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INTRODUCTION: The development of wound dressing materials that combine healing properties, ability to self-repair the material damages, skin-friendly adhesive nature, and competent mechanical properties have surpassing functional importance in healthcare. Due to their specificity, hydrogels have been recognized as a new gateway in biological materials to treat dysfunctional tissues. The design and creation of injectable hydrogel-based scaffolds have extensively progressed in recent years to improve their therapeutic efficacy and to pave the way for their easy minimally invasive administration. Hence, injectable hydrogel biomaterials have been prepared to eventually translate into minimally invasive therapy and pose a lasting effect on regenerative medicine.AREAS COVERED: This review highlights the recent development of adhesive and injectable hydrogels that have applications in wound healing and wound dressing. Such hydrogel materials are not only expected to improve therapeutic outcomes but also to facilitate the easy surgical process in both wound healing and dressing.EXPERT OPINION: Wound healing seems to be an appealing approach for treating countless life-threatening disorders. With the average increase of life expectancy in human societies, an increase in demand for injectable skin replacements and drug delivery carriers for chronic wound healing is expected.

To evaluate the safety and efficacy of the surgical use of autologous plasma rich in growth factors fibrin membrane (mPRGF) in improving corneal wound healing and regeneration in a variety of complex ocular surface defects. Chart review on 15 eyes of 14 included patients undergoing ocular surface intervention using intraoperative mPRGF at the Bascom Palmer Eye Institute and at the Instituto Oftalmologico Fernandez-Vega was performed. Patients were grouped based on type of intervention or condition (penetrating keratoplasty, superficial keratectomy, neurotrophic or persistent corneal ulcers, and corneal perforation). Patients were followed for an average of 11 ± 5 months. Main outcomes measured were mPRGF dissolving time, best-corrected visual acuity, and evidence of any persistent epithelial defects, rejections, or complications. All 15 eyes underwent successful placement of mPRGF. Average dissolving time for fibrin membrane was 21 ± 3 days. mPRGF resulted in total healing of the corneal defects in 13/15 (86.7%) of the treated eyes and partial healing in 2/15 (13.3%) eyes in which persistent epithelial defects were noted on follow-up. Visual acuity improvement was seen in 9/15 (60%) of the cases. The use of autologous mPRGF in the healing and regeneration of the ocular surface is a secure and efficacious surgical option. Our data demonstrate that PRGF fibrin membrane should be contemplated as an important tool to optimize ocular surface regeneration in complex cases.

Irregular hemodynamics affects the progression of various vascular diseases, such atherosclerosis or aneurysms. Despite the extensive hemodynamics studies on animal models, the inter-species differences between humans and animals hamper the translation of such findings. Recent advances in vascular tissue engineering and the suitability of in vitro models for interim analysis have increased the use of in vitro human vascular tissue models. Although the effect of flow on endothelial cell (EC) pathophysiology and EC-flow interactions have been vastly studied in two-dimensional systems, they cannot be used to understand the effect of other micro- and macro-environmental parameters associated with vessel wall diseases. To generate an ideal in vitro model of the vascular system, essential criteria should be included: 1) the presence of smooth muscle cells or perivascular cells underneath an EC monolayer, 2) an elastic mechanical response of tissue to pulsatile flow pressure, 3) flow conditions that accurately mimic the hemodynamics of diseases, and 4) geometrical features required for pathophysiological flow. In this paper, we review currently available in vitro models that include flow dynamics and discuss studies that have tried to address the criteria mentioned above. Finally, we critically review in vitro fluidic models of atherosclerosis, aneurysm, and thrombosis.

Purpose The objective was to evaluate the clinical results obtained from the use of immunosafe plasma rich in growth factors (isPRGF) in the treatment of patients with cicatrizing conjunctivitis (CC) who had not responded to the usual therapy. Patients and methods This is a retrospective study that included patients diagnosed with CC, in whom isPRGF was used in different phases (I: eye drops; II: eye drops and injectable; III: eye drops, injectable and surgical treatment) to achieve control of the inflammation. As a clinical follow-up of the patients, the better corrected visual acuity (BCVA), degree of inflammation (measured from 1 to 4), the severity of the CC, Schirmer I test, IOP and TBUT were analyzed. The adverse events were also evaluated. Results Ten eyes (6 patients) were evaluated, 50% corresponded to Stevens-Johnson Syndrome and 50% to ocular mucous membrane pemphigoid. The mean age was 59.7 ± 16.5 (39-80) years, and 50% were women. Fifty per cent of the cases were initially considered severe CC, and 10% of the cases (one eye of one patient) were considered severe CC at the end of the treatment (p = 0.046). The initial degree of inflammation was 2 in 4 eyes, 3 in two eyes, and 4 in 4 eyes, and final inflammation degree was 1 in all cases (p = 0.004). Twenty per cent of the cases achieved stability in Phase I of the treatment with immunosafe PRGF, 70% with both Phases I and II, and only one case underwent Phase III to achieve stability. The IOP improved significantly (p = 0.027) though the BCVA, TBUT and Schirmer I test showed no significant changes. The follow-up time was 23.1 ± 6.7 (13.6-30.3) months. No adverse effects were reported. Conclusion Treatment with PRGF technology in its injectable and topical immunosafe formulations may be a novel alternative for the treatment of patients with CC, given its complement activity modulating effect, as well as its anti-inflammatory, antifibrotic and regenerative properties.

Introduction: The use of blood derivatives and especially Plasma rich in growth factors (PRGF), for regenerative purposes has been a common trend along the last decades in the field of oral surgery, dermatology, orthopedics, and more recently in ophthalmology.Areas covered: PRGF is a type of platelet-rich plasma that is being explored for the treatment of ocular injuries. The present review article highlights 50 ophthalmology-related publications about the application of PRGF in the treatment of acute and chronic pathologies in ophthalmology as well as most relevant challenges and future prospects.Expert opinion: PRGF technology provides a wide range of formulations that can be used therapeutically in many different acute and chronic ocular pathologies. In addition to eye drops enriched with autologous growth factors, PRGF enables the preparation of both immunologically safe and fibrin-based formulations. Recent advances in the field have promoted PRGF storage for 12 months under freezing conditions, its daily use for 7 days at room temperature and the freeze-dried formulation. The thermally treated immunosafe formulation has shown promising clinical results for the treatment of several diseases such as Sjogren syndrome, graft versus host disease or cicatrizing conjunctivitis. In addition, several fibrin formulations have been preclinically evaluated and clinically incorporated as an adjuvant to ocular surface or glaucoma surgeries, dermal fat graft procedures, limbal stem cell expansion and retinal surgeries. The present review explores the latest scientific and clinical data, current challenges, and main prospects of this technology for the treatment of several ocular injuries.

