An evolutionary history of F12 gene: Emergence, loss, and vulnerability with the environment as a driver.

In the context of macroevolutionary transitions, environmental changes prompted vertebrates already bearing genetic variations to undergo gradual adaptations resulting in profound anatomical, physiological, and behavioral adaptations. The emergence of new genes led to the genetic variation essential in metazoan evolution, just as was gene loss, both sources of genetic variation resulting in adaptive phenotypic diversity. In this context, F12-coding protein with defense and hemostatic roles emerged some 425 Mya, and it might have contributed in aquatic vertebrates to the transition from water-to-land. Conversely, the F12 loss in marine, air-breathing mammals like cetaceans has been associated with phenotypic adaptations in some terrestrial mammals in their transition to aquatic lifestyle. More recently, the advent of technological innovations in western lifestyle with blood-contacting devices and harmful environmental nanoparticles, has unfolded new roles of FXII. Environment operates as either a positive or a relaxed selective pressure on genes, and consequently genes are selected or lost. FXII, an old dog facing environmental novelties can learn new tricks and teach us new therapeutic avenues.

Biochemical and biomechanical characterization of an autologous protein-based fibrin sealant for regenerative medicine.

Accidental events or surgical procedures usually lead to tissue injury. Fibrin sealants have proven to optimize the healing process but have some drawbacks due to their allogeneic nature. Autologous fibrin sealants present several advantages. The aim of this study is to evaluate the performance of a new autologous fibrin sealant based on Endoret®PRGF® technology (E-sealant). One of the most widely used commercial fibrin sealants (Tisseel®) was included as comparative Control. E-sealant´s hematological and biological properties were characterized. The coagulation kinetics and the microstructure were compared. Their rheological profile and biomechanical behavior were also recorded. Finally, the swelling/shrinkage capacity and the enzymatic degradation of adhesives were determined. E-sealant presented a moderate platelet concentration and physiological levels of fibrinogen and thrombin. It clotted 30 s after activation. The microstructure of E-sealant showed a homogeneous fibrillar scaffold with numerous and scattered platelet aggregates. In contrast, Control presented absence of blood cells and amorphous protein deposits. Although in different order of magnitude, both adhesives had similar rheological profiles and viscoelasticity. Control showed a higher hardness but both adhesives presented a pseudoplastic hydrogel nature with a shear thinning behavior. Regarding their adhesiveness, E-sealant presented a higher tensile strength before cohesive failure but their elastic stretching capacity and maximum elongation was similar. While E-sealant presented a significant shrinkage process, Control showed a slight swelling over time. In addition, E-sealant presented a high enzymatic resorption rate, while Control showed to withstand the biodegradation process in a significant way. E-sealant presents optimal biochemical and biomechanical properties suitable for its use as a fibrin sealant with regenerative purposes.

Sleep bruxism and sleep respiratory disorders in children and adolescents: A systematic review.

OBJECTIVE: Sleep bruxism (SB) is a repetitive rhythmic and nonrhythmic activity. It can be a comorbid condition for other disorders, such as sleep breathing disorders (SBD). However, a clear causal link between these factors is yet to be established. Moreover, this relationship is even more unknown in children. Thus, this systematic review aimed to determine the relationship between SB and SBD in children and teenagers and consolidate the current knowledge about the possible association between both phenomena at the pediatric age. MATERIALS AND METHODS: Advanced searches were performed in five electronic databases with the last search updated on February 1, 2023. The methodological quality of the selected studies was analyzed using the quality assessment tool for experimental bruxism studies. RESULTS: Twenty-nine of 6378 articles were selected for detailed analyses. Most articles found a comorbid relationship between SB and SBD, though no study analyzed a temporary relationship. Due to the heterogeneity of the studies, a meta-analysis could not be performed. CONCLUSION: Despite the limitations of this systematic review, it can be concluded that there is an association between SB and SBD in children. However, the level of evidence is low.

