Delivery Of Platelet-rich Plasma Research Articles

Injectable GelMA Hydrogel Microspheres with Sustained Release of Platelet-Rich Plasma for the Treatment of Thin Endometrium.

Platelet-rich plasma (PRP) intrauterine infusion has been demonstrated to be effective in treating thin endometrium and achieving pregnancy. However, the rapid release of growth factors limits its effectiveness in clinical applications, and thus, multiple intrauterine infusions are often required to achieve therapeutic efficacy. In this study, a GelMA hydrogel microsphere biomaterial is developed using droplet microfluidics to modify the delivery mode of PRP and thus prolong its duration of action. Its biocompatibility is confirmed through both in vivo and in vitro studies. Cell experiments show that PRP-loaded microspheres significantly enhance cell proliferation, migration, and angiogenesis. In vivo experiments show that the effects of PRP-loaded microspheres on repairing the endometrium and restoring fertility in mice could achieve the impact of triple PRP intrauterine infusions. Further mechanistic investigations reveal that PRP could facilitate endometrial repair by regulating the expression of E2Fs, a group of transcription factors. This study demonstrates that hydrogel microspheres could modify the delivery of PRP and prolong its duration of action, enabling endometrial repair and functional reconstruction. This design avoids repeated intrauterine injections of PRP in the clinic, reduces the number of patient visits, and provides a new avenue for clinical treatment of thin endometrium.

BIOFUNCTIONALIZED 3D-BIOPRINTED VASCULAR-LIKE STRUCTURES: AN ADVANCED APPROACH TO PROMOTE ENDOTHELIAL TISSUE REGENERATION

Biofabrication is a popular technique to produce personalized constructs for tissue engineering. In this study we combined laponite (Lap), gellan gum (GG) with platelet-rich plasma (PRP) aiming to enhance the endothelial regeneration through the synergistic effects of their individual properties. Laponite has the ability to form porous three-dimensional networks mimicking the extracellular matrix structure, and PRP delivery of growth factors stimulates the endothelial cell proliferation and migration, offering a composite bioink for cell growth and support. The sustained release of these growth factors from the GG-laponite-PRP composite material over time provides a continuous source of stimulation for the cells, leading to more effective tissue engineering strategies for endothelial tissue regeneration. Four blend compositions comprising 1% w/v GG and 0.5 or 1% w/v Lap and 25% v/v PRP were combined with Wharton jelly mesenchymal stem cells (WJ-MSCs) and bioprinted into vessel-like structures with an inner diameter of 3 mm and a wall thickness of 1 mm. Stress/strain analysis revealed the elastomeric properties of the hydrogels with Young modulus values of 10 MPa. Increasing the Lap concentration led to a non-significant decrease of swelling ratio from 93 to 91%. Live/dead assay revealed cell viability of at least 76%, with the 0.5%Lap-GG viability exceeding 99% on day 21. Gradual increase of glycosaminoglycans accumulation and collagen production indicate promotion of ECM formation. The expression and membranous localization of PECAM-1 from day 7 and the granular intracellular localization of vWF after 2 weeks demonstrate in vitro endothelial functionality. In vivo subcutaneous implantation indicated the absence of any adverse immunological reactions. The results reveal the expression of both vWF and PECAM-1 by WJ-MSCs entrapped in all four construct compositions with significantly higher expression of vWF in the presence of PRP.

Topical ocular administration using thermosensitive chitosan-glycerophosphate-PRP hydrogels for improved ocular bioavailability

PurposeOne of the difficulties in the pharmacy field is the delivery of drugs for the eyes. Topical therapy is one of the most common methods for treating eye diseases. Due to their unique properties, including biocompatibility and suitable degradation, hydrogels are appropriate for biological purposes. Platelet-rich plasma (PRP), as a designated concentration of platelets, is in a smaller volume than the plasma and is considered a rich source of growth factor that has been used in recent years, including applications in eye diseases including corneal wound healing, improvement of dry eye and post-LASIK syndrome. MethodsThe present study was performed to fabricate Chitosan (CS) and glycerophosphate (GP) based hydrogels that are temperature-sensitive for PRP and investigate their effect on ocular stem cells. ResultsCS-GP-based temperature-sensitive hydrogels containing PRP were successfully fabricated using CS and GP. This hydrogel is liquid at ambient temperature and a gel at ocular temperature. Rheology, FTIR, and SEM tests assessed the properties of the hydrogels. The results of the MTT test showed that the hydrogel made with the optimal formulation was not toxic to LSC cell lines. ConclusionsGiven this, CS-GP-based hydrogels can be applied as a biocompatible formulation in ocular medication administration with increased bioavailability at the ocular surface and topical delivery of PRP.

