Shapiro, Shane A.

Background: Platelet-rich plasma (PRP) is an emerging therapy that demonstrates potential benefits for knee osteoarthritis (OA); however, the accessibility of PRP remains limited, in part, because its use is not covered by insurance. Purpose: To identify factors contributing to health disparities in PRP treatment for knee OA using machine learning models. Study Design: Cross-sectional study; Level of evidence, 3. Methods: The authors collected data from electronic medical records at 2 upper Midwest medical centers (Mayo Clinic and Detroit Medical Center) from 2022 to 2023 encompassing demographic, socioeconomic, and clinical factors. Data collection encompassed age, sex, race, ethnicity, area deprivation index, marital status, income, rurality, insurance, employment, language, religion, treatment site, and region. Logistic regression and random forest models were applied to 3667 samples (80% training, 20% testing), comparing PRP recipients against a standard care group. Models were evaluated using 10-fold cross-validation to ensure robust performance assessment. Results: Logistic regression revealed that increased age, widowed status, lower income, rural residence, unemployment/disability, and Medicaid/Medicare insurance were associated with lower odds of receiving PRP. Upper-middle income, contracted insurance, and treatment at the Mayo-Arizona and Mayo-Florida sites were associated with higher odds. The model achieved areas under the curve of 0.83 (training set) and 0.82 (testing set). Random forest analysis identified distance to care, age, area deprivation index, income, and treatment site as top predictors, with areas under the curve of 0.92 (training) and 0.87 (testing). Conclusion: The current study demonstrated that both models discerned key barriers (income, distance to care, retirement status) and facilitators (regional differences) affecting PRP accessibility. These findings provide potential policy initiatives aimed at improving PRP access for underserved demographics, offering a quantitative blueprint to foster equitable access to regenerative therapies for knee OA.

Background Current literature has shown benefit of radial pressure wave (RPW) and focused shockwave (FSW) for management of proximal hamstring tendinopathy (PHT), although there remains a lack of consensus on treatment parameters and optimal patient positioning. Purpose The purpose of this narrative review and clinical commentary is to report what has been described for patient positioning during treatment of PHT with RPW or FSW and propose an alternative side lying approach. Methods A search was conducted of MEDLINE/PubMed and EMBASE electronic databases for studies published from January 2005 to January 2026. Key search terms included proximal hamstring tendinopathy, shockwave therapy, extracorporeal shockwave treatment, radial pressure wave, hamstring tendinosis, hamstring tendinitis, and hamstring pain. Studies were included if they evaluated RPW or FSW for the treatment of PHT. Results Six manuscripts were identified for inclusion, two randomized controlled trials (RCT), two retrospective reviews, and two case reports; a total of 217 patients (145 female, 72 male) with PHT were treated with RPW and/or FSW. One RCT provided an in-depth description of patient positioning during shockwave treatment with the patient supine, with the hip and knee flexed, compared to other manuscripts detailing clinical focusing techniques only. One case report involving a para swimmer included a figure of treatment with the patient in a prone position. Improvement in patient reported outcomes with RPW and/or FSW was noted, with one RCT showing no differences between physiotherapy compared to RPW and FSW treatment. Conclusion RPW and FSW have some evidence regarding their benefits for treatment of PHT but controlled studies are limited and no consensus on treatment protocols or patient positioning during treatment have been determined. The authors’ preferred approach in treating PHT involves having the patient side lying with the hip and knee flexed to allow patient and clinician comfort while also creating compression of the proximal hamstring about the ischial tuberosity. It remains unclear how variance in patient positioning affects patient-reported outcomes. Future studies using RPW and FSW should include documentation of patient positioning when evaluating RPW and FSW efficacy. Level of Evidence 5

Abstract Within the field of regenerative medicine for musculoskeletal regenerative medicine, orthobiologics and cellular therapies are evolving at a rapid pace. Exuberant ideas for new treatments often outpace their scientific evidence, which may create confusion for both patients and providers on what treatments are evidence based. Orthobiologics and cellular therapies are a subset of regenerative therapies focused on treatment of musculoskeletal disease. For the field of orthobiologics to progress, it is essential that musculoskeletal providers understand the necessary components for translating novel therapies from discovery into practice. In this article, we provide an overview of both the lexicon and regulatory processes related to translation of orthobiologics and cellular therapies along with a comparison of how to translate orthobiologics and related novel cellular therapies in hopes to dispel misinformation while promoting responsible advancements and ethical practices in medicine.