Plasma Rich in Growth Factors as an Adjuvant Treatment for the Management of Frontal Fibrosing Alopecia: A Retrospective Observational Clinical Study.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a scarring alopecia in which the exact etiopathogenesis has not been completely elucidated and the available treatments are not very effective. Plasma rich in growth factors (PRGF) has shown to induce folliculogenesis in hair loss related disorders. However, the scientific evidence when facing FFA is scarce. OBJECTIVES: The aim of this study was to retrospectively analyze the adjuvant use of PRGF compared to the conventional treatment in the management of FFA. METHODS: Participants with clinically diagnosed FFA who had been treated with either conventional therapy (Control Group) or conventional therapy combined with PRGF (PRGF Group) were identified from the center's medical records. The clinical assessment was based on the "Frontal Fibrosing Alopecia Severity Score" (FFASS), which was fulfilled during a period of two and 4 years. RESULTS: This study included 118 patients with clinically diagnosed FFA (Control Group: 57 and PRGF Group: 61). No adverse effects related to the treatments were observed. Both treatments showed to halt the steady progression of hair loss compared to baseline. PRGF treatment also induced significant hair regrowth compared to the Control Group. The scalp inflammation was reduced in response to treatments. The FFASS score indicated that PRGF Group improved the symptoms and severity of FFA in a significant manner. CONCLUSIONS: The adjuvant use of PRGF may exert long-term beneficial effects on hair loss reduction and might reduce the symptoms and severity of FFA.

Plasma rich in growth factors versus corticosteroid injections for management of chronic rotator cuff tendinopathy: a prospective double-blind randomized controlled trial with 1 year of follow-up.

BACKGROUND: Rotator cuff tendinopathy (RCT) is a painful and dysfunctional shoulder condition traditionally considered as a degenerative pathology. However, evidence is pointing to immunocompetent cells and activated stromal fibroblasts as the drivers of a nonresolved inflammatory condition in RCT. As potent anti-inflammatory agents, corticosteroid injections have been among the first-line and the most common therapeutic strategies. Recently, another adjuvant therapy to treat musculoskeletal inflammation-driven painful conditions, namely, platelet-rich plasma (PRP), has emerged as safe and effective. The aim of this study was to compare the clinical efficacy of intratendinous injections of plasma rich in growth factors (PRGF) with conventional intratendinous corticosteroid injections on patients with chronic RCT using patient-reported outcome measures. METHODS: A total of 39 patients received PRGF treatment (3 infiltrations, 1 every other week), whereas 40 patients, as a control group, received corticosteroid (3 infiltrations, 1 every other week). Patients were evaluated before treatment and at 3, 6, and 12 months of follow-up using the University of California Los Angeles (UCLA) scale, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), and Constant test. The primary outcome of the study was a 15% superior improvement of the PRGF group compared with the corticosteroid group in the UCLA scale and QuickDASH test at 6 months of follow-up, considering this difference to be clinically relevant. RESULTS: Both PRGF and corticosteroid groups showed significant clinical improvement in the 3 scores at all time points of the study compared with baseline. However, at 6 and 12 months of follow-up, the PRGF group had 22.1% and 21.2% superior improvement of the UCLA test, 14.3% and 13.5% for QuickDASH, and 16.4% and 20.2% for the Constant-Murley test, respectively, compared to the corticosteroid group. CONCLUSIONS: Three PRGF intratendinous injections every other week in patients with chronic rotator cuff tendinopathy show significantly superior and sustained pain-relieving and functional improvements compared with corticosteroid intratendinous injections assessed by 3 patient-reported outcome scales at 6 and 12 months of follow-up.

Advances in Platelet Rich Plasma-Derived Extracellular Vesicles for Regenerative Medicine: A Systematic-Narrative Review.

The use of platelet-rich plasma (PRP) has gained increasing interest in recent decades. The platelet secretome contains a multitude of growth factors, cytokines, chemokines, and other biological biomolecules. In recent years, developments in the field of platelets have led to new insights, and attention has been focused on the platelets' released extracellular vesicles (EVs) and their role in intercellular communication. In this context, the aim of this review was to compile the current evidence on PRP-derived extracellular vesicles to identify the advantages and limitations fortheir use in the upcoming clinical applications. A total of 172 articles were identified during the systematic literature search through two databases (PubMed and Web of Science). Twenty publications met the inclusion criteria and were included in this review. According to the results, the use of PRP-EVs in the clinic is an emerging field of great interest that represents a promising therapeutic option, as their efficacy has been demonstrated in the majority of fields of applications included in this review. However, the lack of standardization along the procedures in both the field of PRP and the EVs makes it extremely challenging to compare results among studies. Establishing standardized conditions to ensure optimized and detailed protocols and define parameters such as the dose or the EV origin is therefore urgent. Further studies to elucidate the real contribution of EVs to PRP in terms of composition and functionality should also be performed. Nevertheless, research on the field provides promising results and a novel basis to deal with the regenerative medicine and drug delivery fields in the future.