EFFICACY OF ULTRASONIC TRANSDERMAL PLATELET RICH PLASMA ON CHRONIC LOWER LIMB VENOUS ULCER HEALING

The present study was carried-out to examine the impact of Ultrasonic Transdermal Delivery of platelet rich plasma (PRP)on chronic lower limb venous ulcer healing. Design: Randomized controlled trial. Patients and methods: The present work was conducted on sixty patients with chronic lower limb venous ulcers who took-part in this study, they aged from 40 to 60 years. The participants were recruited from Mataria teaching hospital and were randomized into two groups; each group consisted of 30 patients. Group A (Ultrasonic PRP group) received Ultrasonic Transdermal Delivery of autologous PRP twice weekly for a month in addition to medical care and group B (Control group) received medical care in form of antimicrobial dressing, wound care and debridement of ulcers. Saline method was used to measure the ulcer volume. Digital photography/imaging and surface area estimation software (Image J) was used to measure ulcer surface area. Results: After treatment, there was significant decline in wound surface area as well as volume of PRP group in comparison with the control group (p < 0.001). Conclusion: Adding Ultrasonic transdermal delivery of platelets rich plasma to medical treatment of chronic venous ulcer can enhance healing process by reducing surface area and ulcer volume and it is considered a safe, simple, inexpensive and cost effective modality.

Current Status of PRP Manufacturing Requirements & European Regulatory Frameworks: Practical Tools for the Appropriate Implementation of PRP Therapies in Musculoskeletal Regenerative Medicine.

Providing accurate and up-to-date practical tools enabling oversight of platelet-rich plasma (PRP) legislation and of the appropriate standards to be implemented for its manufacture and use in Europe is a demanding task. This is due to rapid medico-technological advancements, slowness and disparity in legislation updates and enforcement between member states, and many reported gray-zone practices, notably for autologous PRP use. The levels of risk associated with blood manipulation processes generally dictate the manufacturing requirements for PRP preparations, which have gradually shifted toward good manufacturing practices (GMP) for standardization and overall quality enhancement. This work firstly outlines Western European and Swiss legislation for PRP products/preparations, providing key simplified information and recommendations for medical doctors seeking to implement this biological-based therapy for safe use in hospital settings, clinics, or private offices. This work secondly shows the importance of PRP-based product manufacturing standardization, which subsequently enables sound clinical evaluation of therapeutic interventions. Although the applicable legal bases provide guidelines for GMP manufacturing infrastructure and basic process design, paramount importance is set on the definition of workflows, technical specifications, and key parameters for PRP preparation and delivery. Overall, the development of simple and robust technologies and processes for PRP preparation is critical for guaranteeing the high therapeutic quality of the intervention, in collaboration with qualified GMP manufacturing platforms. Importantly, this work aims to serve as a practical tool for clinicians based in Western Europe who are willing to appropriately (i.e., administratively and technically) implement autologous PRP treatments in musculoskeletal regenerative medicine workflows, to ensure they make informed and optimal regulatory or process-based decisions.

Nanofiber reinforced alginate hydrogel for leak-proof delivery and higher stress loading in nucleus pulposus

Injectable hydrogels effectively remodel degenerative nucleus pulposus (NP) with a resemblance to the in vivo microenvironment. However, the pressure within the intervertebral disc requires load-bearing implants. The hydrogel must undergo a rapid phase transition upon injection to avoid leakage. In this study, an injectable sodium alginate hydrogel was reinforced with silk fibroin nanofibers with core-shell structures. The nanofiber-embedded hydrogel provided support to adjacent tissues and facilitated cell proliferation. Platelet-rich plasma (PRP) was incorporated into the core-shell nanofibers for sustained release and enhanced NP regeneration. The composite hydrogel exhibited excellent compressive strength and enabled leak-proof delivery of PRP. In rat intervertebral disc degeneration models, radiography and MRI signal intensities were significantly reduced after 8 weeks of injections with the nanofiber-reinforced hydrogel. The biomimetic fiber gel-like structure was constructed in situ, providing mechanical support for NP repair, promoting the reconstruction of the tissue microenvironment, and finally realizing the regeneration of NP.