Tobacco is the leading cause of preventable mortality. The use of mobile phones has grown exponentially, becoming a powerful tool to be used in health care.In order to assess the effectiveness of mobile phones to quit smoking, we have carried out a systematic review and meta-analysis of randomized clinical trials evaluating interventions based on mobile applications for smartphones, that were not a smaller version of the same application, against other types of therapy. To address this, a bibliographic search was carried out in MEDLINE, EMBASE and COCHRANE LIBRARY. To obtain the combined effect, the relative risk and the 95% confidence interval were used. A heterogeneity and sensitivity analysis were also conducted.A total of nine studies were identified, but five were excluded. Qualitative review was performed with four selected studies, but quantitative analysis was carried out for only three, given the impossibility of calculating the RR in one of the studies. After combining the results, an RR of 0.901 (95% CI: 0.57-1.423) was calculated comparing the effectiveness of mobile applications versus others type of interventions. This measure was robust, as shown by the sensitivity analysis.According to the results, it cannot be concluded that apps are effective for quitting tobacco. There are very few clinical trials published evaluating the effectiveness of mobile applications compared to other alternatives. Several clinical trials are still in progress, therefore their results have not been included in the present meta-analysis.

Background Smoking in one of the most serious public health problems. It is well known that it constitutes a major risk factor for chronic diseases and the leading cause of preventable death worldwide. Due to high prevalence of smokers, new cost-effective strategies seeking to increase smoking cessation rates are needed. Methods We performed a Markov model-based cost-effectiveness analysis comparing two treatments: health advice provided by general practitioners and nurses in primary care, and health advice reinforced by sending motivational text messages to smokers’ mobile phones. A Markov model was used in which smokers transitioned between three mutually exclusive health states (smoker, former smoker and dead) after 6-month cycles. We calculated the cost-effectiveness ratio associated with the sending of motivational messages. Health care and society perspectives (separately) was adopted. Costs taken into account were direct health care costs and direct health care cost and costs for lost productivity, respectively. Additionally, deterministic sensitivity analysis was performed modifying the probability of smoking cessation with each option. Results Sending of text messages as a tool to support health advice was found to be cost-effective as it was associated with increases in costs of €7.4 and €1,327 per QALY gained (ICUR) for men and women respectively from a healthcare perspective, significantly far from the published cost-effectiveness threshold. From a societal perspective, the combined programmed was dominant. Conclusions Sending text messages is a cost-effective approach. These findings support the implantation of the combined program across primary care health centres.

Introduction: Tobacco is the leading cause of preventable mortality. The use of mobile phones has grown exponentially, becoming a powerful tool to be used in health care. Methods: In order to assess the effectiveness of mobile phones to quit smoking, we have carried out a systematic review and meta-analysis of randomized clinical trials evaluating interventions based on mobile applications for smartphones, that were not a smaller version of the same application, against other types of therapy. To address this, a bibliographic search was carried out in MEDLINE, EMBASE and COCHRANE LIBRARY. To obtain the combined effect, the relative risk and the 95% confidence interval were used. A heterogeneity and sensitivity analysis were also conducted. Results: A total of nine studies were identified, but five were excluded. Qualitative review was performed with four selected studies, but quantitative analysis was carried out for only three, given the impossibility of calculating the RR in one of the studies. After combining the results, an RR of 0.901 (95% CI: 0.57-1.423) was calculated comparing the effectiveness of mobile applications versus others type of interventions. This measure was robust, as shown by the sensitivity analysis. Conclusions: According to the results, it cannot be concluded that apps are effective for quitting tobacco. There are very few clinical trials published evaluating the effectiveness of mobile applications compared to other alternatives. Several clinical trials are still in progress, therefore their results have not been included in the present meta-analysis.

In recent years, cell microencapsulation technology has advanced, mainly driven by recent developments in the use of stem cells or the optimization of biomaterials. Old challenges have been addressed from new perspectives, and systems developed and improved for decades are now being transferred to the market by novel start-ups and consolidated companies. These products are mainly intended for the treatment of diabetes mellitus (DM), but also cancer, central nervous system (CNS) disorders or lysosomal diseases, among others. In this review, we analyze the results obtained in clinical trials to date and define the global key players that will lead the cell microencapsulation market to bring this technology to the clinic in the future.

Evidences of infectious pathogens in Alzheimer's disease (AD) brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary lactoferrin (Lf) levels, one of the major antimicrobial proteins, in AD patients. To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-β (Aβ) load using amyloid-Positron-Emission Tomography (PET) neuroimaging, in two different cross-sectional cohorts including patients with different neurodegenerative disorders. The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0•95 (0•911-0•992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET+) versus healthy group, and 0•97 (0•924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0•93 (0•876-0•989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from FTD with over 87% sensitivity and 91% specificity. Salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker. Instituto de Salud Carlos III (FIS15/00780, FIS18/00118), FEDER, Comunidad de Madrid (S2017/BMD-3700; NEUROMETAB-CM), and CIBERNED (PI2016/01) to E.C.; Spanish Ministry of Economy and Competitiveness (SAF2017-85310-R) to J.L.C., and (PSI2017-85311-P) to M.A.; International Centre on ageing CENIE-POCTEP (0348_CIE_6_E) to M.A.; Instituto de Salud Carlos III (PIE16/00021, PI17/01799), to H.B. This study was supported by Dr. Carro grants from Instituto de Salud Carlos III (FIS15/00780, FIS18/00118), FEDER, Comunidad de Madrid (S2017/BMD-3700; NEUROMETAB-CM), and CIBERNED(PI2016/01). This study was also supported by research grants fromthe Spanish Ministry of Economy and Competitiveness (SAF2017-85310-R to Dr. Cantero, PSI2017-85311-P to Dr. Atienza); International Centre on ageing CENIE-POCTEP (0348_CIE_6_E to Dr. Atienza);and CIBERNED (CB06/05/1111 to Dr. Cantero). Dr. Bueno receives research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021, PI17/01799). The H2H-Spain Study was supported in Spain by grant PIE16/00021 from Instituto Carlos III, Ministry of Science, Innovation and Universities, and additional funds from the Centro Nacional de Investigaciones Cardiovasculares (CNIC). The CNIC is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Centre of Excellence (SEV-2015-0505). Sí

Preoccupation about potential deleterious effects of pharmaceuticals in the environment is growing fast. Psychiatric pharmaceuticals have received particular attention because of their increasing use and their potential impacts on many living beings due to their effects on phylogenetically highly conserved neuroendocrine systems. Recent studies that have shown that many pharmaceuticals (including psychotropics) bioaccumulate through the web food have raised this concern into new heights. As professionals working in the field of psychiatry and academia, we believe we are about to enter a new era with regard to pharmacotherapy. We estimate drug pollution will have a major impact on our daily practice in a way we are just starting to imagine. So far, this problem has largely been ignored by healthcare professionals, who are the ones prescribing and dispensing pharmaceuticals. We are convinced that increasing awareness among these professionals will be a key element to effectively fight against drug pollution.

