Enhanced osteochondral repair by leukocyte-depleted platelet-rich plasma in combination with adipose-derived mesenchymal stromal cells encapsulated in a three-dimensional photocrosslinked injectable hydrogel in a rabbit model.

INTRODUCTION: Intra-articular injection of adipose-derived mesenchymal stromal cells (ASCs) and/or platelet-rich plasma (PRP) have been reported to independently and synergistically improve healing of osteochondral lesions in animal models. However, their independent and combined effects when localized to an osteochondral lesion by encapsulation within a photocrosslinkable methacrylated gelatin hydrogel (GelMA) have not been explored. Herein we investigated a unique combination of allogeneic ASCs and PRP embedded in GelMA as a single-stage treatment for osteochondral regeneration in a rabbit model. METHODS: Thirty mature rabbits were divided into six experimental groups: (1) Sham; (2) Defect; (3) GelMA; (4) GelMA + ASCs; (5) GelMA + PRP; and (6) GelMA + ASCs + PRP.At 12 weeks following surgical repair, osteochondral regeneration was assessed on the basis of gross appearance, biomechanical properties, histological and immunohistochemical characteristics, and subchondral bone volume. RESULTS: In terms of mechanical property reflecting the ability of neotissue to bear stress, PRP only group were significantly lower than the Sham group (p = 0.0098). On the other hand, ASCs only and ASCs combined with PRP groups did not exhibit significantly difference, which suggesting that incorporation of ASCs assists in restoring the ability of the neotissue to bear stresses similarly to native tissue (p = 0.346, p = 0.40, respectively). Safranin O in ASCs combined with PRP group was significantly higher than the Defect and GelMA only groups (p = 0.0009, p = 0.0017, respectively). Additionally, ASCs only and ASCs combined with PRP groups presented especially strong staining for collagen type II. Surprisingly, PRP only and PRP + ASCs groups tended to exhibit higher collagen type I and collagen type X staining compared to ASCs only group, suggesting a potential PRP-mediated hypertrophic effect. CONCLUSION: Regeneration of a focal osteochondral defect in a rabbit model was improved by a single-stage treatment of a photocrosslinked hydrogel containing allogenic ASCs and autologous PRP, with the combination of ASCs and PRP producing superior benefit than either alone. No experimental construct fully restored all properties of the native, healthy osteochondral unit, which may require longer follow-up or further modification of PRP and/or ASCs characteristics.

The efficacy of platelet rich plasma in the treatment of erectile dysfunction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Erectile dysfunction (ED) is a common issue among males, and the use of platelet-rich plasma (PRP) therapy for treating ED has gained increasing attention, but there is still no conclusive evidence regarding its efficacy. AIM: To evaluate the efficacy of PRP therapy for ED. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases up to November 2023 to identify randomized controlled trials (RCTs) on PRP therapy for ED. We used Review Manager version 5.4 for data analysis and management. RESULT: After applying inclusion and exclusion criteria for screening, a total of 4 studies involving 413 patients were finally included in our meta-analysis. According to our analysis, the PRP group showed significant advantages over the placebo group in terms of MCID at the first month (p = 0.03) and sixth months (p = 0.008), while there was no significant difference between the two groups at the third month (p = 0.19). Additionally, in terms of IIEF, PRP showed significantly better efficacy than placebo at the first, third, and sixth months (p < 0.00001). CONCLUSIONS: PRP shows more effectiveness in treating ED compared to placebo, offering hope as a potential alternative treatment for ED.

In vitro studies on the effects of cryopreserved platelet-rich plasma on cells related to wound healing.

Platelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP's bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP's IL-1ß levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.

What is the context? Platelet-rich plasma (PRP) is a potential bioactive material for wound healing, but using it immediately faces issues like volume, concentration, and consistency.Low-temperature freezing is a method employed to preserve PRP. However, the current understanding of the effects of the freezing-thawing process on the components of PRP and its impact on cells relevant to wound healing remains unclear.What is new? This study explores the feasibility and effectiveness of using cryopreserved PRP at −80°C for promoting wound healing. This research stands out for its focus on cellular responses and practical implications in therapeutic contexts.To understand their distinct impact on different cell types relevant to wound healing, the study meticulously examined various final concentrations of cPRP (1%, 5%, 10%).The study identified the superior effects of 5% cPRP on crucial cellular activities, notably in cell polarization, proliferation, angiogenesis, and migration.What is the impact? Low-temperature freezing can be considered an effective method for PRP preservation.Some bioactive components in cPRP exhibit subtle changes; however, these changes result in better effects on certain cell types related to healing.The study illustrates that all concentrations of cPRP effectively enhance cell proliferation, migration, and differentiation, emphasizing the comparable efficacy of cryopreserved PRP to non-cryopreserved PRP.

