrial infiltration during early follicular phase (57%). Endometrial preparation was conducted using an artificial hormone replacement protocol with high-dose oral estrogens and vaginal progesterone. Most embryo transfers involved the replacement of a single, vitrified-thawed blastocyst. Main results and the role of chance A total of 107 patients underwent 150 endometrial PRGF treatments and 131 subsequent embryo transfers. Altogether 19 (13%) embryo transfers were cancelled, higher in ThE than in the RIF group (16 vs 7.1%). In the ThE group (64 patients, 98 PRGF cycles and 107 controls), positive pregnancy (41 vs 32%, NS), clinical pregnancy (35 vs 22%, p = 0.049) and ongoing pregnancy/live birth rates (24 vs 4.7%, p &amp;lt; 0.0001) per embryo transfer were significantly higher in the endometrial PRGF treatment group compared to previous embryo transfers. In the RIF group (36 patients, 42 PRGF cycles and 101 controls), positive pregnancy (59 vs 20%, p &amp;lt; 0.0001), clinical pregnancy (44 vs 11%, p &amp;lt; 0.0001) and ongoing pregnancy/live birth rates (33 vs 7.9%, p &amp;lt; 0.0001) per embryo transfer were significantly higher in the endometrial PRGF treatment group compared to previous embryo transfers. In the RM group (7 patients, 10 PRGF cycles and 15 controls), positive pregnancy (50 vs 60%), clinical pregnancy (20 vs 27%) and ongoing pregnancy/live birth rates (0 vs 0%) per embryo transfer were not significantly different and no ongoing pregnancies were achieved. So far, 20 singletons and 1 set of twins have been confirmed to be born from the above PRGF cycles (12 pregnancies still ongoing). Limitations, reasons for caution Heterogeneity of clinical severity between included ThE patients could affect observed reproductive outcomes. The self-controlled design of the study might have influenced the comparison between pre-, and post-intervention pregnancy rates, although this also highlights the poor-prognostic nature of included participants. RM patients were too few to evaluate pregnancy loss rates. Wider implications of the findings This preliminary, retrospective study has shown that regenerative therapy using autologous PRGF is a safe, affordable, and efficient treatment option for ThE and RIF patients. Further randomized studies are warranted, although they are hampered by patient selection issues and the lack of applicable efficient treatment options in the non-intervention group. Trial registration number not applicable

Cellular composition modifies the biological properties and stability of platelet rich plasma membranes for tissue engineering.

Scaffolds should provide structural support for tissue regeneration, allowing their gradual biodegradation and interacting with cells and bioactive molecules to promote remodeling. Thus, the scaffold's intrinsic properties affect cellular processes involved in tissue regeneration, including migration, proliferation, differentiation, and protein synthesis. In this sense, due to its biological effect and clinical potential, Platelet Rich Plasma (PRP) fibrin could be considered a successful scaffold. Given the high variability in commercial PRPs formulations, this research focused on assessing the influence of cellular composition on fibrin membrane stability and remodeling cell activity. The stability and biological effect were evaluated at different time points via D-dimer, type I collagen and elastase quantification in culture media conditioned by Plasma Rich in Growth Factors - Fraction 1 (PRGF-F1), Plasma Rich in Growth Factors - Whole Plasma (PRGF-WP) and Leukocyte-rich Platelet Rich Plasma (L-PRP) membranes, and by gingival fibroblast cells seeded on them, respectively. Ultrastructure of PRP membranes was also evaluated. Histological analyses were performed after 5 and 18 days. Additionally, the effect of fibrin membranes on cell proliferation was determined. According to the results, L-PRP fibrin membranes degradation was complete at the end of the study, while PRGF membranes remained practically unchanged. Considering fibroblast behavior, PRGF membranes, in contrast to L-PRP ones, promoted extracellular matrix biosynthesis at the same time as fibrinolysis and enhanced cell proliferation. In conclusion, leukocytes in PRP fibrin membranes drastically reduce scaffold stability and induce behavioral changes in fibroblasts by reducing their proliferation rate and remodeling ability.

Effects of Combining Plasma Rich in Growth Factors with Different Bone Grafts on Early Bone Healing: An Experimental Study.

To histologically and radiographically investigate the effect of plasma rich in growth factor (PRGF) mixed with bone grafts on ossification in the early period. A total of 12 New Zealand male rabbits (weighing between approximately 2.5 to 3 kg) were included in this study. Subjects were randomly divided into two sets of groups: control and experiment. Autograft, DFDBA (demineralized freeze-dried bone allograft), and DBBM (deproteinized bovine bone mineral) were applied to different defects in the control groups, and autograft + PRGF, DFDBA + PRGF, and DBBM + PRGF were applied in the experimental groups. All subjects were euthanized 28 days after surgery. The volumes of the bone, new connective tissue, and new capillaries were evaluated stereologically, and the bone density in the defects was investigated radiographically. Regarding the stereologic evaluation, the volumes of the bone and capillaries were significantly higher in the experimental groups than in the control groups. In contrast, the connective tissue volume was considerably lower (P < .001, in all groups). Similarly, radiographic examinations showed that the bone density measurements in the experimental groups were higher than in the control groups. However, these differences were statistically significant only between the DFDBA + PRGF and DFDBA groups (P < .011). The present study provides evidence that the addition of PRGF to autograft, DFDBA, and DBBM enhances osteogenesis in the early period compared to using these grafts alone. It also accelerates the remodeling of connective tissue to bone in defects. Int J Oral Maxillofac Implants 2023;38:569-575. doi: 10.11607/jomi.9858.

Development of a new plasma rich in growth factors membrane with improved optical properties.

The aim of the present work was to develop a fibrin membrane using plasma rich in growth factors (PRGF) technology with improved optical properties to be used for the treatment of ocular surface diseases. Blood was drawn from three healthy donors, and the volume of PRGF obtained from each donor was divided into two main groups: i) PRGF or ii) platelet-poor plasma (PPP). Each membrane was then used pure or diluted to 90 %, 80 %, 70 %, 60 % and 50 %. The transparency of each of the different membranes was evaluated. The degradation and morphological characterization of each membrane was also performed. Finally, a stability study of the different fibrin membranes was performed. The transmittance test showed that the fibrin membrane with the best optical characteristics was obtained after removal of platelets and dilution of fibrin to 50 % (50 % PPP). No significant differences (p>0.05) were observed between the different membranes in the fibrin degradation test. The stability test showed that the membrane at 50 % PPP retains its optical and physical characteristics after storage at -20 °C for 1 month compared to storage at 4°C. The present study describes the development and characterization of a new fibrin membrane with improved optical characteristics while maintaining mechanical and biological characteristics. The physical and mechanical properties of the newly developed membrane are preserved after storage for at least 1 month at -20 °C.