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.

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.

In vitro and in vivo Effect of Platelet-Rich Plasma-Based Autologous Topical Serum on Cutaneous Wound Healing.

INTRODUCTION: Skin injury and wound healing is an inevitable event during lifetime. However, several complications may hamper the regeneration of the cutaneous tissue and lead to a chronic profile that prolongs patient recovery. Platelet-rich plasma is rising as an effective and safe alternative to the management of wounds. However, this technology presents some limitations such as the need for repeated blood extractions and health-care interventions. OBJECTIVE: The aim of this study was to assess the use of an endogenous and storable topical serum (ES) derived from plasma rich in growth factors promoting wound healing, and to obtain preliminary data regarding its clinical and experimental effect over ulcerated skin models and patient care. METHODS: Human dermal fibroblast and 3D organotypic ulcerated skin models were used to assess ES over the main mechanisms of wound healing including cell migration, edge contraction, collagen synthesis, tissue damage, extracellular matrix remodeling, cell death, metabolic activity, and histomorphometry analysis. Additionally, 4 patients suffering from skin wounds were treated and clinically assessed. RESULTS: ES promoted dermal fibroblast migration, wound edge contraction, and collagen synthesis. When topically applied, ES increased collagen and elastin deposition and reduced tissue damage. The interstitial edema, structural integrity, and cell activity were also maintained, and apoptotic levels were reduced. Patients suffering from hard-to-heal wounds of different etiologies were treated with ES, and the ulcers healed completely within few weeks with no reported adverse events. CONCLUSION: This preliminary study suggests that ES might promote cutaneous wound healing and may be useful for accelerating the re-epithelization of skin ulcers.

Evolutionary Insight into Immunothrombosis as a Healing Mechanism.

Both invertebrates and vertebrates possess a cluster of immediate and local wound-sealing, pathogen-killing, and tissue healing responses known as immunoclotting and immunothrombosis, respectively, to cope with two life-threatening emergencies, namely, bleeding and microbial invasion. Despite their convergence in function, immunoclotting and immunothrombosis are deployed by different blood cells and intravascular multidomain proteins. In vertebrates, these proteins share some domains with intrinsic chemical affinities useful in generating cooperative networks such as pathogen and damage pattern recognition molecules. Moreover, many of the proteins involved in coagulation and fibrinolysis in humans are multifunctional molecules playing roles in other processes from inflammation to healing and beyond. In our modern society, however, the interaction of activated intravascular allosteric proteins with one another and with blood cells entails vulnerabilities posing a biological paradox: intravascular proteins that locally operate as tissue repair enhancers can nevertheless generate pathogenic processes by acting systemically. In this manuscript, we contextualize and frame the coagulation system and hemostasis through an evolutionary time scale, illustrating their role as dual players in the defense against exsanguination and pathogens while significantly influencing wound healing.

Platelet-Rich Plasma as an Alternative to Xenogeneic Sera in Cell-Based Therapies: A Need for Standardization.

There has been an explosion in scientific interest in using human-platelet-rich plasma (PRP) as a substitute of xenogeneic sera in cell-based therapies. However, there is a need to create standardization in this field. This systematic review is based on literature searches in PubMed and Web of Science databases until June 2021. Forty-one studies completed the selection criteria. The composition of PRP was completely reported in less than 30% of the studies. PRP has been used as PRP-derived supernatant or non-activated PRP. Two ranges could be identified for platelet concentration, the first between 0.14 × 106 and 0.80 × 106 platelets/µL and the second between 1.086 × 106 and 10 × 106 platelets/µL. Several studies have pooled PRP with a pool size varying from four to nine donors. The optimal dose for the PRP or PRP supernatant is 10%. PRP or PRP-derived supernatants a have positive effect on MSC colony number and size, cell proliferation, cell differentiation and genetic stability. The use of leukocyte-depleted PRP has been demonstrated to be a feasible alternative to xenogeneic sera. However, there is a need to improve the description of the PRP preparation methodology as well as its composition. Several items are identified and reported to create guidelines for future research.