Translational Research on Orthobiologics in the Treatment of Rotator Cuff Disease: From the Laboratory to the Operating Room.

Rotator cuff disease is one of the most common human tendinopathies and can lead to significant shoulder dysfunction. Despite efforts to improve symptoms in patients with rotator cuff tears and healing rates after rotator cuff repair, high rates of failed healing and persistent shoulder morbidity exist. Increasing interest has been placed on the utilization of orthobiologics-scaffolds, cell-based augmentation, platelet right plasma (platelet-rich plasma), and small molecule-based strategies-in the management of rotator cuff disease and the augmentation of rotator cuff repairs. This is a complex topic that involves novel treatment strategies, including patches/scaffolds, small molecule-based, cellular-based, and tissue-derived augmentation techniques. Ultimately, translational research, with a particular focus on preclinical models, has allowed us to gain some insights into the utility of orthobiologics in the treatment of rotator cuff disease and will continue to be critical to our further understanding of the underlying cellular mechanisms moving forward.

Characterization of distinct microbiota associated with androgenetic alopecia patients treated and untreated with platelet-rich plasma (PRP).

BACKGROUND: Androgenic alopecia (AGA) is the most common type of hair loss in men, and there are many studies on the treatment of hair loss by platelet-rich plasma (PRP). The human scalp contains a huge microbiome, but its role in the process of hair loss remains unclear, and the relationship between PRP and the microbiome needs further study. Therefore, the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota composition. METHODS: We performed PRP treatment on 14 patients with AGA, observed their clinical efficacy, and collected scalp swab samples before and after treatment. The scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3-V4 region of the 16 s RNA gene and sequencing for bacterial identification. RESULTS: The results showed that PRP was effective in the treatment of AGA patients, and the hair growth increased significantly. The results of relative abundance analysis of microbiota showed that after treatment, g_Cutibacterium increased and g_Staphylococcus decreased, which played a stable role in scalp microbiota. In addition, g_Lawsonella decreased, indicating that the scalp oil production decreased after treatment. CONCLUSIONS: The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing.

The varying clinical effectiveness of single, three and five intraarticular injections of platelet-rich plasma in knee osteoarthritis.

OBJECTIVE: To investigate the variations in clinical effectiveness among patients diagnosed with knee osteoarthritis who underwent intra-articular administration of platelet-rich plasma using single, triple, or quintuple injections. METHODS: One hundred twenty patients with grade I-III knee osteoarthritis were randomly assigned to three groups: PRP1 group, who received a single injection of platelet-rich plasma; PRP3 group, who received three PRP injections one week apart; PRP5 group, who received five PRP injections one week apart. The patients' conditions were evaluated using the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index-VA3.1 version (WOMAC-VA3.1) at baseline and 6, 12, 24, and 52 weeks 52 weeks follow up. RESULTS: Out of the total participants, 106 patients (30 males and 76 females) completed the study. The primary outcome measure, WOMAC pain score, registered significant improvements across all groups when compared to pre-treatment levels. However, the application of 3 and 5 injections of platelet-rich plasma was substantially more effective than that of a single injection in reducing knee pain and stiffness, as well as enhancing physical function in patients with knee osteoarthritis. No statistically discernable difference was observed between PRP3 and PRP5 at all follow-up intervals, and there was no discernable difference between 3 and 5 PRP injections either. Mild side effects occurred in all three groups. CONCLUSIONS: The administration of three or five injections of platelet-rich plasma is safe, substantially more effective than single injections, and leads to remarkable clinical improvement by significantly reducing knee pain, improving joint stiffness, and enhancing physical function in patients with grade I-III knee osteoarthritis. Furthermore, no significant difference was observed in the efficacy of three or five injections. Therefore, we recommend using three injections of PRP in the treatment of patients with knee osteoarthritis of grade I-III.