Platelet-Rich Plasma in Melasma—A Systematic Review

BACKGROUND Melasma is a common relapsing hyperpigmentation disorder, which is often difficult to treat. Platelet-rich plasma (PRP) is a novel modality often used to treat acne scars, androgenic alopecia, chronic wounds, and skin rejuvenation. Recently, it has had a promising role in the treatment of melasma. OBJECTIVE To review the published evidence on the efficacy and safety of PRP in the treatment of melasma. MATERIALS AND METHODS A systematic review was performed. A meta-analysis could not be performed because of methodological differences across studies and data heterogeneity. RESULTS Seven studies were fulfilled and analyzed. Most studies used intradermal injections of PRP and have shown significant improvement in melasma. Microneedling mediated delivery of PRP has been tried in melasma with good results. A single study showed no additional benefit of PRP in patients treated with topical tranexamic acid. Another study showed no benefit of intense pulsed light in patients treated with intradermal PRP. CONCLUSION Platelet-rich plasma inhibits the melanin synthesis through its various components acting through several mechanisms. It demonstrates a moderate grade of recommendation according to the Oxford Center for Evidence-Based Medicine 2011 standards.

Platelet-Rich Plasma: Optimal Use in Surgical Wounds

Activated platelets release a rich broth of growth factors involved in wound healing. One way to deliver activated platelets to wounds is in the form of platelet-rich plasma (PRP) harvested by centrifuging the patient's venous blood after activating the platelets with collagen or calcium chloride and/or autologous thrombin, then delicately removing the supernatant, called platelet-poor plasma (PPP). Platelet-rich plasma is usually injected into the lesion and/or applied topically, then sealed in or over the wound using a moisture-retentive dressing. Platelet-rich plasma (often with PPP) has been applied at different times, depths, and frequencies to chronic and acute wounds using various PRP doses and vehicles to achieve widely differing results. Meta-analyses have reported that PRP improved healing rates of open diabetic foot ulcers and venous ulcers and may reduce pain and surgical site infection (SSI) incidence in open and closed acute surgical wounds. However, inconsistency in study methods and outcome measures limited consistency of pain and SSI results. No consistent effect on healing or deep SSI rates was reported as a result of adding 1 intraoperative dose of PRP in the surgical site before closing elective foot and ankle surgery incisions of 250 patients as compared with 250 similar patients receiving the same procedure without PRP. After decades of research, ideal parameters of PRP delivery and use on each type of wound remain unclear for improving SSI, acute wound pain, and healing outcomes. This installment of the Evidence Corner reviews 2 surgical studies that may provide clues about optimal PRP use. One triple-blind randomized clinical trial (RCT) focused on irrigation of freshly closed carpal ligament surgical incisions with PRP as compared with PPP. Another non-blind RCT explored the effect of injecting PRP into open pilonidal sinus excisions 4 days and 12 days after surgery.

Evaluating the Safety of Intravenous Delivery of Autologous Activated Platelet-rich Plasma

Introduction: Autologous platelet-rich plasma (PRP) has been a growing trend in the field of medicine due to its broad range of application and is considered safe from bloodborne diseases. Furthermore, various studies have tried to optimize the use of autologous PRP through various preparation protocols, including PRP activation. However, most of the studies available have not evaluated the safety for intravenous delivery of PRP, especially autologous activated PRP (aaPRP). Therefore, this study aimed to evaluate the safety of intravenous delivery of aaPRP.Methods: Blood was drawn from each patient and aaPRP was isolated through calcium activation and light irradiation. Each aaPRP was administered intravenously to all patients. Adverse events were documented and analyzed.Results: Six hundred eleven patients participated in this study with a total of 4244 aaPRP therapies. Quality control of autologous aaPRP showed no platelets present after both calcium activation and light irradiation. No adverse events such as allergic reaction, infection, and coagulation problems were observed on all patients over the course of the study.Conclusion: Our results showed that intravenous administration of autologous aaPRP is safe even in patients with various pathological conditions.

