KNEE

[2] Title: Effects of intraarticular IL1-Ra for acute anterior cruciate ligament knee injury: a randomized controlled pilot trial
Authors: Kraus, V.B., Birmingham, J., Stabler, T.V., Feng, S., Taylor, D.C., Moorman, C.T. 3rd, Garrett, W.E., Toth, A.P.
Published: Osteoarthritis and Cartilage, 2012; 20(4):271–278. doi:10.1016/j.joca.2011.12.009
Conclusion:  Overall, osteoarthritis is a complex disease involving inflammation, cartilage degradation, pain, and dysfunction of cellular organelles. The review highlights the need for new treatments that simultaneously target multiple disease mechanisms, offering the potential for more effective approaches to slowing OA progression and relieving symptoms.

[5] Title: Randomized, Placebo-Controlled Analysis of the Knee Synovial Environment Following Platelet-Rich Plasma Treatment for Knee Osteoarthritis
Authors: Tucker, J.D., Goetz, L.L., Duncan, M.B., Gilman, J.B., Elmore, L.W., Sell, S.A., McClure, M.J., Quagliano, P.V., Martin, C.C.
Published: PM&R, 2021 Jul;13(7):707-719. doi:10.1002/pmrj. 12561
Conclusion: We report significant changes for biomarker A2M (P= .005) as well as differences in expression of cellular markers and postulate that PRP modulates the local knee synovial environment by altering the inflammatory milieu, matrix degradation, and angiogenic growth factors. The PRP treatment group had less pain and stiffness and improved function scores.

[14] Title: Safety and Treatment Effectiveness of a Single Autologous Protein Solution Injection in Patients with Knee Osteoarthritis
Authors: van Drumpt, R.A.M., van der Weegen, W., King, W., Toler, K., Macenski, M.M.
Published: BioResearch Open Access, 2016;5(1):261–268. doi:10.1089/biores.2016.0014
Conclusion: In this small open-label study of 11 patients with early to moderate knee osteoarthritis, a single injection of nSTRIDE Autologous Protein Solution (APS) was safe, with no serious or device-related adverse events. Pain, stiffness, and function scores improved significantly by 2 weeks, and the WOMAC composite score was down about 70% at 3 and 6 months. At long-term follow-up (average 18 months, 6 patients), pain was still about 64% lower than baseline. Three of the 11 patients had a knee replacement after the study at 12, 12, and 24 months. There was no control group, and the sample was very small, so the authors call for a randomized trial. Funded by Biomet Biologics, and three authors are employed by Zimmer Biomet.

GENERAL

[1] Title: Osteoarthritis: molecular pathogenesis and potential therapeutic targets
Authors: Zhang, Y., Han, Y., Sun, Y., Hao, L., Gao, Y., Ye, J., Wang, H., Zhang, T., Liu, Y., Yang, Y.
Published: Signal Transduction and Targeted Therapy, 2026 
Conclusion:  The study demonstrates that treated glass beads can stimulate whole blood to produce significantly increased levels of anti-inflammatory cytokines, particularly IL-1Ra, without increasing pro-inflammatory cytokines. This approach may offer a promising autologous treatment strategy to reduce inflammation in osteoarthritis and other degenerative orthopedic conditions.

[3] Title: The production of anti-inflammatory cytokines in whole blood by physico-chemical induction
Authors: Meijer, H., Reinecke, J., Becker, C., Tholen, G., Wehling, P.
Published: Inflammation Research, 2003; 52(10):404–407. doi:10.1007/s00011-003-1197-1
Conclusion: In this small pilot trial, a single intra-articular injection of IL-1Ra (anakinra) shortly after acute ACL injury reduced pain and improved function over the short term compared with placebo. This supports the role of IL-1 in early post-injury joint symptoms and suggests IL-1 blockade could help modify early post-traumatic joint changes.