Regenerative Medicine Solutions for Rotator Cuff Injuries in Athletes: Indications and Outcomes.

Rotator cuff (RC) injuries include a wide range of pathologic states. Athletes are perhaps the most susceptible to RC injuries ranging from tendinopathy to partial or full-thickness tears, due to functional overload and repetitive movements, causing abstention from sports for long periods. Regenerative medicine keeps giving us multiple choices to fight the disability caused by these pathologies. A literature search was performed, and findings related to the structure-function of rotator cuff units, pathophysiology of injuries, regenerative medicine treatments, and future strategies were outlined. Platelet-rich plasma (PRP) has a greater number of articles and clinical trials, accompanied by stem cells progenitor, prolotherapy, and new approaches such as microfragmented adipose tissue and exosomes. RC injuries in athletes can cause pain, functional impotence, and the risk of recurrence, and can lead them to stop playing sports. Regenerative medicine offers a range of treatments, but some of them need further studies to underline their actual validity.

The role of platelet rich plasma enriched fat graft for correction of deformities after conservative breast surgery.

BACKGROUND: Fat transfer has been widely used after breast conservative surgery (BCS) where it aims to recover shapes as a simple, inexpensive, biocompatible method but the technique is not without complications. Platelet Rich Plasma (PRP) is a promising approach to enhance fat graft survival and subsequently improve the outcome. The aim of this study was to evaluate the effect of enriching fat graft with PRP for delayed correction of deformities after conservative surgery for breast cancer regarding esthetic outcome and incidence of complications. METHODS: The current study included 50 female patients who were scheduled for delayed lipofilling for correction of deformities after conservative surgery for breast cancer. The studied patients were randomly allocated into 2 groups: Group I (G I) included 25 patients scheduled for PRP enriched lipoinjection and Group II (G II) included 25 patients scheduled for lipoinjection without PRP as a control group. RESULTS: Number of sessions of lipoinjection was significantly less in G I in comparison to G II (P = 0.024). During the 2nd session; the amounts of fat injected and harvested were significantly less in G I in comparison to G II (P = 0.049 and 0.001 respectively). Recipient site complications were significantly more evident in G II in comparison to G I (P = 0.01). Surgeon and patient satisfactions were significantly more evident in GI in comparison to G II (P = 0.005 and 0.029 respectively). CONCLUSION: The addition of PRP to fat grafts is a simple, cost-effective and safe method to improve esthetic outcome and decrease complications.

Platelet-rich plasma alleviates neuropathic pain in osteoarthritis by downregulating microglial activation.

BACKGROUND: The development of neuropathic pain (NP) is one of the reasons why the pain is difficult to treat, and microglial activation plays an important role in NP. Recently, platelet-rich plasma (PRP) has emerged as a novel therapeutic method for knee osteoarthritis (KOA). However, it's unclarified whether PRP has analgesic effects on NP induced by KOA and the underlying mechanisms unknown. PURPOSE: To observe the analgesic effects of PRP on NP induced by KOA and explore the potential mechanisms of PRP in alleviating NP. METHODS: KOA was induced in male rats with intra-articular injections of monosodium iodoacetate (MIA) on day 0. The rats received PRP or NS (normal saline) treatment at days 15, 17, and 19 after modeling. The Von Frey and Hargreaves tests were applied to assess the pain-related behaviors at different time points. After euthanizing the rats with deep anesthesia at days 28 and 42, the corresponding tissues were taken for subsequent experiments. The expression of activating transcription factor 3 (ATF3) in dorsal root ganglia (DRG) and ionized-calcium-binding adapter molecule-1(Iba-1) in the spinal dorsal horn (SDH) was detected by immunohistochemical staining. In addition, the knee histological assessment was performed by hematoxylin-eosin (HE) staining. RESULTS: The results indicated that injection of MIA induced mechanical allodynia and thermal hyperalgesia, which could be reversed by PRP treatment. PRP downregulated the expression of ATF3 within the DRG and Iba-1 within the SDH. Furthermore, an inhibitory effect on cartilage degeneration was observed in the MIA + PRP group only on day 28. CONCLUSION: These results indicate that PRP intra-articular injection therapy may be a potential therapeutic agent for relieving NP induced by KOA. This effect could be attributed to downregulation of microglial activation and reduction in nerve injury.