Low-fluence laser-facilitated platelet-rich plasma permeation for treating MRSA-infected wound and photoaging of the skin

Platelet-rich plasma (PRP) is rich in cytokines and growth factors and is a novel approach for tissue regeneration. It can be used for skin rejuvenation but the large molecular size of the actives limits its topical application. In this study, low-fluence laser-facilitated PRP was delivered to evaluate its effect on absorption through the skin, infection-induced wound, and photoaging. The PRP permeation enhancement was compared for two ablative lasers: fractional (CO2) laser and fully-ablative (Er:YAG) laser. In the Franz cell experiment, pig skin was treated with lasers with superficial ablation followed by the application of recombinant cytokines, growth factors, or PRP. The transport of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was negligible in intact skin and stratum corneum (SC)-stripped skin. Both lasers significantly elevated skin deposition of IFN-γ and TNF-α from PRP, and fully-ablative laser showed a higher penetration enhancement. A similar tendency was found for vascular endothelial growth factor and epidermal growth factor. Er:YAG laser-exposed skin displayed 1.8- and 3.9-fold higher skin deposition of platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-β1 from PRP, respectively. According to the confocal images, both laser interventions led to an extensive and deep distribution of IFN-γ and PDGF-BB in the skin. In the in vivo methicillin-resistant Staphylococcus aureus (MRSA) infection model, CO2 laser- and Er:YAG laser-assisted PRP delivery reduced bacterial load from 1.8 × 106 to 5.9 × 105 and 1.4 × 104 colony-forming units, respectively. The open wound induced by MRSA was closed by the laser-assisted PRP penetration. In the mouse photoaging model, elastin and collagen deposition were fully restored by combined PRP and full-ablative laser but not by PRP alone and PRP combined with fractional laser. Laser-facilitated PRP delivery even with a low fluence setting can be considered a promising strategy for treating some dermatological disorders.

Effectiveness of Platelet-Rich Plasma in the Prevention of Chlamydia-Induced Hydrosalpinx in a Murine Model.

Chlamydia trachomatis (C. trachomatis) is a major pathogen implicated in the formation of hydrosalpinx in the female reproductive tract. In mice, a related strain of Chlamydia, Chlamydia trachomatis (C. trachomatis) can induce almost 100% bilateral hydrosalpinx. This model was used as a hydrosalpinx induction model to test whether oviduct delivery of platelet-rich plasma (PRP) can attenuate chlamydia induction of hydrosalpinx in a mouse model. Mice were infected intravaginally with Chlamydia muridarum organisms, and 21days after the infection, PRP was instilled into the lumen of one oviduct, and a sham instillation with phosphate buffer solution was performed on the contralateral oviduct. Mice were then sacrificed at designated time points after infection for oviduct pathologic evaluation including incidence, severity, and histopathologic grade of chronic inflammation. Oviduct instillation of PRP was associated with a 36% reduction in the incidence of hydrosalpinx and a 33% reduction in severity compared with sham. The median grade of chronic inflammation on histopathology was significantly lower with PRP instillation compared with sham and control. No differences were observed in vaginal or rectal shedding of C. muridarum between the test group and the control group. In short, the results suggest that oviduct instillation of PRP can significantly reduce the incidence and severity of C. muridarum-induced hydrosalpinx without affecting chlamydial infection courses in CBA/J mice.

CORR Synthesis: What Is the Role of Platelet-rich Plasma Injection in the Treatment of Tendon Disorders?

CORR Synthesis: What Is the Role of Platelet-rich Plasma Injection in the Treatment of Tendon Disorders?

Platelet-rich plasma in alopecia areata: intradermal injection versus topical application with transepidermal delivery via either fractional carbon dioxide laser or microneedling

Alopecia areata (AA) is a common cause of non-scarring alopecia with variable response to treatment. Platelet-rich plasma (PRP) stimulates proliferation and differentiation of stem cells in the hair-follicle bulge via multiple mechanisms. Although beneficial, pain during injection in addition to unequal delivery and coverage is a major drawback of intralesional PRP in alopecia, particularly for extensive lesions and in patients with a low pain threshold. This study evaluates intradermal injection of PRP versus its topical use with enhanced transepidermal delivery through either fractional CO2 laser (FCL) or microneedling in treatment of AA. Sixty AA patients were randomized into three equal groups to receive monthly sessions of either PRP intradermal injection, FCL followed by topical PRP, or microneedling followed by topical PRP for 3 consecutive months. Assessment was done through the Severity of Alopecia Tool (SALT) score and patient satisfaction at the end of sessions (2 weeks after the last session) and after 3 additional months of follow-up. Patients in all groups showed satisfactory results of PRP treatment, with statistically insignificant differences in the degree of improvement among patients of the three groups studied according to the two assessment parameters. Intralesional PRP injection was associated with significantly higher pain scores. PRP is potentially effective and safe for treatment of AA. FCL and microneedling could facilitate topical PRP delivery and considerably decrease pain associated with intradermal injection while preserving PRP efficacy. These methods could be helpful for extensive lesions and in children.