Objective: Orthobiologics are increasingly sought-after interventions in sports medicine for treatment of musculoskeletal injuries and conditions. Despite this trend, differences exist across sports medicine fellowship programs regarding foundational knowledge, educational curricula, and practical experience with orthobiologic therapies (eg, platelet-rich plasma, bone marrow aspirate concentrate, microfragmented adipose tissue). This represents an important educational gap for those training in sports medicine fellowships. To address this gap, an educational toolkit was envisioned with the sports medicine fellowship director and trainee in mind. Data Sources: Collective observations from physician experts in sports medicine education established the variations in curricula and expertise of graduating fellows. A literature review was conducted to source English-language peer reviewed articles from the online PubMed database. The scope of this project did not include an independent systematic analysis or statistical assessments. Main Results: An educational toolkit consisting of 12 adaptable modules was developed, each with a suggested reading list from the published literature. The modules may be rearranged to support each program's learning schedule. The information and lessons contained herein may be valuable to all healthcare providers interested in the evidence-based application of orthobiologics and insightful interpretation of related research. Conclusions: By implementing an educational toolkit, sports medicine fellowships may improve the quality of education on orthobiologics. This is intended to improve the knowledge and skill set of fellowship graduates, thus promoting the scientific, responsible use of orthobiologic interventions.

Biologic augmentation, using substances like bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP), shows promise for improving outcomes in foot and ankle surgery, particularly in high-risk patients. Historically, autologous bone graft is the benchmark due to its trifecta of osteogenic, osteoinductive, and osteoconductive properties, despite its associated donor site morbidity. Current evidence supporting orthobiologics remains fragmented and inconclusive, with a lack of high-level randomized controlled trials (RCTs). BMAC shows fusion rates comparable to autograft in some foot and ankle applications, but PRP evidence is often conflicting due to a lack of preparation standardization. The regulatory environment is complex. The Food and Drug Administration (FDA) oversees human cells and tissues (HCT/Ps) through a tiered system: high-risk §351 products (eg, cultured stem cells) require rigorous premarket approval, whereas §361 products (eg, allograft bone) have minimal oversight. BMAC and PRP often bypass this through the Same Surgical Procedure Exemption or are regulated through their processing devices, meaning the biologics themselves are not FDA-approved therapeutics. This regulatory gap and direct-to-consumer marketing necessitate meticulous informed consent, transparently discussing the lack of specific FDA approval, limited evidence, and high out-of-pocket costs. Future success depends on standardized, prospective RCTs and a collaborative “middle-ground pathway” for regulatory approval.

Abstract Objective The goal of this study was to examine if differing platelet counts in platelet‐rich plasma (PRP) formulations affected overall pain and function outcomes when compared to hyaluronic acid or placebo control saline injections. Design/Methods We conducted a systematic review and meta‐analysis (International Prospective Register of Systematic Reviews CRD42022340057) evaluating randomized controlled trials comparing injections of PRP to hyaluronic acid (HA) or saline (NS) control in patients with mild or moderate knee osteoarthritis. All studies used a validated outcome measure that examined pain, function, or overall patient global assessment. Study PRP interventions were subclassified as investigating the total number of platelets delivered in a low dose (1–5 billion total deliverable platelets), moderate dose (5–10 billion total deliverable platelets), or high dose (greater than 10 billion total deliverable platelets) injected into the joint. Results A total of 32 trials met inclusion criteria. All three PRP groups had significant improvements in validated patient‐reported outcomes when compared to HA. Both the “low” and “high” platelet count groups resulted in a moderate effect size, respectively (standardized mean difference [SMD] = .47; 95% confidence interval [CI] .05–0.89, p < .01; SMD = .68; 95% CI .26–1.09, p < .01). Only the “moderate” (SMD = 1.48; 95% CI .71–2.58 p < .01) platelet count group resulted in large effect size on validated patient‐reported outcomes. When compared to NS, all three PRP groups resulted in significant large effect sizes when examining pain reduction. Conclusions When compared to HA, PRP with platelet counts between 1 and 10 billion total deliverable platelets may result in a larger decrease in pain symptoms when compared to platelet counts greater than 10 billion at 6 months. In addition, platelet counts between 5 and 10 billion total deliverable platelets may be associated with greater improvement in functional outcomes.