Molybdesum selenide-based platelet-rich plasma containing carboxymethyl chitosan/polyvinyl pyrrolidone composite antioxidant hydrogels dressing promotes the wound healing.

Excess free radicals at the wound site can cause an inflammatory response, which is not conducive to wound healing. Hydrogels with antioxidant properties can prevent inflammatory storms by scavenging free radicals from the wound site and inhibiting the release of inflammatory factors. In this study, we prepared the carboxymethyl chitosan (CMCS)/polyvinyl pyrrolidone (PVP)/Molybdenum (IV) Selenide (MoSe2), and platelet-rich plasma (PRP) (CMCS/PVP/MoSe2/PRP) hydrogels for accelerating the repair of wounds. In the hydrogels, the MoSe2 can scavenge various free radicals to reduce oxidative stress at the site of inflammation, endowed the hydrogels with antioxidant properties. Interestingly, growth factors released by PRP assisted the tissue repair by promoting the formation of new capillaries. CMCS as a backbone not only showed good biocompatibility and biodegradability but also played a significant role in maintaining the sustained release of growth factors. In addition, incorporating PVP enhanced the tissue adhesion and mechanical properties. The multifunctional composite antioxidant hydrogels have good swelling properties and biodegradability, which is completely degraded within 28 days. Thus, the antioxidant CMCS/PVP/MoSe2/PRP hydrogels provide a new idea for designing ideal multifunctional wound dressings.

Fixation with multiple K-wires and PRP injection as an effective way to manage heel pad avulsion.

The treatment of acute heel pad avulsion differs significantly from managing other soft tissue injuries due to its unique soft tissue structure. This case report outlines a scenario involving a male in his 20s who suffered heel pad avulsion without a calcaneal fracture but with an ipsilateral medial malleolus fracture after a twisting injury to the ankle caused by a road traffic accident. Immediate action was taken within 24 hours of the injury, involving thorough debridement of the wound, fixation to the calcaneum using multiple K-wires, primary suturing and internal fixation of the medial malleolus with two cannulated cancellous screws. Postoperative care included PRP (platelet-rich plasma) injections into the wound twice, removal of K-wires after 6 weeks and allowing walking with full weight bearing after 8 weeks. A year later, the wound had completely healed, and the patient was comfortably walking pain-free with full weight-bearing capabilities.

Fat Grafting and Regenerative Medicine in Burn Care.

Regenerative therapies such as fat grafting and Platelet Rich Plasma (PRP) have emerged as new options to tackle burn-related injuries and their long-term sequelae. Fat grafting is able to promote wound healing by regulating the inflammatory response, stimulating angiogenesis, favoring the remodeling of the extracellular matrix, and enhancing scar appearance. PRP can enhance wound healing by accelerating stages including hemostasis and re-epithelization. It can improve scar quality and complement fat grafting procedures. Their cost-effectiveness, minimal invasiveness, and promising results observed in the literature have made these tools as therapeutic candidates. The current evidence on fat grafting and PRP in acute and reconstructive burns is described and discussed in this study.