Purpose: To evaluate the efficacy and safety of plasma rich in growth factors eye drops for the treatment of corneal and ocular surface disorders in patients with graft versus host disease. Methods: This retrospective and longitudinal study included graft versus host disease patients with ocular disorders. The resolution of corneal ulcers (area and density staining) was evaluated as primary outcome. Best corrected visual acuity, intraocular pressure, tear film breakup time, Schirmer test, ocular surface disease index, and visual analog score were evaluated as secondary outcomes. All variables were analyzed before and after plasma rich in growth factors treatment. The safety of plasma rich in growth factors treatment was also assessed. Results: Twelve patients (23 eyes) with ocular graft versus host disease were evaluated. Statistically significant improvement in the area (75.7%) and density (73.3%) of the corneal staining, in best corrected visual acuity (74.7%), in ocular surface disease index scale (75.4%), visual analog score frequency (81.4%) and visual analog score severity (81.9%), and an increase of 3.8 s in tear film breakup time and 6 mm in Schirmer test was observed after plasma rich in growth factors treatment (p Conclusion: Immunosafe plasma rich in growth factors eye drops for the treatment of patients with ocular graft versus host disease could be safe and effective, showing a high rate of corneal ulcer resolution and dry eye disease control. Plasma rich in growth factors eye drops may help to maintain corneal stability and prevent it against higher ocular complications.

Ronald M Sánchez-Avila,1 Jesus Merayo-Lloves,1 Maria Laura Fernández,1,2 Luis Alberto Rodríguez-Gutiérrez,1 Pedro Pablo Rodríguez-Calvo,1 Andres Fernández-Vega Cueto,1 Francisco Muruzabal,3,4 Gorka Orive,3–6 Eduardo Anitua3,4 1University Institute Fernández-Vega, Ophthalmological Research Foundation, University of Oviedo, Oviedo, Spain; 2Quilmes Eye Center, Buenos Aires, Argentina; 3University Institute for Regenerative Medicine and Oral Implantology (UIRMI), University of the Basque Country, Eduardo Anitua Foundation, Vitoria, Spain; 4Biotechnology Institute (BTI), Vitoria, Spain; 5Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country, Vitoria, Spain; 6Networking Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Vitoria, Spain Purpose: To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) eye drops in patients with glaucoma with secondary ocular surface disorders (OSDs) due to surgeries and topical hypotensive drugs use. Materials and methods: A retrospective case-series study design was used including six patients (eight eyes) diagnosed with glaucoma who received surgical (nonpenetrating deep sclerectomy and/or trabeculectomy) and medical treatments (hypotensive eye drops) to control intraocular pressure (IOP) and who developed secondary OSDs, unresponsive to conventional treatments. Patients were treated with PRGF eye drops (four times a day). Outcome measures were ocular surface disease index (OSDI), best-corrected visual acuity (BCVA, in logarithm of the minimum angle of resolution), visual analog scale (VAS), frequency and severity of symptoms, and IOP. The safety of the treatment was also evaluated. Results: Six patients (seven eyes with open-angle glaucoma and one eye with uveitic glaucoma) treated with PRGF eye drops were evaluated. Mean age was 71 years (SD=7.2, range 58–79 years). Five were female and one was male. The mean treatment time was 21.8 weeks (SD=9.0, range 12–36 weeks). The mean time to reach closure of the corneal ulcer was 14.5 (SD=5.5) weeks. A statistical significant reduction in OSDI scale (50.6%), VAS frequency (53.1%), VAS severity (42.0%), and a 41.8% improvement in BCVA were observed (p

Purpose: To evaluate the potential role of the autologous PRGF (plasma rich in growth factors) fibrin membrane in tissue regeneration after glaucoma filtering surgery. Materials and Methods: Ten patients with medically uncontrolled primary open-angle glaucoma underwent nonpenetrating deep sclerectomy and were treated with PRGF fibrin membrane as adjuvant. Intraocular pressure reduction was the primary outcome. This variable was measured preoperatively and also at each follow-up visit. Secondary outcomes included the number of antiglaucoma medications, anterior segment optical coherence tomography bleb examination, photographic bleb evaluation, and subjective clinical symptomatology evaluation. Results: The surgical technique showed a significant reduction (p < 0.05) in intraocular pressure in relation to preoperative values at each time of the study, decreasing from 23.3 ± 6.4 to 15.2 ± 4.6 mm Hg at 2 years. Furthermore, the number of antiglaucoma medications consumed showed a significant reduction at the end point of the study compared with the preoperative situation. Optical coherence tomography and photographic filtering bleb variables experienced a progressive reduction during the follow-up. Subjective symptoms showed a reduction from 8.3 ± 4.5 to 4.2 ± 5.3 at 2 years. Conclusions: PRGF-Endoret treatment could promote ocular surface regeneration after glaucoma surgery, enhancing the surgery success rates and reducing the need for postoperative medications. It is important to highlight that this is a preliminary study and some large clinical studies are necessary to verify these results.

As social and health needs are changing, new challenges to develop innovative alternatives arise to address unmet medical needs. Personalized medicine is emerging as a promising and appealing therapeutic option. The use of patient's own plasma and platelets as therapeutics is providing new avenues in the treatment of acute and chronic tissue injuries by promoting tissue repair and regeneration. Plasma and platelet-based therapies mimic the physiological repair process by releasing autologous growth factors and creating a natural, biodegradable and transient scaffold that acts as transient matrix. This review summarizes the recent advances and challenges in the field of personalized plasma-based medicine and its potential to treat age-related diseases.

Biological therapeutic therapies are gaining the attention of scientists and medical doctors. Accumulating evidence suggests that blood-derived autologous therapies are safe and effective treatments for skin repair and wound healing. The fibrin network formed after plasmatic activation and the autologous growth factors released when platelets degranulate constitute a real biological medicine that has been shown to promote cell recruitment, stimulate new blood vessel formation, reduce inflammation as well as protect from local infections. This perspective highlights recent basic and clinical results published on blood-derived autologous therapies in the field of regenerative dermatology and discusses potential challenges and future prospects.

Despite uncertainty about its clinical benefit, ivermectin has been used for COVID 19, even in prophylaxis. The European Medicines Agency (EMA) has advised against its use for the prevention or treatment of COVID-19 outside randomised clinical trials. Although the potential negative environmental effects of ivermectin have been widely recognised when used in veterinary medicine, scarce attention has been devoted to the potential ecotoxicological impact of human use. We believe is time to include One Health's philosophy in our daily practice. In the specific case of ivermectin & COVID 19, environmental aspects should also be on the table.