Dental Implants Survival After Nasal Floor Elevation: A Systematic Review.

The aim of this work is to assess the clinical outcomes of implants placed after a nasal floor elevation procedure. A systematic review was conducted using 4 electronic databases: MEDLINE (PubMed), Cochrane Library, Directory of Open Access Journals, and Scopus, following the PRISMA (Preferred Reporting Items for Systematic Reviews) statement recommendations to answer the PICO (Population, Intervention, Comparison, Outcome) question: "In patients undergoing dental implant placement in the maxillary anterior region (P), Do implants placed after nasal floor elevation (I) have a different survival (O) from those implants placed without grafting procedures (C)? The study was pre-registered in PROSPERO (CRD42021229479). Included article quality was assessed using the "NIH quality assessment tool", "The Newcastle-Ottawa scale," and "JBI critical appraisal tools for case reports." Twelve articles were finally selected, including 151 patients and 460 implants. The weighted mean follow-up was 32.2 months, and the weighted survival rate after this period was 97.64% (range: 89.2%-100%). No statistical differences could be inferred between the treatments performed in 1- or 2-stage, following a lateral approach or a transcrestal approach or using different grafting materials. A great heterogeneity was found in study design and methodological aspects. For this reason, a quantitative analysis followed by meta-analysis was not possible. Within the limitations of this study, implants placed after a nasal floor elevation present a good survival and a low range of complications. In absence of randomized studies, the level of evidence was low, attending the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) system and based on the study quality level, the strength of evidence attending the SORT (Strength Of Recommendation Taxonomy) was B.

Protein adsorption/desorption dynamics on Ca-enriched titanium surfaces: biological implications.

Calcium ions are used in the development of biomaterials for the promotion of coagulation, bone regeneration, and implant osseointegration. Upon implantation, the time-dependent release of calcium ions from titanium implant surfaces modifies the physicochemical characteristics at the implant-tissue interface and thus, the biological responses. The aim of this study is to examine how the dynamics of protein adsorption on these surfaces change over time. Titanium discs with and without Ca were incubated with human serum for 2 min, 180 min, and 960 min. The layer of proteins attached to the surface was characterised using nLC-MS/MS. The adsorption kinetics was different between materials, revealing an increased adsorption of proteins associated with coagulation and immune responses prior to Ca release. Implant-blood contact experiments confirmed the strong coagulatory effect for Ca surfaces. We employed primary human alveolar osteoblasts and THP-1 monocytes to study the osteogenic and inflammatory responses. In agreement with the proteomic results, Ca-enriched surfaces showed a significant initial inflammation that disappeared once the calcium was released. The distinct protein adsorption/desorption dynamics found in this work demonstrated to be useful to explain the differential biological responses between the titanium and Ca-ion modified implant surfaces.

Development and optimization of a personalized fibrin membrane derived from the plasma rich in growth factors technology.

PURPOSE: To develop and characterize a new type of plasma rich in growth factors (PRGF) membrane for patients in which immune system is involved in the disease etiology. METHODS: Blood from three healthy donors was collected to obtain the different fibrin membranes by PRGF technology. PRGF obtained volumes were activated and divided into two groups: PRGF membrane (mPRGF) obtained after incubation at 37 °C for 30 min (control); and is-mPRGF: mPRGF obtained after incubation for 30 min at 56 °C. The concentration of several growth factors, proteins, immunoglobulin E and the complement activity was determined in the different mPRGF. The proliferative potential of heat-inactivated mPRGF were assayed on keratocytes (HK) and conjunctival fibroblasts (HConF). In addition, morphological and physical features of the inactivated mPRGF were evaluated in contrast to the control mPRGF. RESULTS: Heat-inactivation of the mPRGF preserves the content of most of the growth factors involved in the ocular wound healing while reducing drastically the content of IgE and the complement activity. The heat-inactivated mPRGF conserve the morphological and physical characteristics of the fibrin meshwork in comparison with the control mPRGF. Furthermore, no significant differences were found in the biological activity of the control mPRGF regarding the heat-inactivated mPRGF (is-mPRGF) in any of both ocular cell types evaluated. CONCLUSIONS: The heat-inactivation of the PRGF membranes (is-mPRGF) reduces drastically the content of IgE and complement activity while preserving the content of most of the proteins and morphogens involved in ocular wound healing. Furthermore, the morphological and physical features of the immunosafe mPRGF were also preserved after heat-inactivation.