Purpose To establish consensus statements via a modified Delphi process about ethics, transparency, regulation, and best practices for the use of orthobiologics in clinical practice for musculoskeletal pathology. Methods A consensus process on the regulation of orthobiologics at the provider level was conducted using a modified Delphi technique. Twenty orthopaedic surgeons, sports medicine physicians, or basic scientists participated. Each participant was a Biologic Association member organization representative and asked to participate because of their active interest in the field of orthobiologics. Levels of consensus were delineated according to the number of votes for each statement: no consensus, <80%; consensus, 80% to 89%; strong consensus, 90% to 99%; unanimous, 100%. Results The 26 consensus statements on orthobiologics resulted in 14 achieving unanimous consensus, 8 achieving strong consensus, 3 achieving consensus, and 1 did not achieve consensus. Overall, 85% of the statements reached either a unanimous or strong consensus. Of the statements regarding communication and transparency, 9 reached unanimous consensus, including information to convey and helpful tools to describe current orthobiologics, persistent misinformation, use of the word “stem cells,” “off‐label” use, and problems with the present regulatory environment. Five statements discussing the regulation of novel orthobiologics achieved unanimous consensus. These statements highlighted research regulation, safety, and suggested improvements to regulatory issues. The statement that did not achieve any consensus was on the regulatory processes that should be in place by an institution providing novel orthobiologic treatments. No statement reached a unanimous agreement on cost or ethical considerations. Conclusions This study successfully identified key consensus statements emphasizing the importance of ethics, transparency, and regulation in the use of orthobiologics, with 85% of statements reaching unanimous or strong consensus. These findings underscore the need for standardized communication, improved regulatory frameworks, and enhanced safety measures while highlighting persistent challenges in addressing cost and ethical considerations. Level of Evidence Level V, expert opinion.

Abstract Background: Chronic dry eye disease (CDED) is a condition of the ocular surface that causes discomfort, visual disturbance, conjunctival injection, and photophobia. A debilitating form of CDED in patients undergoing allogeneic bone marrow transplant results from ocular graft versus host disease (oGVHD). Autologous serum eye drops (ASED) have beneficial effects on the ocular surface. The aim of this study is to compare improvements in symptoms and function in a cohort of CDED patients with ocular GVHD treated with ASED and a cohort of CDED without GVHD (non-GVHD). We additionally report on some of the biologic characteristics of one specific ASED formulation. Materials and Methods: A total of 71 patients seen in a multi-specialty ophthalmology practice in a university hospital setting receiving ASEDs underwent ocular surface disease index (OSDI) and visual function questionnaire measurements at baseline, 3 months, and 6 months. Twenty-four ASED samples were studied for biomarkers. Results: Compared to baseline, OSDI scores significantly decreased after 3 and 6 months of ASED treatment in both oGVHD and non-GVHD CDED groups. Additionally, visual function questionnaire-25 (VFQ-25) subscales (ocular pain, distance activity, driving, role difficulties, dependency, and mental health) were significantly improved at 3 months and 6 months, and social functioning was improved at 6 months. The majority of patients in both groups had severe disease. Improvements in patient-reported outcomes were greater in the oGHD CDED group than in the non-GVHD CDED group There were no reported complications. Conclusion: ASED is safe and effective in patients with CDED due to oGVHD and non-GVHD. Those with oGVHD had greater improvements. These findings potentiate the wider adoption of this therapy in CDED patients and warrant additional studies into the biochemical makeup of ASED.

Background: The regenerative properties of platelet growth factors make platelet-rich-plasma (PRP) an attractive modality for treatment of aging skin. The main objective of this study was to determine efficacy and safety of PRP injections and microneedling compared with saline injections in women with aging skin of the face. Methods: In this prospective, randomized clinical trial, 18 women with facial aging were randomized to receive either PRP injections to the unilateral face and saline injections to the contralateral side, or vice versa. Microneedling was performed after injections on the entire face. Physician assessment, photographs, and treatment satisfaction questionnaires were used for outcome assessment at baseline and 16- and 24-week follow-ups. Results: There was no evidence of improvement and suggestion of worsening in skin laxity and rhytides from baseline to weeks 4, 16, and 24 for PRP and saline (all P ≤ 0.004) and no notable difference in skin roughness between baseline and follow-up time points for PRP or saline (all P ≥ 0.19). The degree of change in skin laxity, rhytides, and skin roughness from baseline to follow-up time points was similar for PRP and saline. All patients experienced some degree of pain/discomfort and burning/stinging sensation at treatment weeks 4, 8, and 12 for both saline and PRP. Conclusions: PRP injections did not seem to be effective for treatment of aging skin of the face in women, with no notable macroscopic improvement in appearance when compared with baseline or saline injections. Advanced age of study participants (>45 years) and less-sensitive methods of evaluation may be potential contributing factors to the lack of detected response.