Clinical evaluation of platelet-rich plasma therapy for osteonecrosis of the femoral head: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to assess the efficacy and safety of platelet-rich plasma (PRP) for osteonecrosis of the femoral head (ONFH). METHODS: We comprehensively searched randomized controlled trials in PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, China Science and Technology Journal Database, WanFang, and Chinese BioMedical Literature Database from inception until October 25, 2024. The literature on the clinical efficacy of autologous PRP for ONFH was collated. According to the inclusion and exclusion criteria, the literature was screened, quality evaluated and the data was extracted. Meta-analysis was carried out with the software Review Manager 5.4.1 software and Stata 17.0 software. In addition, potential publication bias was detected by the funnel plot test and Egger's test. The GRADE system was used to evaluate the quality of evidence for outcome indicators. RESULTS: Fourteen studies involving 909 patients were included in this study. Compared with non-PRP, PRP exhibited significant improvements in the Harris hip score (HHS) at 3 months (MD = 3.58, 95% Cl: 1.59 to 5.58, P = 0.0004), 6 months (MD = 6.19, 95% Cl: 3.96 to 8.41, P < 0.00001), 12 months (MD = 4.73, 95% Cl: 3.24 to 6.22, P < 0.00001), ≥ 24 months (MD = 6.83, 95% Cl: 2.09 to 11.59, P = 0.0003), and the last follow-up (MD = 6.57, 95% Cl: 4.81 to 8.33, P < 0.00001). The PRP also showed improvement in HHS compared to baseline than the non-PRP at 3 months (MD = 3.60, 95% Cl: 1.26 to 5.94, P = 0.003), 6 months (MD = 6.17, 95% Cl: 3.74 to 8.61, P < 0.00001), 12 months (MD = 5.35, 95% Cl: 3.44 to 7.25, P < 0.00001), ≥ 24 months (MD = 8.19, 95% Cl: 3.76 to 12.62, P = 0.0003), and the last follow-up (MD = 6.94, 95% Cl: 5.09 to 8.78, P < 0.00001). The change in visual analog scale (VAS) score 3 months post intervention (MD = -0.33, 95% Cl: -0.52 to -0.13, P = 0.001), 6 months (MD = -0.69, 95% Cl: -0.90 to -0.48, P < 0.00001), 12 months (MD = -0.75, 95% Cl: -1.05 to -0.46, P < 0.00001), ≥ 24 months (MD = -1.05, 95% Cl: -1.20 to -0.89, P < 0.00001), and the last follow-up (MD = -0.75, 95% Cl: -0.97 to -0.54, P < 0.00001). The PRP also showed a decrease in VAS score compared to baseline than the non-PRP at 3 months (MD = -0.29, 95% Cl: -0.41 to -0.17, P = 0.003), 6 months (MD = -0.63, 95% Cl: -0.96 to -0.30, P = 0.0002), 12 months (MD = -0.78, 95% Cl: -1.22 to -0.33, P = 0.0006), ≥ 24 months (MD = -1.11, 95% Cl: -1.27 to -0.96, P < 0.00001), and the last follow-up (MD = -0.74, 95% Cl: -1.05 to -0.43, P < 0.00001). Additionally, it was found that the PRP group had the advantages in the following aspects: collapse rate of the femoral head (RR = 0.33, 95% Cl: 0.17 to 0.62, P = 0.0006), rate of conversion to total hip arthroplasty (RR = 0.37, 95% Cl: 0.18 to 0.74, P = 0.005), and overall complications (RR = 0.33, 95% Cl: 0.13 to 0.83, P = 0.02). The GRADE evidence evaluation showed overall complication as very low quality and other indicators as low quality. CONCLUSION: There is limited evidence showing benefit of PRP therapy for treatment of ONFH patients, and most of this evidence is of low quality. Caution should therefore be exercised in interpreting these results. It is recommended that future research involve a greater number of high-quality studies to validate the aforementioned conclusions. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/ #recordDetails, CRD42023463031.

Arthroscopic rotator cuff repair combined with platelet-rich plasma products can reduce the rate of retearing and improve clinical outcomes: A meta-analysis of randomized controlled trials.

BACKGROUND: Although several studies on the potential benefits of protein-rich plasma (PRP) therapy for rotator cuff injuries have been published, the results have been conflicting. Therefore, this study aimed to determine whether PRP is beneficial for the prevention of retears after arthroscopic rotator cuff repair (ARCR). METHODS: Two reviewers conducted independent literature searches based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials (RCTs) comparing a PRP treatment group with a control group were included. The quality of evidence was assessed using the Cochrane Collaboration Risk of Bias Tool. Clinical outcomes were compared using the risk ratio (RR) for dichotomous variables and weighted mean difference (WMD) for continuous variables. Statistical significance was set at P < .05. RESULTS: This review included 21 RCTs (1359 patients). Significant results were noted in favor of PRP treatment compared with controls based on retearing rates (16.5% vs 23.6%, respectively; P = .002) and the Constant score in the short term (WMD: 1.98; 95% confidence interval [CI], 0.27-3.70; I2 = 0%; P = .02), medium term and long term (WMD: 2.56 [95% CI: 1.57-3.55]; I2 = 2%; P < .001); the University of California, Los Angeles score in the short term (WMD: 1.14 [95% CI: 0.43-1.85]; I2 = 25%; P = .002) but not in the medium and long term (WMD: 0.66 [95% CI: -0.16 to 1.48]; I2 = 57%; P = .11); and the visual analog scale score in the short term (WMD: -0.63 [95% CI: -0.83 to-0.43]; I2 = 41%; P < .001), medium and long term (WMD: -0.12 [95% CI: -0.19 to-0.05]; I2 = 0%; P = .008). There was no significant difference in American Shoulder and Elbow Surgeons scores between the treatment and control groups in the short term (WMD: -0.48 [95% CI: -2.80 to 1.85]; I2 = 22%; P = .69) or medium and long term (WMD: 0.92 [95% CI: -1.56 to 3.39]; I2 = 40%; P = .47). CONCLUSION: Intraoperative use of PRP reduces the risk of rotator cuff repair failure, improves clinical outcomes, and reduces recurrence rates.

