Percutaneous bone marrow concentrate and platelet products versus exercise therapy for the treatment of rotator cuff tears: a randomized controlled, crossover trial with 2-year follow-up.

BACKGROUND: Surgical repair is recommended for the treatment of high-grade partial and full thickness rotator cuff tears, although evidence shows surgery is not necessarily superior to non-surgical therapy. The purpose of this study was to compare percutaneous orthobiologic treatment to a home exercise therapy program for supraspinatus tears. METHODS: In this randomized-controlled, crossover design, participants with a torn supraspinatus tendon received either 'BMC treatment', consisting of a combination of autologous bone marrow concentrate (BMC) and platelet products, or underwent a home exercise therapy program. After three months, patients randomized to exercise therapy could crossover to receive BMC treatment if not satisfied with shoulder progression. Patient-reported outcomes of Numeric Pain Scale (NPS), Disabilities of the Arm, Shoulder, and Hand, (DASH), and a modified Single Assessment Numeric Evaluation (SANE) were collected at 1, 3, 6, 12, and 24 months. Pre- and post-treatment MRI were assessed using the Snyder Classification system. RESULTS: Fifty-one patients were enrolled and randomized to the BMC treatment group (n = 34) or the exercise therapy group (n = 17). Significantly greater improvement in median ΔDASH, ΔNPS, and SANE scores were reported by the BMC treatment group compared to the exercise therapy group (-11.7 vs -3.8, P = 0.01; -2.0 vs 0.5, P = 0.004; and 50.0 vs 0.0, P < 0.001; respectively) after three months. Patient-reported outcomes continued to progress through the study's two-year follow-up period without a serious adverse event. Of patients with both pre- and post-treatment MRIs, a majority (73%) showed evidence of healing post-BMC treatment. CONCLUSIONS: Patients reported significantly greater changes in function, pain, and overall improvement following BMC treatment compared to exercise therapy for high grade partial and full thickness supraspinatus tears. TRIAL REGISTRATION: This protocol was registered with www. CLINICALTRIALS: gov (NCT01788683; 11/02/2013).

The use of injectable orthobiologics for knee osteoarthritis: A European ESSKA-ORBIT consensus. Part 1-Blood-derived products (platelet-rich plasma).

PURPOSE: The aim of this European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) consensus is to provide recommendations based on evidence and expert opinion to improve indications, decision-making and administration-related aspects when using blood-derived orthobiologics (for simplicity indicated as PRP-platelet-rich plasma-with PRP being the most common product) for the management of knee osteoarthritis (OA). METHODS: Leading European expert clinicians and scientists were divided into a steering group, a rating group and a peer review group. The steering group prepared 28 question-statement sets divided into three sections: PRP rationale and indications, PRP preparation and characterisation and PRP protocol. The quality of the statements received grades of recommendation ranging from A (high-level scientific support) to B (scientific presumption), C (low-level scientific support) or D (expert opinion). The question-statement sets were then evaluated by the rating group, and the statements scored from 1 to 9 based on their degree of agreement with the statements produced by the steering group. Once a general consensus was reached between the steering and rating groups, the document was submitted to the peer review group who evaluated the geographic adaptability and approved the document. A final combined meeting of all the members of the consensus was held to produce the official document. RESULTS: The literature review on the use of blood-derived products for knee OA revealed that 9 of 28 questions/statements had the support of high-level scientific literature, while the other 19 were supported by a medium-low scientific quality. Three of the 28 recommendations were grade A recommendations: (1) There is enough preclinical and clinical evidence to support the use of PRP in knee OA. This recommendation was considered appropriate with a strong agreement (mean: 8). (2) Clinical evidence has shown the effectiveness of PRP in patients for mild to moderate degrees of knee OA (KL ≤ 3). This recommendation was considered appropriate with a strong agreement (mean: 8.1). (3) PRP injections have been shown to provide a longer effect in comparison to the short-term effect of CS injections. They also seem to provide a safer use profile with less potential related complications. This recommendation was considered appropriate with a very strong agreement (mean: 8.7). Six statements were grade B recommendations, 7 were grade C and 12 were grade D. The mean rating score was 8.2 ± 0.3. CONCLUSIONS: The consensus group reached a high level of agreement on all the questions/statements despite the lack of clear evidence for some questions. According to the results from this consensus group, given the large body of existing literature and expert opinions, PRP was regarded as a valid treatment option for knee OA and as a possible first-line injectable treatment option for nonoperative management of knee OA, mainly for KL grades 1-3. LEVEL OF EVIDENCE: Level II.