[4] Title: Independent Evaluation of ExoCube™ Device Using the Activation, Filtration, and Concentration Platform for Maximizing Deliverable Growth Factors from Autologous Blood
Authors: Bansal, H. (sole author; HB Specialty Hospital & Research Institute, India)
Published: Clinical White Paper, conference pre-print, 2026
Conclusion: EXOCUBE™ recovered up to 91% of platelets from whole blood, compared with about 40–60% for conventional single-spin systems. Glass-bead activation released the same growth factors as standard calcium activation. Concentration then raised most growth factors and proteins by about 3-fold, and A2M by about 5.8-fold, while inflammatory markers remained low. In vitro study of 5 healthy donors, sponsored by Plymouth Medical.

[7] Title: Breaking the Barrier in PRP Therapy: A Novel, Scalable Method to Generate Exosome-Rich PRP Secretome Suspensions with Enhanced In Vitro Regenerative Activity
Authors: Kul, Y., Duyan, C., Ünal, N., Canikyan, S., Tiryaki, T., Cohen, S.R., Yeni Kut, C., Yuvacı, A.U.
Published: EXOCUBE™ Research Paper, rev02, 2025
Conclusion: Glass-bead activation followed by tangential-flow concentration produced an exosome-enriched secretome. It had about 17.4× more exosome-range particles than plasma and the highest CD9/CD81 exosome positivity (69.57% vs. 46.94% in plasma). It also gave the most consistent fibroblast growth and the fastest wound closure in lab tests. The study used pooled plasma from 3 donors, and the authors disclose ties to LRI and Plymouth Medical.

[8] Title: Comparative Characterization of PRP-Derived Exosomes Isolated by Mechanical, Photothermal, and Bead-Mediated Tangential-Flow Platforms (ExoCube System)
Authors: Tiryaki, T., Cohen, S.R., Duncan, D., Schlaudraff, K.U., Ascher, B., Ghannam, S.F., Sterodimas, A., Canikyan, S., Duyan, C., Kul, Y.
Published: London Regenerative Institute Internal Study, 2025
Conclusion: In a head-to-head comparison, ExoCube outperformed Exomine and MCT across several key measures. It had the highest total protein (38.41 µg/mL), approximately 4.9× and 9.9× higher exosome concentrations than Exomine and MCT, an ideal exosome size of ~125 nm, and the highest CD9+/CD81+ positivity (89.3%). ExoCube also showed the strongest dermal fibroblast proliferation, although the study was limited to three healthy donors and in vitro testing.

SKIN/HAIR

[6] Title: Standardizing PRP-Derived Secretome Therapy: Scalable Processing and Case-Based Use in Dermatology and Hair Restoration
Authors: Yeni Kut, C., Tiryaki, T., Duncan, D., Ariano Junqueira, A.L., Cohen, S.R., Kul, Y., Duyan, C., Ünal, N., Canikyan, S.
Published: IntechOpen book chapter, 2026
Conclusion: EXOCUBE™ standardizes the production of a PRP-derived secretome in one closed workflow: bead activation, filtration, and tangential-flow concentration. In the case series, skin cases showed better texture, firmness, and pigmentation at 2–5 months, often after a single session. Hair cases (telogen effluvium and androgenetic alopecia) showed better density and scalp coverage at 3–6 months. The authors note that the evidence is still case-based and call for randomized controlled trials.

[9] Title: Development and Clinical Application of a Thermally Reconstructed Platelet-Rich Plasma Concentrate-Based Biofiller (ExoFiller)
Authors: Özbaba, A.N., Yeni Kut, C., Tiryaki, K.T., Cohen, S.R., Unal, N., Kul, Y., Duyan, C., Canikyan, S.
Published: Facial Plastic Surgery, 2026, doi:10.1055/a-2925-9527
Conclusion: ExoFiller is made by mechanically activating, concentrating, filtering, and heat-restructuring PRP. Compared with conventional PRP-Gel, it swelled better, broke down more slowly, was well tolerated by skin cells, and contained more regenerative mediators. In a 20-patient pilot, early observations suggested improved facial volume, contour, and skin quality with no adverse effects.

