Leonardo P. Oliveira

Background/Objectives: Platelet-rich plasma (PRP) has been extensively used in clinical practice to treat musculoskeletal (MSK) and spinal maladies. PRP applications and preparation methods focus on variables such as delivery technique, formulation, and device performance. Few PRP preparation methods consider the variability in the biological status of the individual patient following a comprehensive homeostatic tissue repair response. In recent years, more information has become available for addressing the efficacy of PRP devices and preparation methods. Furthermore, the impact of the PRP dose and bioformulation on different pathoanatomical tissues and patient outcomes has been more widely discussed. This review aims to examine different variables in the optimization of PRP preparation methods, focusing on several platelet indices that influence hematopoiesis, subsequent to homeostasis and neuronal regulation, and how this relates to the release of platelets with variable densities, the mean platelet volume (MPV), platelet distribution width (PDW), and ultimately platelet concentration. Methods: A literature review was conducted using the PubMed, Medline, and Cochrane databases. Results: The literature indicates that the overall physiological platelet dynamics, from bone marrow megakaryocytes to peripheral blood release, differ continuously between health and disease. This study demonstrates that variations in platelet density, as indicated by mean platelet volume (MPV), and platelet count are associated with deviations in the total platelet distribution width. Conclusions: Incorporating platelet indices (PIs) into platelet-rich plasma (PRP) preparation protocols and methodologies is recommended to optimize the recovery of denser, more reactive, and regenerative platelets inherent in peripheral blood, which are integral to the patient’s homeostatic tissue repair mechanisms. Pre-procedural assessment of the patient’s platelet biological status allows for the preservation of an optimal platelet profile within PRP preparations, potentially enhancing clinical efficacy.

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Background: Osteoarthritis is a leading cause of disability worldwide, and cell‐based treatments including adipose‐derived and bone marrow aspirate have been sought by the lay and medical community as treatment options. Objective: To perform a scoping review of published literature on cell‐based injections allowed by the U.S. Food and Drug Administration for the treatment of osteoarthritis to synthesize existing evidence and identify research gaps for future evaluation. Methods: A comprehensive search of five databases was executed from inception through January 2, 2025. Studies that met the inclusion criteria were original research studies written in English on Food and Drug Administration‐allowed cell‐based treatments in adults with osteoarthritis of any joint. Results: The database search yielded 4257 unique records. After screening, 84 studies met the inclusion criteria, encompassing 9996 patients and a total of 10,508 procedures. The primary research study designs were cohort studies ( n = 62), focused on treatment of knee osteoarthritis ( n = 63), and described bone marrow aspirate ( n = 42) and adipose‐derived ( n = 42) treatments. Postprocedure monitoring ranged from 6 weeks to 5 years, with most studies ≤1 year ( n = 59). Patient‐reported outcomes were reported in 83 of 84 studies; few provided imaging outcomes including magnetic resonance imaging ( n = 9) or radiographs ( n = 2). Conclusion: This review identified limited randomized controlled trials, limited studies outside the knee, limited description of cell‐based treatments, and treatment protocols, along with inconsistent patient‐reported outcomes limited to 1 year in most studies. We propose establishing reporting guidelines in research on cell‐based therapies.

Glenohumeral osteoarthritis (GHOA) presents significant challenges for patients, often resulting in debilitating pain, stiffness, and progressive loss of function. While conventional non-operative treatments such as physical therapy, medications, and corticosteroid injections can provide relief, their benefits may diminish over time. For many patients, total shoulder arthroplasty may not be a viable option due to associated risks or the demands of an extensive recovery process. This leaves a critical need for alternative innovative and effective treatment options. The synergistic pairing of brisement and PT aims to improve range of motion, reduce pain, and enhance strength and function. This approach has the potential to fill gaps in the current treatment landscape for GHOA. The purpose of this clinical commentary is to introduce a novel treatment approach combining brisement, an ultrasound-guided hydrodilatation procedure, with a structured physical therapy program to manage GHOA.

There are limited data on the use of mesenchymal stem cell injections for hip osteoarthritis. The goal of this study was to evaluate the literature by analyzing outcomes and comparing methodologies...