Staying out of trouble: FDA regulation of orthobiologics and the shoulder surgeon.

BACKGROUND: Food and Drug Administration (FDA) regulation of orthobiologics can be challenging to interpret for the nonregulatory scientist. However, understanding how regulations apply to clinical use of these orthobiologic products is critical, as there are both ethical and legal ramifications to using orthobiologics in conflict with regulations. Recent FDA guidances have attempted to clarify these issues, although questions still remain regarding nuances in regulatory applications. METHODS: FDA guidances, industry blogs, and relevant publications were searched for citations regarding recent orthobiologics and regulations. These sources were compiled into a current assessment of FDA regulations regarding the use of orthobiologics in the shoulder. RESULTS: Key to understanding these regulations is the FDA differentiation of human cellular and tissue-based products into 361 and 351 category products. Although some controversy still exists, the FDA has attempted to clarify these issues with several recent guidances. Of equal importance, the FDA has ended enforcement discretion for many biologic products in June of 2021, creating a previously tolerated class of orthobiologics that now requires an Investigational New Drug application and subsequent Biologic License Application to legally market these orthobiologics. The same surgical procedure exception was further clarified in 2017 to exempt facilities from regulatory controls when specific guidelines are met. CONCLUSIONS: This article attempts to clarify the current thinking on FDA regulations and will allow the shoulder and elbow surgeon to stay within the current bounds of ethical and legal use of these products.

Injection therapy in professional footballers.

BACKGROUND: Injection therapy offers a minimally invasive approach for symptomatic relief that allows concurrent training, limiting time loss and providing a faster recovery. However, there is a lack of scientific evidence to support it, and there are controversies about its use. The present narrative review aims to present the available scientific literature on injection therapies in professional footballers (PF), highlighting the advantages and disadvantages of its use in the most common injuries. METHODS: The authors searched and reviewed contemporary literature on injection therapies in PF in electronic databases, summarizing them in a narrative review. RESULTS: Injection therapies such as hyaluronic acid and PRP have shown an adequate safety profile that allows their use. Current evidence suggests that hyaluronic acid injections are a valid option for managing symptomatic cartilage injuries. At the same time, PRP injections have failed to prove beneficial in treating muscle injuries and should be avoided until further evidence proves the opposite. Yet, PRP may have potential use in partial ACL injuries, anterior inferior tibiofibular ligament injuries (ankle syndesmosis), and fifth metatarsal fractures and needs further study. Due to the long-term health repercussions, other injection therapies should be preferred over corticosteroids in PF. CONCLUSIONS: There is a paucity of evidence on the use and benefits of injection therapies in PF despite its extensive use among physicians. Viscosupplementation may have a role in improving symptomatic cartilage injuries. In contrast, PRP injection therapy needs further high-quality clinical trials to assess its role in PF sports injuries.

Cell-Based Therapies for Rotator Cuff Injuries: An Updated Review of the Literature.

This review focuses on non-surgical treatment options for rotator cuff injuries and highlights the potential of mesenchymal stem cells (MSCs) as a potential regenerative approach. MSCs, sourced from various tissues like bone marrow and adipose tissue, exhibit promising mechanisms in vitro, influencing tendon-related gene expression and microenvironment modulation. Animal studies support this, showcasing MSCs' ability to reduce inflammation, improve tissue remodeling, and enhance repaired tendon strength. Human trials, while varied and limited, suggest that MSCs might lower retear rates and enhance post-repair outcomes, but randomized controlled trials yield mixed results, emphasizing the necessity for standardized investigations. Ultimately, while cell-based therapies demonstrate an excellent safety profile, more rigorous clinical trials are necessary to determine their efficacy in improving patient outcomes and achieving lasting structural changes in rotator cuff injuries.