[10] Title: Illustrated Guide to Collagen Induction with Platelet-Rich Plasma (PRP): Rejuvenation of Face, Neck, Décolleté, Hands
Authors: Kolster, B.C., Paasch, U. (with the collaboration of Pototschnig, H.)
Published: Quintessence Publishing, 2019
Conclusion:  This textbook chapter explains how PRP growth factors stimulate skin fibroblasts and collagen production. It covers PRP use for rejuvenating the face, neck, décolleté, and hands, and for hair loss, and compares PRP preparation systems. It notes that results appear gradually over weeks to months.

[11] Title: Therapeutic Potential of Extracellular Vesicles (Exosomes) Derived from Platelet-Rich Plasma: A Literature Review Authors: Gupta, A.K., Wang, T., Rapaport, J.A., Talukder, M.
Published: Journal of Cosmetic Dermatology, 2025; 24(2):e16709
Conclusion: PRP-derived exosomes have strong preclinical support for wound healing, but evidence for hair growth and skin rejuvenation is still scarce. Exosomes from pooled, well-characterized allogeneic PRP could reduce variability between studies and give a clearer path to clinical validation. Exosomes are considered biologics and are not currently approved by any regulatory body worldwide. The authors call for research focused on transparency, reproducibility, and patient safety, and caution providers against administering exosomes until more research is done and a clear regulatory framework exists.

[12] Patient Observational Study To Evaluate Patient Experience Using III Biologic Exocube - Early Publication - October 2026. White Paper By Plymouth Medical. Data on file

[13] Breaking the Barrier in PRP Therapy: Comparative Analysis of Mechanically Activated and Non-Activated Exosomes Isolated by the Exocube™ System. Data on file

[15] Title: The Biological Role of Platelet Derivatives in Regenerative Aesthetics
Authors: Santos, L.C., Lana, G.L., Santos, G.S., Visoni, S.B.C., Brigagão, R.J., Santos, N., Sobreiro, R., da Cruz Silva Reis, A., Rodrigues, B.L., Ferrari, S., Tambeli, C.H., Lana, J.F.
Published: International Journal of Molecular Sciences, 2024; 25(11):5604. doi:10.3390/ijms25115604
Conclusion: Growth factors released from platelet-rich plasma (PRP) help restore hair by keeping hair-follicle cells alive longer, switching on follicle stem cells (FGF-7/β-catenin), and building up the blood supply around the follicle (VEGF, PDGF), which extends the growth (anagen) phase. In randomized, placebo-controlled trials of androgenetic alopecia, PRP significantly improved hair count, hair thickness and the share of follicles in the growth phase at 6 months, and a three-session trial added about 34 hairs in the target area (+46 hairs/cm²). Adding microneedling gave a greater hair count than PRP alone. Results have been mixed in some studies, and preparation methods are not yet standardized.

[16] Title: Insulin-like Growth Factor 1 (IGF-1) in Hair Regeneration: Mechanistic Pathways and Therapeutic Potential
Authors: Hsieh, W.-J., Qiu, W.-Y., Percec, I., Chang, T.-M.
Published: Current Issues in Molecular Biology, 2025; 47(9):773. doi:10.3390/cimb47090773
Conclusion: IGF-1 is a key growth factor for hair restoration. It is made mainly by dermal papilla cells, and it stimulates follicle cell growth, extends the growth (anagen) phase, and protects follicle cells from cell death. When IGF-1 was given topically or in a targeted way, hair density and follicle structure improved in androgenetic alopecia and alopecia areata, including significant gains in density and thickness with liposomal IGF-1 gels. IGF-1 appears to work even better alongside other growth factors (VEGF, FGF-7 and PDGF), which supports the case for multi-growth-factor therapy. Most of the evidence so far comes from lab and animal studies, so better delivery methods and long-term safety studies are still needed.