Identification of unapproved orthopedic regenerative medicine: Usefulness of the Act on Safety of Regenerative Medicine.

In Japan, the Act on Safety of Regenerative Medicine regulates unapproved regenerative medicine. Other nations market regenerative medicine products, bypassing regulatory approval. To identify unapproved orthopedic regenerative medicine, we have used data based on the Act. Platelet-rich plasma was often used. The common target was the knee. Prices averaged $2,490.

Assessing Bioprinted Functionalized Grafts for Biological Tendon Augmentation In Vitro.

Tendinopathy, characterized by inflammatory and degenerative changes, presents challenges in sports and medicine. In addressing the limitations of conservative management, this study focuses on developing tendon grafts using extrusion bioprinting with platelet-rich plasma (PRP)-infused hydrogels loaded with tendon cells. The objective is to understand paracrine interactions initiated by bioprinted tendon grafts in either inflamed or non-inflamed host tissues. PRP was utilized to functionalize methacrylate gelatin (GelMA), incorporating tendon cells for graft bioprinting. Bioinformatic analyses of overexpressed proteins, predictive of functional enrichment, revealed insights into PRP graft behavior in both non-inflamed and inflamed environments. PRP grafts activated inflammatory pathways, including Interleukin 17 (IL-17), neuroinflammation, Interleukin 33 (IL-33), and chemokine signaling. Interleukin 1 beta (IL-1b) in the graft environment triggered p38 mitogen-activated protein kinase (MAPK) signaling, nuclear factor kappa light chain enhancer of activated B cells (NF-kB) canonical pathway, and Vascular Endothelial Growth Factor (VEGF) signaling. Biological enrichment attributed to PRP grafts included cell chemotaxis, collagen turnover, cell migration, and angiogenesis. Acellular PRP grafts differed from nude grafts in promoting vessel length, vessel area, and junction density. Angiogenesis in cellular grafts was enhanced with newly synthesized Interleukin 8 (IL-8) in cooperation with IL-1b. In conclusion, paracrine signaling from PRP grafts, mediated by chemokine activities, influences cell migration, inflammation, and angiogenic status in host tissues. Under inflammatory conditions, newly synthesized IL-8 regulates vascularization in collaboration with PRP.

An In Vitro Study on the Application of Silver-Doped Platelet-Rich Plasma in the Prevention of Post-Implant-Associated Infections.

Implant therapy is a common treatment option in dentistry and orthopedics, but its application is often associated with an increased risk of microbial contamination of the implant surfaces that cause bone tissue impairment. This study aims to develop two silver-enriched platelet-rich plasma (PRP) multifunctional scaffolds active at the same time in preventing implant-associated infections and stimulating bone regeneration. Commercial silver lactate (L) and newly synthesized silver deoxycholate:ß-Cyclodextrin (B), were studied in vitro. Initially, the antimicrobial activity of the two silver soluble forms and the PRP enriched with the two silver forms has been studied on microbial planktonic cells. At the same time, the biocompatibility of silver-enriched PRPs has been assessed by an MTT test on human primary osteoblasts (hOBs). Afterwards, an investigation was conducted to evaluate the activity of selected concentrations and forms of silver-enriched PRPs in inhibiting microbial biofilm formation and stimulating hOB differentiation. PRP-L (0.3 µg/mm2) and PRP-B (0.2 µg/mm2) counteract Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans planktonic cell growth and biofilm formation, preserving hOB viability without interfering with their differentiation capability. Overall, the results obtained suggest that L- and B-enriched PRPs represent a promising preventive strategy against biofilm-related implant infections and demonstrate a new silver formulation that, together with increasing fibrin binding protecting silver in truncated cone-shaped cyclic oligosaccharides, achieved comparable inhibitory results on prokaryotic cells at a lower concentration.