Stable Housekeeping Genes in Bone Marrow, Adipose Tissue, and Amniotic Membrane-Derived Mesenchymal Stromal Cells for Orthopedic Regenerative Medicine Approaches.

The therapeutic effect of mesenchymal stromal cells (MSCs) has been described for a variety of disorders, including those affecting musculoskeletal tissues. In this context, the literature reports several data about the regenerative effectiveness of MSCs derived from bone marrow, adipose tissue, and an amniotic membrane (BMSCs, ASCs, and hAMSCs, respectively), either when expanded or when acting as clinical-grade biologic pillars of products used at the point of care. To date, there is no evidence about the superiority of one source over the others from a clinical perspective. Therefore, a reliable characterization of the tissue-specific MSC types is mandatory to identify the most effective treatment, especially when tailored to the target disease. Because molecular characterization is a crucial parameter for cell definition, the need for reliable normalizers as housekeeping genes (HKGs) is essential. In this report, the stability levels of five commonly used HKGs (ACTB, EF1A, GAPDH, RPLP0, and TBP) were sifted into BMSCs, ASCs, and hAMSCs. Adult and fetal/neonatal MSCs showed opposite HKG stability rankings. Moreover, by analyzing MSC types side-by-side, comparison-specific HKGs emerged. The effect of less performant HKG normalization was also demonstrated in genes coding for factors potentially involved in and predicting MSC therapeutic activity for osteoarthritis as a model musculoskeletal disorder, where the choice of the most appropriate normalizer had a higher impact on the donors rather than cell populations when compared side-by-side. In conclusion, this work confirms HKG source-specificity for MSCs and suggests the need for cell-type specific normalizers for cell source or condition-tailored gene expression studies.

Treatment of anterior knee pain due to chondromalacia patellae with platelet-rich plasma and hyaluronic acid in young and middle-aged adults, a cohort study.

INTRODUCTION: Anterior knee pain commonly affects young women resulting in the declination of the quality of life. One of the possible pathologies causing this symptom is chondromalacia patellae (CMP). Although CMP is used to describe the softening of patellar articular cartilage, it remains a general descriptive term as it cannot be associated with a specific pathophysiologic mechanism. The objective of this study is to investigate the effect of injectable PRP on patients with anterior knee pain in absence of altered patellofemoral joint anatomy. METHODS: For this purpose, 43 patients of the affected population were recruited to participate in this non-randomized controlled trial, 28 patients in the injection group and 15 in the only-physiotherapy group. While patients in the experimental group received three PRP injections and one injection of hyaluronic acid (HA), comparators received the standard physical therapy regimen. The treatment choice was based on patients own decree. Patients between the ages of 18 to 50 years with anterior knee pain and positive Clarke´s sign were eligible for inclusion. Patients with evident anatomical abnormalities, chronic conditions affecting the knee and severe symptoms such as blocking, were excluded from the study. Patient related measures (PROMS) in the form of the VAS and the Kujala scores were the main outcome of interest. All outcomes were measured at baseline, and after 3 and 6 months after the treatment. RESULTS: Although an improvement was seen in both groups, a statistically significant difference favoring the injection of PRP over the physiotherapy-only group was observed (p < 0.001). The superiority of the therapeutic modality under investigation was observed at 3 and 6 months after the initial diagnosis was made. Furthermore, the results of this study revealed a significant improvement at 3 and 6 months when compared to baseline measures. The analysis of the patients age showed a negative correlation when baseline values were compared to measures at 3 and 6 months, meaning younger patients had more benefit from the treatment. DISCUSSION: The main results of this study affirm the positive effects of PRP and HA for the treatment of anterior knee pain described by previous research and the subsequent improvement of the quality of life. Relatively little information was found in the literature search regarding the therapeutic effects of PRP on anterior knee pain and chondropathies. While a previous radiologic study found no evidence regarding the effect of PRP, this study found a benefit when comparing PROMs between patient groups.