Use of Autologous Blood Components in Lymphedema Treatment: A Systematic Review.

The main benefit of autologous therapies is its easier obtention and relatively lower concerns regarding ethical implications and patient safety. We conducted a systematic review of publications assessing the potential use of blood components (lymphocytes, red blood cells (RBCs), platelet-rich plasma (PRP)) as targeted therapy in the treatment of lymphedema. We hypothesized that blood components could be used as targeted therapy in the lymphedema treatment. We also conducted a comprehensive, systematic review of the published literature on the use of blood components as targeted therapies in the treatment of lymphedema using the PubMed database. Eligibility criteria excluded papers that aimed to investigate the correlation of inflammatory cells and the physio-pathogenesis of lymphedema. s, presentations, reviews, and meta-analyses were also excluded. From the 338 potential papers found in the literature, 11 studies fulfilled the eligibility criteria. Different types of targeted therapies were proposed, but the majority of papers investigated the potential use of lymphocytes (9/11). The use of PRP was investigated in two papers and the use of RBCs in one paper. Interestingly, six out of 11 studies were done on patients with lymphedema, but the most recent was published in 1999. The remaining publications were experimental studies on dogs, rats, or in vitro. The publications demonstrated positive outcomes for the delivery of lymphocytes and PRP in lymphedema treatment. Lymphocyte was the most common blood component investigated. Even though more than half of the papers found were conducted on patients, we noticed a scientific gap of more than 20 years on the topic.

Platelet-rich plasma is a useful therapeutic option in melasma

Background: Melasma is a cosmetically disfiguring disorder of facial pigmentation.Objectives: We evaluated the value of platelet-rich plasma (PRP) in the treatment of melasma using two different delivery techniques: microneedling using dermapen versus microinjections using mesoneedles.Patients and methods: Twenty-three adult Egyptian melasma patients were enrolled. Wood’s light was used to determine the histological type of melasma. Autologous PRP was delivered into the lesional melasma skins through microneedling with dermapen on the right side of the face and intradermal microinjections using mesoneedles on the left side of the face (for each patient). The treatment was done regularly (three sessions, each month). The response to PRP therapy was measured using melasma area and severity index (MASI) and modified melasma area and severity index (mMASI) that were calculated before and after three treatment sessions. Hemi-MASI was used to compare the effectiveness of the two delivery techniques.Results: Following PRP treatment, MASI and mMASI scores decreased significantly from 11.86 ± 5.25 to 6.96 ± 4.82, and from 5.71 ± 2.56 to 2.90 ± 2.05, respectively (p < .000,). A statistically significant decrease was noted in the hemi-MASI score on each side of the face following PRP treatment (p < .000), but there was no significant difference in comparing both sides.Conclusions: Our study provides the first indication about the value of PRP as a useful and new therapeutic option in melasma. Moreover, our study was the first to compare PRP delivery through microneedling versus microinjections.

The use of platelet-rich plasma (PRP) in the treatment of gastrocnemius strains: a retrospective observational study

The aim of the present retrospective observational study was to evaluate the time of functional recovery following a specific combined therapeutic approach characterized by an active exercise therapy carried out immediately after Platelet-rich plasma (PRP) injections for the treatment of the muscular lesion of the distal musculotendinous junction of the gastrocnemius medial head.Medical records of 31 subjects treated with three PRP intra-lesional ultrasound guided injections and 30 patients treated with the standard therapeutic approach (control group) were analyzed. Both groups followed the same rehabilitation therapy. Patients in the control group were able to start active exercise with a significant delay when compared to the PRP treated subjects: 17 ± 7.2 days and 9 ± 3.8 days (p = 0.0001), respectively. This delay was mainly due to the persistence of pain in the subjects in the control group. The time necessary to return to walk without pain was significantly shorter in the PRP treated group: 24.27 ± 12.36 days versus 52.4 ± 20.03 days in the control group (p < 0.001) as well as the time needed to fully return to practice the previous sport activity: 53.33 ± 27.74 days versus 119.3 ± 43.87 days in the control group (p < 0.001).The present study showed that ultrasound guided delivery of PRP into the site of muscle injury has to be considered a valid therapeutic approach with the potentiality of significantly reduce time and costs for reaching a complete functional recovery.