Introduction: In mammals, axons of injured peripheral nerves (PNI) can and do regenerate, but often the functional recovery is incomplete or suboptimal. In recent years, in vivo tissue engineering approaches through molecular intervention and scaffolding are offering promising outcomes. Evidence is accumulating in both preclinical and clinical settings indicating that Platelet-rich plasma (PRP) and fibrin scaffolds obtained from this technology hold an important adjuvant therapeutic potential.Areas covered: This review addresses current molecular and cellular data in intrinsic nerve repair processes and describes different strategies to harness and enhance these processes by using biochemical and biomechanical cues. It focuses on autologous fibrin, plasma and platelet-derived growth factors as filler or scaffolds that can synergize with the gold standard therapy and other nerve guidance conduits.Expert opinion: PRP is applied as a filler of nerve conduits or vein-muscle grafts across nerve gaps po...

Background: Optimal skin repair has been a desired goal for many researchers. Recently, plasma rich in growth factors (PRGF) has gained importance in dermatology proving it is beneficial effects in wound healing and cutaneous regeneration. Objective: The anti-fibrotic, pro-contractile and photo-protective effect of PRGF on dermal fibroblasts and 3D skin models has been evaluated. Method: The effect against TGFβ1 induced myofibroblast differentiation was tested. Cell contractile activity over collagen gel matrices was analyzed and the effect against UV derived photo-oxidative stress was assessed. The effectiveness of PRGF obtained from young aged and middle aged donors was compared. Furthermore, 3D organotypic skin explants were used as human skin models with the aim of analyzing ex vivo cutaneous preventive and regenerative photo-protection after UV exposure. Results: TGFβ1 induced myofibroblast levels decreased significantly after treatment with PRGF while the contractile activity increased compared to the control group. After UV irradiation, cell survival was promoted while apoptotic and ROS levels were noticeably reduced. Photo-exposed 3D explants showed higher levels of metabolic activity and lower levels of necrosis, cell damage, irritation and ROS formation when treated with PRGF. The histological integrity and connective tissue fibers showed lower signals of photodamage among PRGF injected skin models. No significant differences for the assessed biological outcomes were observed when PRGF obtained from young aged and middle aged donors were compared. Conclusion: These findings suggest that this autologous approach might be useful for antifibrotic wound healing and provide an effective protection against sun derived photo-oxidative stress regardless the age of the patient.

Healing process might be considered as a byproduct of the mechanisms underlying the biological defense system consisting of hemostasis and clotting, the innate immune system, and fibrogenesis. But there is no biological process that does not potentially entail high costs through trade-offs with other life-history parameters and that might be seen as collateral damage. Depending on the balance among the robust and flexible modular defense system, which will be deployed in many different arrays, the structural outcome of the healing process will not resolve with a unitary outcome. Drawing on the regenerative potential of platelets, plasma biomolecules and fibrin matrix, several systems of producing autologous platelets-and plasma derived products (APPDPs) have been developed and aimed at enhancing the natural in vivo tissue regenerative capacity of damaged tissues. Despite the care with which the medical staff elaborate and apply autologous platelets-and plasma derived products, some pitfalls arise regarding the composition of autologous plasma-and platelet derived products, the modalities of their application, and the in vitro versus in vivo evaluations, all of which can deeply influence tissue healing - a process which is already unpredictable, without a unitary mechanism that might be deployed in many different structural and functional arrays which culminate in the tissue repair. A biological approach to the application of autologous platelets-and plasma derived products is crucial to obtaining optimum functional healing outcomes in addition to avoiding poor clinical results and reaching misleading conclusions.

Androgenetic alopecia (AGA) is a common hair disorder. Finasteride and minoxidil have been approved by the Food and Drug Administration (FDA) for the treatment of AGA. However, some side effects have been related to the intake of these drugs. Recently, plasma rich in growth factors has emerged as a safe alternative for the management of pattern hair loss. The purposes of the present study are to evaluate and compare the efficacy and safety of plasma rich in growth factors (PRGFs) versus topical minoxidil treatment in AGA-affected patients. Following a retrospective case control design, 379 patients treated with either PRGF or minoxidil were included in this study. Diagnostic trichograms at baseline and 4 months after treatment were performed with the aim of analyzing the anagen/telogen hair change improvement. PRGF-treated patients showed higher anagen hair increase improvement compared to minoxidil-treated ones (6.9 ± 0.4 and 4.6 ± 0.5 %, respectively) (p

Purpose: To compare the clinical and histological outcomes after intrastromal corneal ring segment (ICRS) implantation with and without plasma rich in growth factors (PRGF) in an experimental animal model. Materials and Methods: First, the toxicity of PRGF was tested in hen’s keratocyte cultures. Then, an animal model with 18 hens was randomly divided into 2 groups. In the first group, one ICRS was implanted in each eye (ICRS group). In the second group, the ICRS was firstly immersed 30 min in PRGF-Endoret solution, then implanted and, finally, PRGF-Endoret was inoculated into the channel (PRGF-ICRS group). Animals of each group were also separated into 3 groups regarding the time they were sacrificed, and corneal tissue was fixed for histological analysis at 2, 7 and 30 days. Cell death was detected by terminal uridine nick end labelling (TUNEL) assay. Proliferation was labelled by 5-bromo-2-deoxyuridine (BrdU) incorporation and myofibroblast differentiation by alpha-smooth muscle actin (αSMA) immunodetection. Clinical examination, analyzing epithelial wound closure, deposits and stromal haze, was carried out at the different study times. Results: No toxic effect was observed by PRGF in hen stromal cell cultures. Clinically, in PRGF-ICRS corneas at 7 days, there were more deposits with higher intensity than in ICRS group. Histologically, at day 2 there was less epithelial damage over the segment in the PRGF-ICRS group, corneal oedema around the segment disappeared earlier and, at day 7, there was also double the number of cells around the segment than in the ICRS group displaying different morphologies. The number of TUNEL-positive cells was statistically higher in the PRGF-ICRS group at 7 and 30 days, and the number of BrdU-positive cells was statistically higher at all analyzed times. However, there were no differences in the number of αSMA-positive cells at 30 days between both groups. Conclusions: The ICRS immersion in PRGF-Endoret prior and after to its corneal implantation, in an experimental animal model, enhances clinical deposits and histological cell turnover without increasing myofibroblast differentiation reducing stromal wound-healing time after surgery.