Preparing the soil: Adjusting the metabolic health of patients with chronic wounds and musculoskeletal diseases.

In recent years, systemic inflammation has emerged as a pivotal player in the development and progression of various degenerative diseases. This complex, chronic inflammatory state, often undetected, can have far-reaching consequences for the body's physiology. At the molecular level, markers such as C-reactive protein, cytokines and other inflammatory mediators serve as indicators of systemic inflammation and often act as predictors of numerous musculoskeletal diseases and even certain forms of cancer. The concept of 'meta-inflammation', specifically referring to metabolically triggered inflammation, allows healthcare professionals to understand inflammatory responses in patients with metabolic syndrome. Driven by nutrient excess and the expansion of adipose tissue, meta-inflammation is closely associated with insulin resistance, further propagating the metabolic dysfunction observed in many Western societies. Wound persistence, on the other hand, exacerbates the detrimental effects of prolonged inflammation at the local level. Acute inflammation is a beneficial and essential process for wound healing and infection control. However, when inflammation fails to resolve, it can impede the healing process, leading to chronic wounds, excessive scarring and even the activation of fibrotic pathways. This approach significantly reduces the efficacy of regenerative biological therapies. Our review focuses on the vital role of proteins, vitamins and minerals in collagen synthesis and cell proliferation for tissue healing. We also examine hormonal influences on regeneration, noting the negative effects of imbalances, and emphasize glucose regulation's importance in creating a stable environment for chronic wound healing.

Is there structural change on MRI in gluteal tendinopathy after treatment? Single outcome measure extension of an RCT.

BACKGROUND: The etiology of tendinopathy remains controversial and it is unknown whether degenerative structural changes in tendinopathies are reversible. HYPOTHESIS: There will be no structural change on magnetic resonance imaging (MRI) taken > 2-years after treatment for gluteal tendinopathy. STUDY DESIGN: Extension of a single site, double-blind, prospective randomized-controlled trial to analyze the additional outcome measure; MRI changes. METHODS: University of Melbourne ethics approval number: 1852900, trial registration: ACTRN12613000677707. Participants with gluteal tendinopathy who had previously received a leukocyte-rich platelet-rich plasma injection (LR-PRP) or a corticosteroid injection (CSI) had a post treatment MRI between at least 2-years and up to 7 years following trial completion. A blinded, senior musculoskeletal radiologist graded all de-identified MRI scans using the Melbourne Hip Score (MHIP). The primary outcome measure was the change in overall pre- and post-treatment score. RESULTS: Participants (n = 20) underwent MRI at mean time of 4.15 (SD 1.11; range 2-7) years after their initial treatment. There was no change in the overall mean MHIP score for the CSI group (Pre 4.3 (SD 2.3) Post 4.3 (SD 1.1), p = 1.00). Although there was an improvement in the LR-PRP group mean MHIP score (Pre 5.3 (SD 3.0) Post 4.77 (SD 2.5), p = 0.56) it was not statistically significant. However, in the LR-PRP intervention group, five out of nine of participants' MHIP score improved, with four of these improving by 2-4 points. CONCLUSION: The hypothesis that there would be no improvement in MHIP scores following treatment of gluteal tendinopathy was supported. Findings of improvement in the LR-PRP group at 4 years would support further studies powered to look for structural improvement. These findings suggest that structural change following treatment for tendinopathy may be possible supporting the inclusion of MRI as a core outcome for future studies. CLINICAL RELEVANCE: The study suggests that degenerative structural changes in tendons may be reversible.

Biological intra-articular augmentation for osteotomy in knee osteoarthritis: strategies and results : A systematic review of the literature from the ESSKA Orthobiologics Initiative.