Therapeutic efficacy of intra-articular hyaluronan derivative and platelet-rich plasma in mice following axial tibial loading.

ObjectiveTo investigate the therapeutic potential of intra-articular hyaluronan-derivative HYADD® 4-G and/or platelet-rich plasma (PRP) in a mouse model of non-invasive joint injury.MethodsNon-invasive axial tibial loading was used to induce joint injury in 10-week-old C57BL/6J mice (n = 86). Mice underwent a single loading of either 6 Newton (N) or 9N axial tibial compression. HYADD® 4-G was injected intra-articularly at 8 mg/mL or 15 mg/mL either before or after loading with or without PRP. Phosphate-buffered-saline was injected as control. Knee joints were harvested at 5 or 56 days post-loading and prepared for micro-computed tomography scanning and subsequently processed for histology. Immunostaining was performed for aggrecan to monitor its distribution, for CD44 to monitor chondrocyte reactive changes and for COMP (cartilage oligomeric matrix protein) as an index for cartilage matrix changes related to loading and cartilage injury. TUNEL assay was performed to identify chondrocyte apoptosis.ResultsLoading initiated cartilage proteoglycan loss and chondrocyte apoptosis within 5 days with slowly progressive post-traumatic osteoarthritis (no cartilage degeneration, but increased synovitis and ectopic calcification after 9N loading) at 56 days. Mice treated with repeated HYADD® 4-G (15 mg/mL) or HYADD® 4-G (8 mg/mL) ± PRP or PRP alone exhibited no significant improvement in the short-term (5 days) and long-term (56 days) consequences of joint loading except for a trend for improved bone changes compared to non-loaded joints.ConclusionWhile we failed to show an overall effect of intra-articular delivery of hyaluronan-derivative and/or PRP in reversing/protecting the pathological events in cartilage and synovium following joint injury, some bone alterations were relatively less severe with hyaluronan-derivative at higher concentration or in association with PRP.

Intratendon Delivery of Leukocyte-Poor Platelet-Rich Plasma Improves Healing Compared With Leukocyte-Rich Platelet-Rich Plasma in a Rabbit Achilles Tendinopathy Model

Background: Chronic tendinopathy is a commonly occurring clinical problem that affects both athletes and inactive middle-aged patients. Although some studies have shown that different platelet-rich plasma (PRP) preparations could exert various therapeutic effects in vitro, the role of leukocytes in PRP has not yet been defined under tendinopathy conditions in vivo. Purpose: This study compared the effects of the intratendon delivery of leukocyte-poor PRP (Lp-PRP) versus leukocyte-rich PRP (Lr-PRP) in a rabbit chronic tendinopathy model in vivo. Study Design: Controlled laboratory study. Methods: Four weeks after a local injection of collagenase in the Achilles tendon, the following treatments were randomly administered on the lesions: injections of (1) 200 μL of Lp-PRP (n = 8), (2) 200 μL of Lr-PRP (n = 8), or (3) 200 μL of saline (n = 8). Healing outcomes were assessed at 4 weeks after therapy with magnetic resonance imaging (MRI), cytokine quantification, real-time polymerase chain reaction analysis of gene expression, histology, and transmission electron microscopy (TEM). Results: MRI revealed that the Lr-PRP and saline groups displayed higher signal intensities compared with the Lp-PRP group with T2 mapping. Histologically, the Lp-PRP group displayed significantly better general scores compared with the Lr-PRP (P = .001) and saline (P < .001) groups. Additionally, TEM showed that the Lp-PRP group had larger collagen fibril diameters than the Lr-PRP group (P < .001). Enzyme-linked immunosorbent assay showed a significantly lower level of catabolic cytokine IL-6 in the Lp-PRP group compared with the Lr-PRP (P = .001) and saline (P = .021) groups. The Lp-PRP group displayed significantly increased expression of collagen I compared with the saline group (P = .004) but not the Lr-PRP group. Both the Lp-PRP and Lr-PRP groups exhibited significantly lower matrix metalloproteinase (MMP)–1 and MMP-3 expression levels compared with the saline group. However, only the Lp-PRP group displayed significantly higher expression of TIMP-1 than the saline group (P = .024). Conclusion: Compared with Lr-PRP, Lp-PRP improves tendon healing and is a preferable option for the clinical treatment of tendinopathy. Clinical Relevance: PRP is widely used in the clinical management of chronic tendinopathy. However, the clinical results are ambiguous. It is imperative to understand the influence of leukocytes on PRP-mediated tissue healing in vivo, which could facilitate the better clinical management of chronic tendinopathy. Further studies are needed to translate our findings to the clinical setting.