Osteoarthritis (OA) is a progressive joint disease that compromises the structural integrity of cartilage tissue. Conventional treatments based on medication or surgery are nowadays inefficient and cell-based therapy has emerged as one of the most promising methods for cartilage regeneration. The first therapy developed for cartilage defects was autologous chondrocyte implantation, but in the last few decades stem cells (SCs) from different sources have been proposed as a possible alternative for OA.SC sources and available delivery procedures (scaffolds/hydrogels) are presented, along with the main issues arisen in this regard. Thereafter, preclinical and clinical trials performed in recent years are reviewed in order to take a glance toward the potential benefits that such therapies could deliver to the patients.SCs have proven their potential and safety for OA treatment. Nevertheless, there are still many questions to be resolved before their widespread used in clinical practice, such as the treatment mechanism, the best cell source, the most appropriate processing method, the most effective dose and delivery procedure, and their efficacy. In this sense, long-term follow-up and larger randomized controlled trials utilizing standardized and established outcome scores are mandatory to make objective conclusions.

To evaluate the safety and efficacy of the surgical use of plasma rich in growth factors fibrin membrane (mPRGF) in different ocular surface pathologies.Fifteen patients with different corneal and conjunctival diseases were included in the study. Patients were grouped according to the use of mPRGF as graft (corneal and/or conjunctival) or dressing; they were also grouped according to the surgical subgroup of intervention (persistent corneal ulcer [PCU], keratoplasty, superficial keratectomy, corneal perforation, and pterygium). Best corrected visual acuity, intraocular pressure (IOP), inflammation control time (ICT), mPRGF AT (PRGF membrane absorption time), and the healing time of the epithelial defect (HTED) were evaluated throughout the clinical follow-up time. Safety assessment was also performed reporting all adverse events.mPRGF showed a total closure of the defect in 13 of 15 patients (86.7%) and a partial closure in 2 patients (13.3%). The mean follow-up time was 11.14.2 (4.8-22.8) months, the mean ICT was 2.5 +/- 1.1 (1.0-4.0) months, the mean mPRGF AT was 12.4 +/- 2.0 (10.0-16.0) days, and for the global HTED the mean was 2.9 +/- 1.2 (1-4.8) months. Results showed an improvement in BCVA in all patients, with an overall improvement of 2.9 in Vision Lines. The BCVA significantly improved (P.05) throughout the clinical follow-up time. No adverse events were reported after mPRGF use.The mPRGF is effective and safe as coadjuvant treatment in surgeries related with ocular surface disorders, being an alternative to the use of amniotic membrane. The mPRGF accelerates tissue regeneration after ocular surface surgery thus minimizing inflammation and fibrosis. This study received funding from the Ministry of Economy and Competitiveness of the Spanish Government, within the project denominated SURFEYE (reference RTC-2014-2375-1).

Encapsulating, or immunoisolating, insulin-secreting cells within implantable, semipermeable membranes is an emerging treatment for type 1 diabetes. This approach can eliminate the need for immunosuppressive drug treatments to prevent transplant rejection and overcome the shortage of donor tissues by utilizing cells derived from allogeneic or xenogeneic sources. Encapsulation device designs are being optimized alongside the development of clinically viable, replenishable, insulin-producing stem cells, for the first time creating the possibility of widespread therapeutic use of this technology. Here, we highlight the status of the most advanced and widely explored implementations of cell encapsulation with an eye toward translating the potential of this technological approach to medical reality.

Purpose: Preliminary information about the safety and efficacy of plasma rich in growth factors (PRGF) eyedrops in the treatment of refractory cases of diverse ocular surface disorders (OSDs) is presented here. Material and Methods: This retrospective cohort study included cases with OSDs refractory to previous treatment with conventional treatments or autologous serum or cyclosporine, and treated with PRGF eyedrops. The signs and symptoms of ocular surface disorders [using the ocular surface disease index (OSDI), best-corrected visual acuity (BCVA), visual analog scale (VAS) frequency and VAS severity] were evaluated before and after treatment with PRGF. A safety assessment was also performed reporting all adverse events or complications. Results: Forty-one patients with a total of 80 treated eyes were evaluated. Statistically significant reductions in the OSDI scale (39.27%), VAS frequency (38.9%) and VAS severity (40.3%), and a significant improvement in BCVA (54.86%) were all observed (p < 0.05). The results were stratified according to the identified potential effect modifiers. There were only two adverse events (eye redness and eyelid inflammation), which were reported as mild and resolved in a few days. Conclusions: PRGF eyedrops could be a safe and effective treatment option for refractory cases of OSDs. When treating patients the possible influence on the results of some clinical variables must be taken into account.

The purpose of this study is to describe the conservative treatment of severe vertical bone atrophy by combining the insertion of extra-short implants and implant-guided bone augmentation. For that, a low-speed drilling protocol was selected to facilitate the collection of bone particles and to maintain graft osteogenic properties. Extra-short implants were incompletely inserted because of the severe atrophy, and the denuded implant surface was covered by autologous bone particles held together by the adhesive properties of plasma rich in growth factors. The surgical site was then covered with resorbable fibrin membrane, and the flap was repositioned and sutured. Eight patients with a mean residual bone height of 4.19 ± 0.97 mm were treated according to the described treatment protocol. The distance between the implant shoulder and the bony crest was 1.77 ± 0.18, 2.16 ± 0.23, and 1.97 ± 0.26 mm at the mesial, central, and distal aspects, respectively. Vertical bone augmentation resulted in the coverage of 85% of exposed surface by stimulating 1.6 ± 0.5 mm of supra-alveolar bone growth. All 10 extra-short implants placed were successfully osseointegrated. After a mean of 5 ± 1.6 months, provisional screw-retained prostheses were placed. Within the limitations of this study, we conclude that the minimally invasive approach described may successfully rehabilitate extreme vertical bone atrophy in the posterior mandible.

Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is a common problem in patients undergoing long-term administration of highly potent nitrogen-containing bisphosphonates (N-BPs). This pathology occurs via bone and soft tissue mechanism. Zoledronic acid (ZA) is the most potent intravenous N-BP used to prevent bone loss in patients with bone dysfunction. The objective of this in vitro study was to evaluate the role of different ZA concentrations on the cells from human oral cavity, as well as the potential of plasma rich in growth factors (PRGF) to overcome the negative effects of this BP. Primary human gingival fibroblasts and primary human alveolar osteoblasts were used. Cell proliferation was evaluated by means of a fluorescence-based method. A colorimetric assay to detect DNA fragmentation undergoing apoptosis was used to determine cell death, and the expression of both NF-κB and pNF-κB were quantified by Western blot analysis. ZA had a cytotoxic effect on both human gingival fibroblasts and human alveolar osteoblasts. This BP inhibits cell proliferation, stimulates apoptosis, and induces inflammation. However, the addition of PRGF suppresses all these negative effects of the ZA. PRGF shows a cytoprotective role against the negative effects of ZA on primary oral cells. At present, there is no definitive treatment for bisphosphonates-related osteonecrosis of the jaw (BRONJ), being mainly palliatives. Our results revealed that PRGF has a cytoprotective role in cells exposed to zoledronic acid, thus providing a reliable adjunctive therapy for the treatment of BRONJ pathology.