PURPOSE: To assess whether there is evidence supporting the use of augmentation strategies, either cartilage surgical procedures or injective orthobiologic options, to improve the results of osteotomies in knees with osteoarthritis (OA). METHODS: A systematic review of the literature was performed on the PubMed, Web of Science and the Cochrane databases in January 2023 on osteotomies around the knee associated with augmentation strategies (either cartilage surgical procedures or injective orthobiologic options), reporting clinical, radiological, or second-look/histological outcomes at any follow-up. The methodological quality of the included studies was assessed with the Coleman Methodology Score (CMS). RESULTS: Out of the 7650 records identified from the databases, 42 articles were included for a total of 3580 patients and 3609 knees treated; 33 articles focused on surgical treatments and 9 on injective treatments performed in association with knee osteotomy. Out of the 17 comparative studies with surgical augmentation, only 1 showed a significant clinical benefit of an augmentation procedure with a regenerative approach. Overall, other studies showed no differences with reparative techniques and even detrimental outcomes with microfractures. Regarding injective procedures, viscosupplementation showed no improvement, while the use of platelet-rich plasma or cell-based products derived from both bone marrow and adipose tissue showed overall positive tissue changes which translated into a clinical benefit. The mean modified CMS score was 60.0 ± 12.1. CONCLUSION: There is no evidence to support the effectiveness of cartilage surgical treatments combined with osteotomies in terms of pain relief and functional recovery of patients affected by OA in misaligned joints. Orthobiologic injective treatments targeting the whole joint environment showed promising findings. However, overall the available literature presents a limited quality with only few heterogeneous studies investigating each treatment option. This ORBIT systematic analysis will help surgeons to choose their therapeutic strategy according to the available evidence, and to plan further and better studies to optimize biologic intra-articular osteotomy augmentation. LEVEL OF EVIDENCE: Level IV.

Mesenchymal stem cell implantation provides short-term clinical improvement and satisfactory cartilage restoration in patients with knee osteoarthritis but the evidence is limited: a systematic review performed by the early-osteoarthritis group of ESSKA-European knee associates section.

PURPOSE: Implantation of mesenchymal stem cells (MSCs) is a potential cell-based modality for cartilage repair. Currently, its clinical use largely surrounds focal cartilage defect repair and intra-articular injections in knee osteoarthritis. The MSCs' implantation efficacy as a treatment option for osteoarthritis remains contentious. This systematic review aims to evaluate studies that focused on MSCs implantation in patients with knee OA to provide a summary of this treatment option outcomes. METHODS: A systematic search was performed in PubMed (Medline), Scopus, Cinahl, and the Cochrane Library. Original studies investigating outcomes of MSCs implantations in patients with knee OA were included. Data on clinical outcomes using subjective scores, radiological outcomes, and second-look arthroscopy gradings were extracted. RESULTS: Nine studies were included in this review. In all included studies, clinical outcome scores revealed significantly improved functionality and better postoperative pain scores at 2-3 years follow-up. Improved cartilage volume and quality at the lesion site was observed in five studies that included a postoperative magnetic resonance imaging assessment and studies that performed second-look arthroscopy. No major complications or tumorigenesis occurred. Outcomes were consistent in both single MSCs implantation and concurrent HTO with MSCs implantation in cases with excessive varus deformity. CONCLUSION: According to the available literature, MSCs implantation in patients with mild to moderate knee osteoarthritis is safe and provides short-term clinical improvement and satisfactory cartilage restoration, either as a standalone procedure or combined with HTO in cases with axial deformity. However, the evidence is limited due to the high heterogeneity among studies and the insufficient number of studies including a control group and mid-term outcomes. LEVEL OF EVIDENCE: IV.

Orthobiologics as an adjunct in treatment of femoroacetabular impingement syndrome: cell-based therapies facilitate improved postoperative outcomes in the setting of acetabular chondral lesions-a systematic review.

