PRP modulates the inflammatory and catabolic environment through a locally applied concentrate of platelets, leukocytes, and growth factors. Clinically, PRP has been shown to be possibly a viable treatment adjuvant for a variety of inflammatory and degenerative conditions. Recent efforts have focused on optimizing delivery methods that enable platelets to slowly degranulate their biological constituents, which may promote healing and improve OA symptoms for a longer duration. There are various factors that affect the progression of OA within joints, including inhibition of inflammatory cytokines and altering the level of enzymatic expression. PRP therapy aims to mediate inflammatory and catabolic factors in a degenerative environment through the secretion of anti-inflammatory factors and chemotaxic effects. There are a growing number of studies that have demonstrated the clinical benefit of PRP for non-operative management of OA. Additional randomized controlled trials with long-term follow-up are needed in order to validate PRP's therapeutic efficacy in this setting. Additionally, continued basic research along with well-designed pre-clinical studies and reporting standards are necessary in order to clarify the effectiveness of PRP for cartilage repair and regeneration for future clinical applications.

Background: Platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are orthobiologic therapies with numerous growth factors and other bioactive molecules. Before the clinical utility of PRP and BMC is optimized as a combined therapy or monotherapy, an improved understanding of the components and respective concentrations is necessary. Purpose: To prospectively measure and compare anabolic, anti-inflammatory, and proinflammatory growth factors, cytokines, and chemokines in bone marrow aspirate (BMA), BMC, whole blood, leukocyte-poor PRP (LP-PRP), and leukocyte-rich PRP (LR-PRP) from samples collected and processed concurrently on the same day from patients presenting for elective knee surgery. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients presenting for elective knee surgery were prospectively enrolled over a 3-week period. Whole blood from peripheral venous draw and BMA from the posterior iliac crest were immediately processed via centrifugation and manual extraction methods to prepare LR-PRP, LP-PRP, and BMC samples, respectively. BMA, BMC, whole blood, LR-PRP, and LP-PRP samples were immediately assayed and analyzed to measure protein concentrations. Results: BMC had a significantly higher interleukin 1 receptor antagonist (IL-1Ra) concentration than all other preparations (all P < .0009). LR-PRP also had a significantly higher IL-1Ra concentration than LP-PRP ( P = .0006). There were no significant differences in IL-1Ra concentration based on age, sex, body mass index, or chronicity of injury in all preparations. LR-PRP had significantly higher concentrations of platelet-derived growth factor AA (PDGF-AA) and PDGF-AB/BB than all other preparations (all P < .0006). LR-PRP also had significantly higher concentrations of matrix metalloproteinase 1 (MMP-1) and soluble CD40 ligand than all other preparations (all P < .004). LP-PRP had significantly higher concentrations of MMPs, namely MMP-2, MMP-3, and MMP-12, than all other preparations (all P < .007). Conclusion: BMC is a clinically relevant source of anti-inflammatory biologic therapy that may be more effective in treating osteoarthritis and for use as an intra-articular biologic source for augmented healing in the postsurgical inflammatory and healing phases, owing to its significantly higher concentration of IL-1Ra as compared with LR-PRP and LP-PRP. Additionally, LR-PRP had a significantly higher concentration of IL-1Ra than LP-PRP. In cases where increased vascularity and healing are desired for pathological or injured tissues, including muscle and tendon, LR-PRP may be optimal given its higher overall concentrations of PDGF, TGF-β, EGF, VEGF, and soluble CD40 ligand.

Musculoskeletal injuries that disrupt the structure and function of diarthrodial joints can cause permanent biomechanical alterations and lead to a more severe, chronic condition. Despite advancements that have been made to restore tissue function and delay the need for joint replacement, there are currently no disease-modifying therapies for osteoarthritis (OA). To reduce the risk of OA, innovative preventive medicine approaches have been developed over the last decade to treat the underlying pathology. Several biological approaches are promising treatment modalities for various stages of OA owing to their minimally invasive nature and actively dynamic physiological mechanisms that attenuate tissue degradation and inflammatory responses. Individualized growth factor and cytokine therapies, tissue-engineered biomaterials, and cell-based therapies have revolutionary potential for orthopedic applications; however, the paucity of standardization and categorization of biological components and their counterparts has made it difficult to determine their clinical and biological efficacy. Cell-based therapies and tissue-engineered biologics have become lucrative in sports medicine and orthopedics; nonetheless, there is a continued effort to produce a biological treatment modality tailored to target intra-articular structures that recapitulates tissue function. Advanced development of these biological treatment modalities will potentially optimize tissue healing, regeneration, and joint preservation strategies. Therefore, the purpose of this paper is to review current concepts on several biological treatment approaches for OA.