Androgenetic alopecia (AGA) is a common hair disorder that affects both men and women all over the world. Although it is far from being a life-threatening disease, the psychosocial impact of AGA can provoke stress and a significant decrease in life quality. The objective of this retrospective study is to investigate the safety and efficacy of autologous plasma rich in growth factors (PRGF) for the treatment of AGA. One hundred patients were included in this study. They followed two intradermal cycles of PRGF every 4 weeks. Macrophotographs and trichograms were performed at baseline and at 4 months after the first treatment in order to evaluate the overall improvement and determine the anagen/telogen hair ratio, respectively. Patients showed an overall increase in hair density. Trichogram analysis showed that anagen hair follicles increased significantly at 6.2 percentage points (p

Purpose: The aim of this study was to evaluate the use of plasma rich in growth factors (PRGF) eye drops in patients with dry eye disease after laser-assisted in situ keratomileusis (LASIK) surgery. Material and Methods: This is a longitudinal, retrospective, comparative, and descriptive study of 77 eyes of 42 patients with dry eye disease following LASIK surgery. This study was designed to evaluate the efficacy of PRGF treatment compared to conventional therapy (control group). Outcome measures including signs and symptoms of dry eye disease were evaluated before and after treatment. The percentage of change before and after treatment for each clinical variable measured was compared between both groups. Results: There were 1–4 treatment cycles with PRGF eye drops (1 cycle = 6 weeks). Results showed a statistically significant improvement in the Ocular Surface Disease Index (38.12%), visual analogue scale scores for frequency (41.89%) and severity (42.47%), and the Schirmer test scores (88.98%) after PRGF treatment (p < 0.05). No adverse events were reported after PRGF treatment. Conclusions: These results suggest that PRGF eye drops are effective for the improvement of dry eye symptoms in patients who underwent LASIK surgery in comparison to the conventional therapy. The treatment with PRGF is an alternative for patients who suffer from postoperative dry eye.

SummaryBackground Hair transplant surgery using follicular unit extraction technique (FUE) is a common surgical procedure for the treatment of severe hair loss. Blood-derived autologous growth factors have also proved to promote hair regeneration in patients with different types of alopecia. Aims The aim of this study was to evaluate the safety and clinical efficacy of plasma rich in growth factors (PRGF) technology as an adjuvant therapy for FUE surgery in hair loss affected patients. Methods The biologic potential of PRGF was firstly in vitro evaluated over follicular germinal matrix and dermal papilla cells. Afterward, fifteen patients were subjected to routine FUE procedure while 15 patients underwent FUE+PRGF therapy. PRGF group included intradermal injections of growth factors and follicular transfer unit (FTU) preservation in an autologous fibrin clot. Postsurgical patient satisfaction and clinical improvement were evaluated, and PRGF or saline-preserved hair grafts were histomorphometrically analyzed. Results Follicular cell proliferation and migration was induced after autologous growth factors treatment. PRGF-preserved FTUs presented higher bioactivity signals and improved integrity of perifollicular structures and extracellular matrix proteins such as collagen and elastic fibers. PRGF not only reduced the postsurgical crust healing and hair fixation period, but also decreased the inflammatory pain and itching sensation. Conclusions This preliminary data demonstrate that PRGF is able to minimize the postsurgical follicle loss and potentiate the performance of grafted hairs. The fibrin clot not only acts as a protective barrier against environmental factors, but also provides a biologically active scaffold that induces resident cell proliferation and maintains an optimal integrity of the grafted hair.

Type I diabetes mellitus is characterised by the destruction of the insulin producing beta cells within the pancreas by the immune system. After the success of Edmonton protocol, islet transplantation has shown to be a promising therapy, but with the Achilles´ heel of the need of using immunosuppressive drugs. Currently, cell encapsulation technology represents a real alternative to protect transplanted islets from the host´s immune attack. Although preliminary in vitro studies with encapsulated cells have been traditionally performed under static conditions in terms of viability and efficiency, these static cultures do not represent a close approach to in vivo environments. We have developed and characterised different alginate-poly-l-lysine-alginate (APA) microcapsules loaded with the insulin producing 1.1B4 cell line. Static in vitro studies confirmed a constant insulin secretion and a boost of the secretion when the medium was enriched with glucose. Nevertheless, these results were not completely reproduced in a dynamic system by APA liquefied microcapsules containing 1.1B4 cells. The dynamic culture setting created by a microfluidic device, allowed the determination of the glucose response in APA liquefied microcapsules, showing that dynamic conditions can mimic better physiological in vivo environments.

Autologous growth factors have proved to promote tissue regeneration in various medical fields. Recent findings suggest that platelet rich plasma may also play an important role in hair follicle restoration. The objective of this study was to evaluate the safety and clinical efficacy of plasma rich in growth factors (PRGFs) for the treatment of androgenetic alopecia (AGA). Five PRGF injections were administered over 19 patients with AGA. Phototrichograms regarding follicle density/diameter and terminal/vellus hair ratio were performed at baseline and after 1 year follow-up period. Consenting participants underwent histologic scalp examination. At the end of the study, overall patient satisfaction and clinical improvement were determined. After PRGF therapy, mean hair density/diameter increased and terminal/vellus hair ratio was also improved. Patients presented epidermal thickness, perifollicular neoangiogenesis, cell proliferation, and terminal/miniaturized hair ratio improvement. Plasma rich in growth factors seemed to reduce the perivascular inflammatory infiltrate, promote the remodeling of dermo-epidermal tissue, and increase bulge stem cell niches. Patients declared an overall positive satisfaction, and a high clinical improvement score was achieved when comparing premacrophotographs and postmacrophotographs. Although randomized clinical trials are needed, this study provides preliminary data supporting the positive therapeutic effect of autologous growth factors on hair follicle regeneration.