Intra-Articular Platelet-Rich Plasma Injection After Anterior Cruciate Ligament Reconstruction: A Randomized Clinical Trial.

Importance: Platelet-rich plasma (PRP) has been considered a promising treatment for musculoskeletal disorders. The effects of PRP on clinical outcomes of anterior cruciate ligament reconstruction (ACLR) are controversial. Objective: To compare subjective outcomes and graft maturity in patients undergoing ACLR with and without postoperative intra-articular PRP injection. Design, Setting, and Participants: This surgeon- and investigator-masked randomized clinical trial included patients treated at a national medical center in China who were aged 16 to 45 years and scheduled to undergo ACLR. Participants were enrolled between March 21, 2021, and August 18, 2022, and followed up for 12 months, with the last participant completing follow-up on August 28, 2023. Interventions: Participants were randomized 1:1 to the PRP group (n = 60), which received 3 doses of postoperative intra-articular PRP injection at monthly intervals, or to the control group (n = 60), which did not receive postoperative PRP injection. Both groups had the same follow-up schedule. Main Outcomes and Measures: The primary outcome was the mean score for 4 subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) (range, 0-100, with higher scores indicating better knee function and fewer symptoms) at 12 months postoperatively. Secondary outcomes were patient-reported outcomes, graft maturity (on magnetic resonance imaging), and physical examinations at 3, 6, and 12 months. Results: Among the 120 randomized participants (mean [SD] age, 29.0 [8.0] years; 84 males [70%]), 114 (95%) were available for the primary outcome analysis. The mean KOOS4 scores at 12 months were 78.3 (SD, 12.0; 95% CI, 75.2-81.4) in the PRP group and 76.8 (SD, 11.9; 95% CI, 73.7-79.9) in the control group (adjusted mean between-group difference, 2.0; 95% CI, -2.3 to 6.3; P = .36). Secondary outcomes were not statistically significantly different between the 2 groups except for sports and recreation level and graft maturity at 6 months. Intervention-related adverse events included pain at the injection site and knee swelling after injection. Conclusions and Relevance: In this randomized clinical trial among patients undergoing ACLR, the addition of postoperative intra-articular PRP injection did not result in superior improvement of knee symptoms and function at 12 months compared with no postoperative injection. Further studies are required to determine appropriate indications for PRP in musculoskeletal disorders. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000040262.

A randomised Trial of Autologous Blood products, leukocyte and platelet-rich fibrin (L-PRF), to promote ulcer healing in LEprosy: The TABLE trial.

INTRODUCTION: Autologous blood products like Platelet Rich Plasma (PRP) and Leukocyte and Platelets Rich Fibrin (L-PRF) have been used for many years across many types of skin ulcers. However, the effectiveness of autologous blood products on wound healing is not well established. METHODS: We evaluated the 'second generation' autologous product- Leukocyte and Platelet- Rich Fibrin (L-PRF). Our trial was undertaken on patients suffering from neuropathic leprosy ulcers at the Anandaban hospital which serves the entire country of Nepal. We conducted a 1:1 (n = 130) individually randomised trial of L-PRF (intervention) vs. normal saline dressing (control) to compare rate of healing and time to complete healing. Rate of healing was estimated using blind assessments of ulcer areas based on three different measurement methods. Time to complete healing was measured by the local unblinded clinicians and by blind assessment of ulcer images. RESULTS: The point estimates for both outcomes were favourable to L-PRF but the effect sizes were small. Unadjusted mean differences (intervention vs control) in mean daily healing rates (cm2) were respectively 0.012 (95% confidence interval 0.001 to 0.023, p = 0.027); 0.016 (0.004 to 0.027, p = 0.008) and 0.005 (-0.005 to 0.016, p = 0.313) across the three measurement methods. Time to complete healing at 42 days yielded Hazard Ratios (unadjusted) of 1.3 (0.8 to 2.1, p = 0.300) assessed by unblinded local clinicians and 1.2 (0.7 to 2.0, p = 0.462) on blind assessment. CONCLUSION: Any benefit from L-PRF appears insufficient to justify routine use in care of neuropathic ulcers in leprosy. TRIAL REGISTRATION: ISRCTN14933421. Date of trial registration: 16 June 2020.