To examine the impact of polyphenol supplementation on the recruitment, mobilization and activation of monocyte subsets following resistance exercise. Thirty-eight recreationally active males (22.1 ± 3.1 yrs; 173.9 ± 7.9 cm; 77.8 ± 14.5 kg) were assigned to 28-days of polyphenol supplementation (PPB), placebo (PL) or control (CON). Blood samples were obtained before (PRE), immediately-(IP), one-(1H), five-(5H), 24-(24H) and 48-(48H) hours post-resistance exercise (PPB/PL) or rest (CON). Fine-needle biopsies were obtained from the vastus lateralis at PRE, 1H, 5H and 48H. Circulating concentrations of macrophage chemoattractant protein-1 (MCP-1) and fractalkine, as well as intramuscular MCP-1 were analyzed via multiplex assay. Changes in the proportions and expression of CD11b on monocyte subsets were assessed via flow cytometry. Circulating MCP-1 increased in PPB and PL at IP with further increases at 5H. Intramuscular MCP-1 was increased at 1H, 5H and 48H in all groups. Classical monocyte proportions were reduced in PPB and PL at IP, and increased at 1H. Nonclassical monocytes were increased in PPB and PL at IP, while intermediate monocytes were increased at IP, and reduced at 1H. Intermediate monocytes were increased in PPB at 24H and 48H. CD11b expression was reduced on PPB compared to PL and CON at PRE on intermediate and nonclassical monocytes. Resistance exercise may elicit selective mobilization of intermediate monocytes at 24H and 48H, which may be mediated by tissue damage. Additionally, polyphenol supplementation may suppress CD11b expression on monocyte subsets at rest.

β-alanine supplementation increases muscle carnosine content and improves anaerobic exercise performance by enhancing intracellular buffering capacity. β-alanine ingestion in its traditional rapid-release formulation (RR) is associated with the symptoms of paresthesia. A sustained-release formulation (SR) of β-alanine has been shown to circumvent paresthesia and extend the period of supply to muscle for carnosine synthesis. The purpose of this investigation was to compare 28 days of SR and RR formulations of β-alanine (6 g day⁻¹) on changes in carnosine content of the vastus lateralis and muscle fatigue. Thirty-nine recreationally active men and women were assigned to one of the three groups: SR, RR, or placebo (PLA). Participants supplementing with SR and RR formulations increased muscle carnosine content by 50.1% (3.87 mmol kg⁻¹ww) and 37.9% (2.62 mmol kg⁻¹ww), respectively. The change in muscle carnosine content in participants consuming SR was significantly different (p = 0.010) from those consuming PLA, but no significant difference was noted between RR and PLA (p = 0.077). Although participants ingesting SR experienced a 16.4% greater increase in muscle carnosine than RR, fatigue during maximal voluntary isometric contractions was significantly attenuated in both SR and RR compared to PLA (p = 0.002 and 0.024, respectively). Symptoms of paresthesia were significantly more frequent in RR compared to SR, the latter of which did not differ from PLA. Results of this study demonstrated that only participants consuming the SR formulation experienced a significant increase in muscle carnosine. Differences in the muscle carnosine response between these formulations may have practical significance for athletic populations in which small changes may have important implications on performance.

Effective bone tissue engineering is important to overcome the unmet clinical challenges as more than 1.6 million bone grafts are done annually in the United States. Successful bone tissue engineering needs minimally three critical constituents: osteoprogenitor cells, osteogenic factors, and osteoinductive/osteoconductive scaffolds. Osteogenic progenitors are derived from multipotent mesenchymal stem cells (MSCs), which can be prepared from numerous tissue sources, including adipose tissue. We previously showed that BMP9 is the most osteogenic BMP and induces robust bone formation of immortalized mouse adipose-derived MSCs entrapped in a citrate-based thermoresponsive hydrogel referred to as PPCNg. As graphene and its derivatives emerge as promising biomaterials, here we develop a novel thermosensitive and injectable hybrid material by combining graphene oxide (GO) with PPCNg (designated as GO-P) and characterize its ability to promote bone formation. We demonstrate that the thermoresponsive behavior of the hybrid material is maintained while effectively supporting MSC survival and proliferation. Furthermore, GO-P induces early bone-forming marker alkaline phosphatase (ALP) and potentiates BMP9-induced expression of osteogenic regulators and bone markers as well as angiogenic factor VEGF in MSCs. In vivo studies show BMP9-transduced MSCs entrapped in the GO-P scaffold form well-mineralized and highly vascularized trabecular bone. Thus, these results indicate that GO-P hybrid material may function as a new biocompatible, injectable scaffold with osteoinductive and osteoconductive activities for bone regeneration.