PURPOSE: To evaluate studies utilizing orthobiologics in the management of femoroacetabular impingement syndrome (FAIS) to (1) assess the indications for usage, and (2) analyze patient-reported outcome measures (PROM) following treatment. It was hypothesized that orthobiologics would (1) be utilized for symptomatic FAIS in the setting of labral or chondral pathology, and (2) improve PROM at most recent follow-up. METHODS: The Pubmed, Ovid Medline, Cochrane, and Web of Science databases were searched for clinical studies evaluating orthobiologics [hyaluronic acid (HA), platelet-rich plasma (PRP), or cell-based therapy (CBT) for treatment of FAIS. Exclusion criteria included orthobiologics used in conjunction with cartilage transfer or scaffolding procedures and a primary indication other than FAIS. Data collection included patient demographics, indications, and baseline and most recent PROM. RESULTS: Eleven studies (one level I, four level II, four level III, and two level IV evidence) met inclusion criteria, consisting of 440 patients with mean ages ranging from 32.8 to 47 years. All 11 studies demonstrated an improvement in PROM from baseline to most-recent follow-up. Four studies administered PRP either intraoperatively or the day after surgery as an adjunct to labral repair. CBT was used intraoperatively in the setting of acetabular chondral lesions (three studies) and labral repair (one study). When comparing to a control group at most recent follow-up, three PRP cohorts demonstrated similar PROM (n.s.), while one PRP group exhibited worse visual analog pain scores (2.5 vs. 3.4, p = 0.005) and modified Harris Hip Scores (mHHS) (82.6 vs. 78.7, p = 0.049). The four CBT studies reported favorable results compared to a control group, with a significantly higher mHHS at most recent follow-up or mean improvement from baseline in Hip Outcome Score-Activities of Daily Living (p < 0.05). Three studies reported on HA, which was utilized exclusively in the nonoperative setting. CONCLUSIONS: Intraoperative PRP and CBT have been commonly reported in the setting of hip arthroscopy for labral repairs and acetabular chondral lesions, respectively. The CBT cohorts demonstrated more favorable PROM at most recent follow-up when compared to a control group, though these results should be interpreted with caution due to heterogeneity of orthobiologic preparations. LEVEL OF EVIDENCE: IV.

Orthobiologics: a review.

PURPOSE: The use of biologic materials in orthopaedics (orthobiologics) has gained significant attention over the past years. To enhance the body of the related literature, this review article is aimed at summarizing these novel biologic therapies in orthopaedics and at discussing their multiple clinical implementations and outcomes. METHODS: This review of the literature presents the methods, clinical applications, impact, cost-effectiveness, and outcomes, as well as the current indications and future perspectives of orthobiologics, namely, platelet-rich plasma, mesenchymal stem cells, bone marrow aspirate concentrate, growth factors, and tissue engineering. RESULTS: Currently available studies have used variable methods of research including biologic materials as well as patient populations and outcome measurements, therefore making comparison of studies difficult. Key features for the study and use of orthobiologics include minimal invasiveness, great healing potential, and reasonable cost as a nonoperative treatment option. Their clinical applications have been described for common orthopaedic pathologies such as osteoarthritis, articular cartilage defects, bone defects and fracture nonunions, ligament injuries, and tendinopathies. CONCLUSIONS: Orthobiologics-based therapies have shown noticeable clinical results at the short- and mid-term. It is crucial that these therapies remain effective and stable in the long term. The optimal design for a successful scaffold remains to be further determined.

Relations between Structure/Composition and Mechanics in Osteoarthritic Regenerated Articular Tissue: A Machine Learning Approach.

In the context of a large animal model of early osteoarthritis (OA) treated by orthobiologics, the purpose of this study was to reveal relations between articular tissues structure/composition and cartilage viscoelasticity. Twenty-four sheep, with induced knee OA, were treated by mesenchymal stem cells in various preparations-adipose-derived mesenchymal stem cells (ADSCs), stromal vascular fraction (SVF), and amniotic endothelial cells (AECs)-and euthanized at 3 or 6 months to evaluate the (i) biochemistry of synovial fluid; (ii) histology, immunohistochemistry, and histomorphometry of articular cartilage; and (iii) viscoelasticity of articular cartilage. After performing an initial analysis to evaluate the correlation and multicollinearity between the investigated variables, this study used machine learning (ML) models-Variable Selection Using Random Forests (VSURF) and Extreme Gradient Boosting (XGB)-to classify variables according to their importance and employ them for interpretation and prediction. The experimental setup revealed a potential relation between cartilage elastic modulus and cartilage thickness (CT), synovial fluid interleukin 6 (IL6), and prostaglandin E2 (PGE2), and between cartilage relaxation time and CT and PGE2. SVF treatment was the only limit on the deleterious OA effect on cartilage viscoelastic properties. This work provides indications to future studies aiming to highlight these and other relationships and focusing on advanced regeneration targets.