The Effectiveness of Platelet-Rich Plasma as a Carrier of Stem Cells in Tissue Regeneration: A Systematic Review of Pre-Clinical Research.

Fibrin, as a physiological scaffold, presents many advantages compared to synthetic materials, such as controllable degradation, non-toxic byproducts, and excellent biocompatibility. The use of stem cells along with the biomimicking scaffolds and signalling factors would complete the triad of the tissue engineering approach. In this context, the aim of this narrative review is to compile the current evidence in vitro and in vivo regarding the combination of platelet-rich plasma (PRP) scaffolds and adult stem cells focusing on the regenerative medicine field according to the clinical application. A total of 1,832 articles were identified during the systematic literature search through three databases (Google Scholar, PubMed, and Web of Science). A total of 18 publications reaching the inclusion criteria were finally included in this review. According to the results, the combination of PRP and stem cells improved osteogenic and cartilage regeneration. However, regarding periodontal regeneration conflicting results were reported. Many other pathologies were also investigated, and even though no general conclusions were able to be obtained, most of them supported the superior performance of PRP-based scaffolds seeded with stem cells. Finally, the lack of a comprehensive description of the PRP composition makes it difficult to compare them and to draw robust conclusions. Therefore, an accurate and complete description of the product needs to be detailed in upcoming scientific publications.

Platelet rich plasma in oral and maxillofacial surgery from the perspective of composition.

The application of platelet-rich plasma (PRP) in oral and maxillofacial surgery has been thoroughly studied in the last two decades. Currently, different types of PRP are applied in the clinical practice, being the presence or absence of leukocytes one of the classification criteria. However, there is poor evidence assessing the influence of the PRP composition in their efficacy. In this context, the aim of this narrative review is to compile the existing evidence covering the efficacy of PRP in oral and maxillofacial surgery, starting from a systematic literature search and to qualitatively describe the efficacy outcomes from the composition perspective. According to the results of this review, the application of PRP in oral and maxillofacial surgery is a potential strategy to improve soft- and hard-tissue regeneration, observing differences in the efficacy of PRP depending on its composition and the studied application. P-PRP (the absence of leukocytes) has been more consistent in achieving beneficial effects in alveolar ridge preservation, management of post-extraction complications, bone augmentation and temporomandibular joint disorders. For that, the composition and methodology used to prepare the PRP should be a critical point when evaluating the efficacy of PRP.

Proteomic Characterization of Plasma Rich in Growth Factors and Undiluted Autologous Serum.

Over the last three decades, there has been special interest in developing drugs that mimic the characteristics of natural tears for use it in the treatment of several ocular surface disorders. Interestingly, the composition of blood plasma is very similar to tears. Therefore, different blood-derived products like autologous serum (AS) and plasma rich in growth factors (PRGF) have been developed for the treatment of diverse ocular pathologies. However, scarce studies have been carried out to analyze the differences between both types of blood-derived products. In the present study, blood from three healthy donors was drawn and processed to obtain AS and PRGF eye drops. Then, human corneal stromal keratocytes (HK) were treated with PRGF or undiluted AS. Proteomic analysis was carried out to analyze and characterize the differential protein profiles between PRGF and AS, and the differentially expressed proteins in HK cells after PRGF and AS treatment. The results obtained in the present study show that undiluted AS induces the activation of different pathways related to an inflammatory, angiogenic, oxidative stress and scarring response in HK cells regarding PRGF. These results suggest that PRGF could be a better alternative than AS for the treatment of ocular surface disorders.