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Objectives: Autologous platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are orthobiologic therapies with numerous growth factors and cytokines. Mesenchymal stem cells (MSCs) are also present in BMC; however, comprise a very limited component of the available monocytes. Other clinically relevant factors and cytokines, including interleukin-1 receptor antagonist (IL-1Ra), are implicated in the anti-inflammatory and regenerative processes. Prior to optimizing the clinical utility of PRP and BMC as a combined or monotherapy, an improved understanding of the components and respective concentrations is necessary. The purpose of this study was to prospectively measure and compare anabolic, catabolic, anti-inflammatory and pro-inflammatory factors, proteins and cytokines present in bone marrow aspirate (BMA), BMC, whole blood, leukocyte poor (LP)-PRP and leukocyte rich (LR)-PRP from samples collected and processed concurrently from patients presenting for elective knee surgery. Methods: A total of 31 patients presenting for elective knee surgery were prospectively enrolled over a three-week period. Whole blood from peripheral venous draw and BMA from the posterior iliac crest were immediately processed using centrifugation and manual extraction methods to create LR- and LP-PRP and BMC, respectively. BMA, BMC, whole blood, LR-PRP and LP-PRP samples were immediately assayed and analyzed to measure factor and cytokine concentrations. We strictly adhered to the minimum reporting requirements for biological outcomes (MIBO). An a priori power and sample size calculation was performed. We conservatively assumed a Bonferroni correction among all 10 pairwise comparisons, two-tailed testing, and an overall alpha level of 0.05. Eighteen subjects was sufficient to detect this magnitude of effect size with 80% statistical power. Results: BMC had a significantly higher IL-1Ra concentration than all other preparations (all p < 0.0009, Figure 1). LR-PRP had a significantly higher IL-1Ra concentration than LP-PRP (p = 0.0006). There were no significant differences in IL-1Ra concentration based on age, gender, body mass index or chronicity of injury among all preparations (Table 1). BMC had significantly higher concentrations of leukocytes and monocytes compared to the other biologic preparations including LR-PRP. LP-PRP had significantly higher concentrations of matrix metalloproteinase (MMP)-2, MMP-3 and MMP-12 than all other preparations (all p < 0.007), while BMC had a significantly lower concentration of MMP-2 than all other preparations. LR-PRP had significantly higher concentrations of MMP-1, serum soluble CD40 ligand (sCD40 L), platelet derived growth factor (PDGF)-AA and PDGF-AB/BB than all other preparations (all p < 0.004). Conclusion: BMC is a clinically relevant source of anti-inflammatory biologic therapy that may be more effective in treating osteoarthritis and for use as an intra-articular biologic for augmented healing in the post-surgical inflammatory and healing phases due to its significantly higher concentration of IL-1Ra compared to LR-PRP and LP-PRP. Additionally, LR-PRP had a significantly higher concentration of IL-1Ra than LP-PRP. In cases where increased vascularity and healing are desired for pathological or injured tissues including muscle and tendon, LR-PRP may be optimal due to its higher overall concentrations of PDGF, TGF-β, EGF, VEGF, and sCD40 L. [Figure: see text][Table: see text]

Background: The therapeutic efficacy of orthobiologic therapies for rotator cuff repair is difficult to evaluate owing to reporting inconsistences. In response, the Minimum Information for Studies Evaluating Biologics in Orthopaedics (MIBO) guidelines were developed to ensure standard reporting on orthobiologic therapies. Purpose: To systematically review clinical studies evaluating platelet-rich plasma (PRP) for full-thickness rotator cuff repair and adherence to MIBO guidelines. Study Design: Scoping review; Level of evidence, 4. Methods: A search was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using PubMed, EMBASE, and the Cochrane Library databases. Inclusion criteria were clinical studies reporting on rotator cuff tears (≥1 cm) surgically repaired with PRP. Patient demographics, biologic intervention, and adherence to the MIBO guidelines were systematically reviewed. Results: A total of 19 studies (1005 patients) were included in this review. Across all studies, 58.5% of the MIBO checklist items for PRP were reported. Out of 47 checklist items, 19 were reported in over 85% of studies, whereas 22 were reported in less than half of studies. Details of whole-blood processing and characteristics, as well as PRP processing and characteristics, were reported inconsistently, and no study provided adequate information to enable the precise replication of preparation protocols for PRP. Conclusion: This systematic review highlights the current reporting deficiencies within the scientific literature of important variables for evaluating PRP for full-thickness rotator cuff repair. There was widespread variability among published studies that evaluate PRP for this application and, more specifically, studies were limited by inconsistent universal reporting of whole-blood and PRP processing and postprocessing characteristics. To improve our understanding of biologic efficacy and to promote repeatability, stricter adherence to the MIBO guidelines is necessary. We propose that the checklist limitations be addressed and that modification of the MIBO guidelines be considered to improve the reporting of individual components within certain categories.

Biological augmentation and therapeutics are being increasingly used in musculoskeletal and orthopaedic care. Platelet-rich plasma (PRP) is produced from centrifugation of peripheral blood, a process that concentrates platelets within autologous plasma. The process of PRP preparation is fundamental in controlling the contents, and it influences its therapeutic potential. Platelets contain alpha granules that store and release a variety of growth factors and other proteins that may augment the healing environment; PRP also has the added benefit of promoting postsurgical hemostasis. The purpose of this report was to detail our institutional preparation protocol and method of administration of PRP during hip arthroscopy.

Recent efforts have focused on customizing orthobiologics, such as platelet-rich plasma (PRP) and bone marrow concentrate (BMC), to improve tissue repair. We hypothesized that oral losartan (a TGF-β1 blocker with anti-fibrotic properties) could decrease TGF-β1 levels in leukocyte-poor PRP (LP-PRP) and fibrocytes in BMC. Ten rabbits were randomized into two groups (N = 5/group): osteochondral defect + microfracture (control, group 1) and osteochondral defect + microfracture + losartan (losartan, group 2). For group 2, a dose of 10mg/kg/day of losartan was administrated orally for 12 weeks post-operatively. After 12 weeks, whole blood (WB) and bone marrow aspirate (BMA) samples were collected to process LP-PRP and BMC. TGF-β1 concentrations were measured in WB and LP-PRP with multiplex immunoassay. BMC cell populations were analyzed by flow cytometry with CD31, CD44, CD45, CD34, CD146 and CD90 antibodies. There was no significant difference in TGF-β1 levels between the losartan and control group in WB or LP-PRP. In BMC, the percentage of CD31+ cells (endothelial cells) in the losartan group was significantly higher than the control group (p = 0.008), while the percentage of CD45+ cells (hematopoietic cells-fibrocytes) in the losartan group was significantly lower than the control group (p = 0.03).