Equine Autologous Conditioned Serum and Autologous Protein Solution.

Orthobiologics are used with increasing frequency in equine musculoskeletal disease to improve the quality of the repair tissue and prevent reinjury. Autologous blood-based products, or hemoderivatives, are made by processing the patient's blood using different systems to produce a final therapeutic product. Autologous conditioned serum (ACS) and autologous protein solution (APS) are commonly used to treat joint disorders and can also be used treat tendon and ligament injuries. Hemoderivatives contain increased concentrations of anti-inflammatory and immunomodulatory cytokines, and growth factors that help direct tissue healing and repair. The specifics of ACS and APS for treatment of musculoskeletal injuries are discussed.

Introduction to Equine Biologic and Regenerative Therapies.

Regenerative medicine is defined as the process of replacing or regenerating cells, tissues, or organs to restore or establish normal function. The use of regenerative medicine in equine practice to treat injured musculoskeletal tissues with limited capacity for intrinsic healing is growing. This article provides the practitioner with a brief and basic overview of the regenerative products currently used in equine practice.

The use of platelet-rich plasma in pathologies of the foot and ankle: A comprehensive review of the recent literature.

Platelet-rich plasma (PRP) is an autologous serum containing higher concentrations of platelets and growth factors above normal blood. The process of obtaining PRP involves the extraction of blood from the patient which is then centrifuged to obtain a concentrated suspension of platelets. PRP continues to evolve as a potential treatment modality with many applications in orthopaedic surgery. The therapeutic components of PRP possess numerous theoretical regenerative properties. The present manuscript outlines how PRP is prepared, noting the tremendous variability between preparation protocols. Given the growing body of evidence examining the use of PRP in pathologies of the foot and ankle, we assess its efficacy as it relates to our field. Specifically, we evaluate the literature in the past five years regarding the role of PRP in treating plantar fasciitis, Achilles tendinopathy, insertional Achilles tendinitis, Achilles tendon ruptures, osteochondral lesions of the talus, hallux rigidus, and ankle osteoarthritis.

Patient registries in orthopedics and orthobiologic procedures: a narrative review.

There has been increasing evidence and growing popularity of orthobiologic treatments, such as platelet-rich plasma, bone marrow aspirate concentrate, and microfragmented adipose tissue. However, real-world data, including patient-reported pain and function outcomes, remains sparse for these procedures. Thus, collecting patient-reported outcome measures is important to evaluate the safety and efficacy of these treatments and hopefully improve patient care. Patient reported outcome measures can systematically be collected through patient registries. This narrative review serves to describe the data collection platforms and registries that obtain patient-reported outcome measures on orthobiologic procedures and provide a discussion on the benefits and limitations of registries. An internet search of the list of orthopedic registries available was conducted, and registries that collect patient-reported outcome measures for orthobiologic procedures were identified. Additional information regarding these various registries was collected by directly contacting these vendors. Publications from these registries, including case series, observational studies, and annual reports, were also reviewed. Providing this review will inform clinicians of a digital tool that can increase the efficiency of collecting outcome measures for orthobiologics and aid physicians in choosing a data collection platform.

Biologically Augmented Suture for Ligament Bracing Procedures Positively Affects Human Ligamentocytes and Osteoblasts In Vitro.