Fibrin-Plasma Rich in Growth Factors Membrane for the Treatment of a Rabbit Alkali-Burn Lesion.

The purpose of this work is to describe the use of Fibrin-Plasma Rich in Growth Factors (PRGF) membranes for the treatment of a rabbit alkali-burn lesion. For this purpose, an alkali-burn lesion was induced in 15 rabbits. A week later, clinical events were evaluated and rabbits were divided into five treatment groups: rabbits treated with medical treatment, with a fibrin-PRGF membrane cultured with autologous or heterologous rabbit Limbal Epithelial Progenitor Cells (LEPCs), with a fibrin-PRGF membrane in a Simple Limbal Epithelial Transplantation and with a fibrin-PRGF membrane without cultured LEPCs. After 40 days of follow-up, corneas were subjected to histochemical examination and immunostaining against corneal or conjunctival markers. Seven days after alkali-burn lesion, it was observed that rabbits showed opaque cornea, new blood vessels across the limbus penetrating the cornea and epithelial defects. At the end of the follow-up period, an improvement of the clinical parameters analyzed was observed in transplanted rabbits. However, only rabbits transplanted with cultured LEPCs were positive for corneal markers. Otherwise, rabbits in the other three groups showed positive staining against conjunctival markers. In conclusion, fibrin-PRGF membrane improved the chemically induced lesions. Nonetheless, only fibrin-PRGF membranes cultured with rabbit LEPCs were able to restore the corneal surface.

Platelet-Rich Plasma Applications for Achilles Tendon Repair: A Bridge between Biology and Surgery.

Achilles tendon ruptures are very common tendon ruptures and their incidence is increasing in modern society, resulting in work incapacity and months off sport, which generate a need for accelerated and successful therapeutic repair strategy. Platelet-rich plasma (PRP) is emerging as adjuvant human blood-derived constructs to assist Achilles tendon rupture treatment. However, myriad PRP preparation methods in conjunction with poor standardization in the modalities of their applications impinge on the consistent effectiveness of clinical and structural outcomes regarding their therapeutic efficacy. The purpose of this review is to provide some light on the application of PRP for Achilles tendon ruptures. PRP has many characteristics that make it an attractive treatment. Elements such as the inclusion of leukocytes and erythrocytes within PRP, the absence of activation and activation ex vivo or in vivo, the modality of application, and the adjustment of PRP pH can influence the biology of the applied product and result in misleading therapeutic conclusions. The weakest points in demonstrating their consistent effectiveness are primarily the result of myriad PRP preparation methods and the poor standardization of modalities for their application. Selecting the right biological scaffold and applying it correctly to restitutio ad integrum of ruptured Achilles tendons remains a daunting and complex task.

Anti-inflammatory effect of different PRGF formulations on cutaneous surface.

Cutaneous autoimmune and inflammatory diseases are a major burden of global disease and many lack effective treatments that can derive in different dermatoses like atopic dermatitis. Despite the increase prevalence and the high health-care costs worldwide, the heterogeniety and multifactoriality of these diseases mean that effective treatment options are scarce. Plasma rich in growth factors (PRGF) technology could be an alternative approach that may help in the management of this cutaneous condition. The aim of this study was to assess the effect of two different PRGF formulations (just activated and autologous topical serum (ATS)) for the management of skin inflammation. Additionally, ATS was assessed over two patients suffering from radiotherapy induced dermatitis. Human organotypic skin explant cultures (hOSECs) were used as human skin models. To induce atopic dermatitis-like conditions, skin explants were treated with both interleukin-4 (IL-4) and interleukin-13 (IL-13). PRGF and ATS were intradermally and topically applied, respectively. Metabolic activity, reactive oxigen species (ROS), necrosis and inflammatory cytokine production were determined. Both PRGF formulations increased tissue viability and significantly reduced the excessive free radical accumulation and the cutaneous cytokine production such as TNF-α and IL-1ß. Case reports showed a positive response after ATS treatment in terms of skin quality improvement, local erythema decrease and burning and itching amelioration. The oedema, swelling and desquamation caused by radiation induced dermatitis was also reduced and the patients referred ceased pruritus and pain. This preliminary study suggests that PRGF might aid in the management of inflammatory skin conditions.