Purpose The goal of this study was to systematically review the efficacy and safety of plasma rich in growth factors (PRGF) as a treatment for reducing symptoms in patients with knee osteoarthritis. Methods A comprehensive and systematic literature search was conducted for PRGF treatment of knee osteoarthritis following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. All the studies had to include a PRGF group and a control group. Pre- and post-treatment measures of joint pain, reduced function, and stiffness were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index, Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee score, Lequesne index, or number of Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI) responders, with a follow-up period of at least 4 weeks. An assessment of both the quality and risk of bias of the studies was conducted. Results The literature search yielded 91 citations, but only 5 were eligible publications that met the inclusion criteria (2 randomized controlled trials, 2 prospective studies, and 1 retrospective analysis). Two studies were rated as having a low risk of bias whereas 3 had a high risk. In both randomized controlled trials, it was observed that after 6 months of treatment, the number of patients with a pain reduction of more than 50% was significantly higher in the PRGF group. In 2 other studies, the patients treated with PRGF showed a significant pain reduction compared with the control group. The remaining variables (Western Ontario and McMaster Universities Osteoarthritis Index scale for pain, function, and stiffness; Lequesne index; Knee Injury and Osteoarthritis Outcome Score scale; and number of OMERACT-OARSI responders) showed a statistically significant superiority of the group treated with PRGF. Conclusions The current clinical evidence suggests that PRGF intra-articular infiltrations in patients with knee osteoarthritis reduce pain and therefore are clinically efficacious in osteoarthritis treatment. Level of Evidence Level III, systematic review of Level I, II, and III studies.

Purpose To report on the outcomes of a new surgical technique for the treatment of severe horizontal bone resorption that impedes the placement of dental implants. Materials and Methods Eleven patients in need of bone augmentation to reconstruct a narrow alveolar ridge were recruited for the present study. Surgical correction of the alveolar width was performed by harvesting an onlay bone graft from the lateral wall of the maxillary sinus and filling the intervening space with plasma rich in growth factors alone or mixed with autologous bone particles. A fibrin membrane was then placed to cover the surgical site before flap closure. Clinical examinations and cone-beam computed tomography were performed to analyze the safety and efficiency of an onlay bone graft from the maxilla in horizontal bone augmentation. Results The present study is the first to describe the lateral wall of the maxillary sinus as a donor site for an onlay bone graft. The healing period was uneventful, with minimal surgical morbidity. No flap exposure occurred, and analysis of the cone-beam computed tomography scans before and after (about 5 months) bone augmentation revealed a total gain of 5.4 mm in alveolar width. This permitted the placement of dental implants to support an implant-borne prosthesis. Conclusions An onlay bone graft from the lateral wall of the maxillary sinus is a useful and safe tool for horizontal bone augmentation with minimal surgical morbidity.

This study evaluated the efficacy of Plasma rich in growth factors (PRGF-Endoret) on the corneal wound healing process after Photorefractive keratectomy (PRK). To address this, blood from three healthy donors was collected, centrifuged and, the whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were collected. The effects of F3 and WP on the proliferation and migration of human corneal epithelial cells (HCE) were analyzed. PRK was performed on C57BL/6 mice. Animals were divided in three treatment groups: Control, F3, and WP. Corneal wound healing and haze formation were evaluated macroscopically. Eyes were collected at 1, 2, 3, and 7 days after surgery, and were processed for histological studies. Immunofluorescence was used to assess cellular proliferation, apoptosis and myofibroblast transformation in the mouse cornea. Results showed a significant increased on proliferation and wound healing after F3 and WP treatment when compared with control group. In vivo studies showed significant reduction on haze formation in mice treated with both PRGF-Endoret formulations (F3 and WP). Histological studies showed an increase of epithelial cell proliferation in corneas of control group, promoting an epithelial hyperplasia. The number of SMA-positive cells (corresponding to myofibroblast differentiation) was significantly lower in the PRGF-Endoret group than in the control group, correlating with the higher transparence results observed macroscopically in both PRGF-Endoret groups. According to this, it can be concluded that PRGF-Endoret accelerates corneal tissue regeneration after PRK, reducing haze formation.

The aim of this meta-analysis was to evaluate the efficacy and safety of two bisphosphonates (alendronate and zoledronate) in the treatment of postmenopausal osteoporosis. The incidence of fractures was considered as primary endpoint. Only randomized trials with a follow-up period of 1 year or more were included in this systematic review and meta-analysis. We excluded studies that included patients with secondary osteoporosis especially in relation to therapy with corticosteroids or other drugs or diseases known to affect bone mineral density. Studies published as subgroup analysis, extension studies, economic evaluations, and comparisons with active control were excluded. The methodological quality of controlled clinical trials that met these inclusion criteria was evaluated. No studies were excluded from analysis due to lack of quality. The risk ratio of hip, vertebral and wrist fractures for alendronate were 0.61 [95% confidence interval (CI) 0.40-0.93], 0.54 (95% CI 0.44-0.66) and 0.65 (95% CI 0.33-1.25), respectively. Zoledronate risk ratio was 0.62 (95% CI 0.46-0.82) and 0.38 (95% CI 0.22-0.67) for hip and vertebral fractures, respectively.

Adipose tissue-derived stem cells (ASCs) have properties of self-renewal, pluripotency and high proliferative capability that make them useful for the treatment of cardiac ventricular function following ischaemic injury. However, their therapeutic use is limited due to the low retention of the cells at the targeted site. To address this issue, we developed semipermeable membrane microcapsules labelled with Endorem (magnetocapsules) that provide mechanical and immunological immune protection to the cells while maintaining internal cell microenvironment. In addition, the particles allow tracking the presence and migration of injected cells in vivo by Magnetic Resonance Imaging (MRI). Results indicate that after 21 days in culture, the cells encapsulated in the magnetocapsules showed similar viabilities than cells encapsulated in conventional microcapsules. MRI confirmed a gradual loss of the intensity of the iron oxide label in the non-encapsulated Endorem labelled cells, while magnetocapsules were detected throughout the study period, suggesting that cell retention in the myocardium is improved when cells are enclosed within the magnetocapsules. To further evaluate treatment's effect on global cardiac function, MRI determination of infarct size and left ventricular ejection fraction (LVEF) was performed. In vivo results showed no statistically significant differences in heart rate and cardiac output between treatment groups. In conclusion, cells enclosed within magnetocapsules have shown suitable viability and have been detected in vivo throughout the study period. Further studies will evaluate whether increasing cell loading with the particles may help to improve the therapeutic results.