PURPOSE: The purpose was to evaluate the response of human ligamentocytes and osteoblasts after biological augmentation with thrombin, concentrated bone marrow aspirate (cBMA), or platelet-rich plasma (PRP) on two different types of nonresorbable flat braided suture used for ligament bracing. METHODS: Uncoated (U) and collagen-coated (C) flat braided suture material was augmented with either thrombin (T), cBMA (B), PRP (P), or a combination of these three (A), while platelet-poor plasma was used as a source for fibrin (F) in each assay. Previously cultured ligamentocytes and osteoblasts were added with a defined density and assayed after the required time period for adhesion, proliferation, and alkaline phosphatase activity. RESULTS: Biological augmentation of uncoated [(UFT, UFBT, UFA; P < .001), (UFPT; P = .017)] and collagen-coated suture (CFT, CFPT, CFBT, CFA; P < .001) led to a significantly higher ligamentocyte adhesion. Significantly higher adhesion was also observed for osteoblasts (UFT, UFPT, UFBT, UFA; P < .001; CFT, CFPT, CFBT, CFA; P < .001). Similarly, ligamentocyte proliferation was significantly higher [(UFT, UFPT, UFA; P = .009), (UFBT; P = .001), (CFT; P = .009), (CFBT; P = .001), and (CFA; P = .01)]. Osteoblasts showed significantly higher proliferation as well [(UFT, UFPT, UFA; P = .002), (UFBT; P = .001); (CFT: P = .003), and (CFPT, CFBT, CFA; P = .001)]. Augmentation with thrombin, PRP, and BMA for uncoated (UFT; P = .006, UFPT; P = .035, UFBT; P = .001) and BMA for coated suture (CFBT; P = .027) led to significantly higher alkaline phosphatase activity. CONCLUSION: Biological enhancement of suture used for ligament bracing significantly increased ligamentocyte and osteoblast adhesion and proliferation, as well as alkaline phosphatase activity of osteoblasts in an in vitro model. After biological augmentation, cellular adhesion, proliferation, and alkaline phosphatase activity changed up to 1,077%, 190%, and 78%, respectively. Furthermore, no overall superiority between uncoated or collagen-coated suture material was observed for cellular adhesion, proliferation, or alkaline phosphatase activity. CLINICAL RELEVANCE: This study provides in vitro data on a new treatment concept of biologic augmentation for acute ligamentous lesions treated with ligament bracing that has not been widely described. This concept may improve the healing of injured ligaments, in addition to providing immediate biomechanical stabilization.

Biologic Therapies for the Treatment of Knee Osteoarthritis: An Updated Systematic Review.

BACKGROUND: Use of "orthobiologics" continues to expand for patients who have knee osteoarthritis (OA). We sought to perform a systemic review of biologic therapies relative to comparative groups, including the following: (1) platelet-rich plasma (PRP); (2) bone marrow-derived mesenchymal stem cells (BMSCs); (3) adipose-derived mesenchymal stem cells (ADSCs); and (4) amniotic-derived mesenchymal stem cells (AMSCs). We assessed the following: (1) study methodologies; (2) cell preparations and formulations; (3) patient-reported outcome scores (PROMs); and (4) structural changes. METHODS: PubMed, Cochrane Library, and Embase databases were queried (2013-2021) to conduct a systematic review of biologic therapies for knee OA, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eighty-two studies were included: PRP (51); BMSC (15); ADSC (11); and AMSC (5). Study evaluations were made using the Modified Coleman Methodology Score. PROMs included the Western Ontario and McMaster Universities Arthritis Index and the Visual Analog Scale. Structural change evaluations included ultrasounds, radiographs, or magnetic resonance imaging. RESULTS: PRP comprised a majority of the studies (n = 51), most with "fair" to "good" Modified Coleman Methodology Score. Studies had variable cell preparations and formulations, with comparison study results leading to inconsistent PROMs, and structural changes. A limited number of studies were included for BMSC, ADSC, and AMSC, all with similar findings to PRP. CONCLUSION: Available literature evaluating "orthobiologics" for knee OA remain nonsuperior to comparison cohorts. Higher level studies with larger sample sizes and improved methodologies are warranted to suggest differences. Despite a growth of "orthobiologics" in clinics, this updated systematic review highlights the uncertain efficacy for use in knee OA.