Site-specific targeting of platelet-rich plasma via superparamagnetic nanoparticles.

Background:Muscle strains are one of the most common injuries treated by physicians. Standard conservative therapy for acute muscle strains usually involves short-term rest, ice, and nonsteroidal anti-inflammatory medications, but there is no clear consensus regarding treatments to accelerate recovery. Recently, clinical use of platelet-rich plasma (PRP) has gained momentum as an option for therapy and is appealing for many reasons, most notably because it provides growth factors in physiological proportions and it is autologous, safe, easily accessible, and potentially beneficial. Local delivery of PRP to injured muscles can hasten recovery of function. However, specific targeting of PRP to sites of tissue damage in vivo is a major challenge that can limit its efficacy.Hypothesis:Location of PRP delivery can be monitored and controlled in vivo with noninvasive tools.Study Design:Controlled laboratory study.Methods:Superparamagnetic iron oxide nanoparticles (SPIONs) can be visualized by both magnetic resonance imaging (MRI) (in vivo) and fluorescence microscopy (after tissue harvesting). PRP was labeled with SPIONs and administered by intramuscular injections of SPION-containing platelets. MRI was used to monitor the ability to manipulate and retain the location of PRP in vivo by placement of an external magnet. Platelets were isolated from whole blood and incubated with SPIONs. Following SPION incubation with PRP, a magnetic field was used to manipulate platelet location in culture dishes. In vivo, the tibialis anterior (TA) muscles of anesthetized Sprague-Dawley rats were injected with SPION-containing platelets, and MRI was used to track platelet position with and without a magnet worn over the TA muscles for 4 days.Results:The method used to isolate PRP yielded a high concentration (almost 4-fold increase) of platelets. In vitro experiments showed that the platelets successfully took up SPIONs and then rapidly responded to an applied magnetic field. Platelets without SPIONs did not respond to the magnetic field. In vivo experiments showed that the SPION-containing platelets can be noninvasively maintained at a specific site with the application of a magnetic field.Conclusion:PRP may be a useful product in the clinical treatment of muscle injuries, but one problem with using it as a therapeutic tool is retaining PRP at the site of injury. This study proposes a potential solution, with findings that support this method at the cell, whole muscle, and in vivo levels. Controlling the location of PRP will allow the clustering of PRP to enrich the target area with growth factors and will prevent loss of platelets over time at the site of injury.

Platelet-rich plasma and skeletal muscle healing: a molecular analysis of the early phases of the regeneration process in an experimental animal model.

Platelet-rich plasma (PRP) has received increasing interest in applied medicine, being widely used in clinical practice with the aim of stimulating tissue healing. Despite the reported clinical success, there is still a lack of knowledge when considering the biological mechanisms at the base of the activity of PRP during the process of muscle healing. The aim of the present study was to verify whether the local delivery of PRP modulates specific molecular events involved in the early stages of the muscle regeneration process. The right flexor sublimis muscle of anesthetized Wistar rats was mechanically injured and either treated with PRP or received no treatment. At day 2 and 5 after surgery, the animals were sacrificed and the muscle samples evaluated at molecular levels. PRP treatment increased significantly the mRNA level of the pro-inflammatory cytokines IL-1β, and TGF-β1. This phenomenon induced an increased expression at mRNA and/or protein levels of several myogenic regulatory factors such as MyoD1, Myf5 and Pax7, as well as the muscular isoform of insulin-like growth factor1 (IGF-1Eb). No effect was detected with respect to VEGF-A expression. In addition, PRP application modulated the expression of miR-133a together with its known target serum response factor (SRF); increased the phosphorylation of αB-cristallin, with a significant improvement in several apoptotic parameters (NF-κB-p65 and caspase 3), indexes of augmented cell survival. The results of the present study indicates that the effect of PRP in skeletal muscle injury repair is due both to the modulation of the molecular mediators of the inflammatory and myogenic pathways, and to the control of secondary pathways such as those regulated by myomiRNAs and heat shock proteins, which contribute to proper and effective tissue regeneration.