The use of allogeneic blood therapies has opened new avenues in several medical fields including ophthalmology.1 Blood-based platelet and plasma products mimic natural tears because of their content in growth factors, cytokines, vitamins and nutrients, which are essential for maintaining the homeostasis of the normal ocular surface tissues.1 Although autologous eye drops are commonly used in the management of ocular disorders, not all patients are candidates as donors due to systemic inflammatory diseases, age, and other types of disorders or comorbidities. In these cases, an allogeneic blood-based product may represent an alternative to manage several ocular surface injuries, such as severe dry eye and persistent corneal epithelial defects.2, 3 The use of allogeneic therapies has major concerns, including hypersensitivity reactions in the recipient, the risk of blood-borne pathogen infection, and the requirement of tests for transfusion- transmissible infections and virus screening in the eye drops. Recently, solvent/detergent virally inactivated blood-based eye drops and the photochemical treatment of the allogeneic formulations have been proposed for virus inactivation.4

To assess the clinical efficacy and safety of a treatment based on one cycle versus two cycles of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) on patients with knee osteoarthritis (OA). Ninety patients with knee OA were included and evaluated. A total of 48 patients received one cycle (OC group) (3 injections on a weekly basis), while 42 patients received two cycles of PRGF-Endoret (TC group) spaced 6 months between them. Patients were evaluated with LEQUESNE and WOMAC scores before treatment and after 48 weeks. Safety assessment was also performed. A significant reduction of all assessed outcome measures was shown for both groups at 48 weeks compared with baseline values (P

To provide preliminary data about efficacy and safety of plasma rich in growth factors (PRGF) eye-drops in neurotrophic keratitis (NK) and to analyze the possible influence of certain variables on treatment outcomes. This retrospective study included patients with stages 2–3 of NK treated with PRGF eye-drops. Primary endpoint was the resolution time of corneal ulcer defect. Outcome measures including percentage of ulcer closure at 4 weeks, Ocular Surface Disease Index (OSDI), Best-Corrected Visual Acuity (BCVA) and Visual Analogue Scale (VAS) were also evaluated before and after treatment with PRGF. The influence of some patients’ clinical variables on results was assessed. Safety assessment was also performed reporting all adverse events. Thirty-eight treated eyes in a total of thirty-one patients were evaluated, of which five cases had no prior response to autologous serum treatment. Most cases (97.4%) achieved the complete resolution of corneal defect/ulcer. Mean resolution time was 11.4 weeks (SD = 13.7). A statistical significant (p

Objectives To evaluate the biological outcomes of plasma rich in growth factors (PRGF) on human endometrial fibroblasts in culture. Study design PRGF was obtained from three healthy donors and human endometrial fibroblasts (HEF) were isolated from endometrial specimens from five healthy women. The effects of PRGF on cell proliferation and migration, secretion of vascular endothelial growth factor (VEGF), procollagen type I and hyaluronic acid (HA) and contractility of isolated and cultured human endometrial fibroblasts (HEF) were analyzed. Statistical analysis was performed in order to compare the effects of PRGF with respect to control situation ( T -test or Mann–Whitney U -test). Results We report a significantly elevated human endometrial fibroblast proliferation and migration after treatment with PRGF. In addition, stimulation of HEF with PRGF induced an increased expression of the angiogenic factor VEGF and favored the endometrial matrix remodeling by the secretion of procollagen type I and HA and endometrial regeneration by elevating the contractility of HEF. These results were obtained for all PRGF donors and each endometrial cell line. Conclusions The myriad of growth factors contained in PRGF promoted HEF proliferation, migration and synthesis of paracrine molecules apart from increasing their contractility potential. These preliminary results suggest that PRGF improves the biological activity of HEF in vitro , enhancing the regulation of several cellular processes implied in endometrial regeneration. This innovative treatment deserves further investigation for its potential in “ in vivo ” endometrial development and especially in human embryo implantation.

Background: Ultraviolet irradiation is able to deeply penetrate into the dermis and alter fibroblast structure and function, leading to a degradation of the dermal extracellular matrix. Objectives: The regenerative effect of plasma rich in growth factors (PRGF) on skin ageing was investigated using UVB photo-stressed human dermal fibroblasts as an in vitro culture model. Method: PRGF was assessed over the main indicative features of ultraviolet B irradiation, including ROS formation, cell viability and death detection, apoptosis/ necrosis analysis and biosynthetic activity measurement. Four different UV irradiation protocols were tested in order to analyze the beneficial effects of PRGF. Results: Ultraviolet irradiation exhibited a dose dependent cytotoxicity and dose of 400mJ/cm2 was selected for subsequent experiments. PRGF increased the cell viability and decreased the cell death comparing to the non-treated group. The apoptosis and necrosis were significantly lower in PRGF treated fibroblasts. ROS production after UV irradiation was significantly reduced in the presence of PRGF. Procollagen type I, hyaluronic acid and TIMP-1 levels were higher in the when treated with PRGF. Conclusion: This preliminary in vitro study suggests that PRGF is able to prevent UVB derived photooxidative stress and to diminish the cell damage caused by ultraviolet irradiation.

Knee osteoarthritis (KOA) is a mechanically induced, cytokine and enzyme-mediated disorder involving all the joint tissue of the knee. Rebuilding a physiological-homeostatic network at the tissue level following knee organ failure, such as in severe KOA, is a daunting task with therapeutic targets encompassing the articular cartilage, synovium and subchondral bone. Intraarticular infiltration of plasma rich in growth factors (PRP) has emerged as a promising symptomatic approach, although it is insufficient to reach the subchondral bone.This review addresses current molecular and cellular data in joint homeostasis and osteoarthritis pathophysiology. In particular, it focuses on changes that subchondral bone undergoes in knee osteoarthritis and evaluates recent observations on the crosstalk among articular cartilage, subchondral bone and synovial membrane. In addition, we review some mechanistic aspects that have been proposed and provide the rationale for using PRP intraosseously in KOA.The knee joint is a paradigm of autonomy and connectedness of its anatomical structures and tissues from which it is made. We propose an innovative approach to the treatment of severe knee osteoarthritis consisting of a combination of intraarticular and intraosseous infiltrations of PRP, which might offer a new therapeutic tool in KOA therapy.

The purpose of this work is to describe and review the technology of plasma rich in growth factors (PRGF), a novel blood derivative product, in the treatment of ocular surface disorders.To demonstrate the importance of this technology in the treatment of ocular pathologies, a thorough review of the preclinical and clinical literature results obtained following use of the different therapeutic formulations of PRGF was carried out. A literature search for applications of PGRF plasma in the ophthalmology field was carried out using the PubMed database.PRGF involves the use of patient's own biologically active proteins, growth factors, and biomaterial scaffolds for therapeutic purposes. This procedural technology is gaining interest in regenerative medicine due to its potential to stimulate and accelerate the tissue healing processes. The versatility and biocompatibility of this technology opens the door to a personalized medicine on ocular tissue regeneration. This review discusses the state of the art of the new treatments and technologies developed to promote ocular surface tissue regeneration. The standardized protocol that has been developed to source eye drops from PRGF technology is also described. The preclinical research, together with the most relevant clinical applications are summarized and discussed.The preliminary results suggest that the use of PRGF to enhance ocular tissue regeneration is safe and efficient.