Angiogenesis and Tissue Repair Depend on Platelet Dosing and Bioformulation Strategies Following Orthobiological Platelet-Rich Plasma Procedures: A Narrative Review.

Angiogenesis is the formation of new blood vessel from existing vessels and is a critical first step in tissue repair following chronic disturbances in healing and degenerative tissues. Chronic pathoanatomic tissues are characterized by a high number of inflammatory cells; an overexpression of inflammatory mediators; such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1); the presence of mast cells, T cells, reactive oxygen species, and matrix metalloproteinases; and a decreased angiogenic capacity. Multiple studies have demonstrated that autologous orthobiological cellular preparations (e.g., platelet-rich plasma (PRP)) improve tissue repair and regenerate tissues. There are many PRP devices on the market. Unfortunately, they differ greatly in platelet numbers, cellular composition, and bioformulation. PRP is a platelet concentrate consisting of a high concentration of platelets, with or without certain leukocytes, platelet-derived growth factors (PGFs), cytokines, molecules, and signaling cells. Several PRP products have immunomodulatory capacities that can influence resident cells in a diseased microenvironment, inducing tissue repair or regeneration. Generally, PRP is a blood-derived product, regardless of its platelet number and bioformulation, and the literature indicates both positive and negative patient treatment outcomes. Strangely, the literature does not designate specific PRP preparation qualifications that can potentially contribute to tissue repair. Moreover, the literature scarcely addresses the impact of platelets and leukocytes in PRP on (neo)angiogenesis, other than a general one-size-fits-all statement that "PRP has angiogenic capabilities". Here, we review the cellular composition of all PRP constituents, including leukocytes, and describe the importance of platelet dosing and bioformulation strategies in orthobiological applications to initiate angiogenic pathways that re-establish microvasculature networks, facilitating the supply of oxygen and nutrients to impaired tissues.

Protocols and Techniques for Orthobiologic Procedures.

Many procedural techniques have been described and used for orthobiologics procedures with little research on the ideal technique. This section outlines the commonly used materials and techniques from start to finish for these procedures. Post-procedure pain is common during and after many of these injections, and local and regional anesthesia during these procedures is discussed. Accuracy and safety of tendon, ligament, cartilage, intra-osseous, and spinal orthobiologic procedures are improved with the utilization of image guidance.

Orthobiologic Treatment of Ligament Injuries.

Ligament injuries are common causes of joint pain, dysfunction, and disability resulting in disruption of joint homeostasis. Ligament injuries have historically been treated surgically. The autologous orthobiologic preparation used for treatment can influence the varying results reported. Therefore, to truly understand and compare results of these powerful therapies, reporting standardization, such as harvesting techniques, concentration techniques, quantification of the delivered product (platelets, progenitor cells), formulations (leukocyte content), number of injections performed, activation, injection technique (guided vs unguided), in addition to the post treatment rehabilitation process, are all important and necessary to evaluate and compare efficacy of future studies.

Clinical Rationale and Rehabilitation Guidelines for Post Biologic Therapy.

The use of orthobiologic modalities such as platelet-rich plasma in orthopedics and sports medicine to deliver high concentrations of naturally occurring biologically active growth factors and proteins to the site of injury is very promising and continues to evolve. Early protection and tissue-specific progressive loading are critical components to successful outcomes following orthobiologic intervention. Each tissue heals and responds differently. Ligament, tendon, muscle, and articular cartilage each have unique healing properties that require tissue-specific loading. The authors have found using a criteria-based loading and exercise progression guided by dynamic imaging when appropriate to further advance the goal-oriented rehabilitation program. Each patient and injured tissue are unique and require specific intervention and rehabilitation.

Regional Anesthesia for Orthobiologic Procedures.

Peripheral nerve blocks (PNB) can lessen procedural pain and eliminate the known detrimental effects of our local anesthetics on our orthobiologic target tissues. Local nerve damage and local anesthetic systemic toxicity are risks of PNBs that can be minimized with meticulous injection technique and an understanding of why these complications can occur. Herein, several PNB techniques are described in an effort to enhance procedural safety, efficacy, and comfort.

Modifying Orthobiological PRP Therapies Are Imperative for the Advancement of Treatment Outcomes in Musculoskeletal Pathologies.

Autologous biological cellular preparations have materialized as a growing area of medical advancement in interventional (orthopedic) practices and surgical interventions to provide an optimal tissue healing environment, particularly in tissues where standard healing is disrupted and repair and ultimately restoration of function is at risk. These cellular therapies are often referred to as orthobiologics and are derived from patient's own tissues to prepare point of care platelet-rich plasma (PRP), bone marrow concentrate (BMC), and adipose tissue concentrate (ATC). Orthobiological preparations are biological materials comprised of a wide variety of cell populations, cytokines, growth factors, molecules, and signaling cells. They can modulate and influence many other resident cells after they have been administered in specific diseased microenvironments. Jointly, the various orthobiological cell preparations are proficient to counteract persistent inflammation, respond to catabolic reactions, and reinstate tissue homeostasis. Ultimately, precisely delivered orthobiologics with a proper dose and bioformulation will contribute to tissue repair. Progress has been made in understanding orthobiological technologies where the safety and relatively easy manipulation of orthobiological treatment tools has been demonstrated in clinical applications. Although more positive than negative patient outcome results have been registered in the literature, definitive and accepted standards to prepare specific cellular orthobiologics are still lacking. To promote significant and consistent clinical outcomes, we will present a review of methods for implementing dosing strategies, using bioformulations tailored to the pathoanatomic process of the tissue, and adopting variable preparation and injection volume policies. By optimizing the dose and specificity of orthobiologics, local cellular synergistic behavior will increase, potentially leading to better pain killing effects, effective immunomodulation, control of inflammation, and (neo) angiogenesis, ultimately contributing to functionally restored body movement patterns.

Autologous thrombin preparations: Biocompatibility and growth factor release.

Platelet-rich plasma (PRP) has been investigated to promote wound healing in a variety of tissues. Thrombin, another essential component of wound healing, is sometimes combined with PRP to generate a fibrin clot in order to retain the sample at the delivery site and to stimulate growth factor release. Using a fully autologous approach, autologous serum (AS) with thrombin activity can be prepared using a one-step procedure by supplementing with ethanol (E+ AS) to prolong room temperature stability or prepared ethanol free (E- AS) by utilizing a two-step procedure to prolong stability. The objective of this study was to evaluate potential wound healing mechanisms of these two preparations using commercially available devices. A variety of tests were conducted to assess biocompatibility and growth factor release from PRP at various ratios. It was found that E- AS contained greater leukocyte viability in the product (97.1 ± 2.0% compared to 41.8 ± 11.5%), supported greater bone marrow mesenchymal stem cell proliferation (3.7× vs 0.8× at a 1:4 ratio and 3.6× vs 1.6× at a 1:10 ratio), and stimulated release of growth factors and cytokines from PRP to a greater extent than E+ AS. Of the 36 growth factors and cytokines evaluated, release of 27 of them were significantly reduced by the presence of ethanol in at least one of the tested configurations. It is concluded that the high concentrations of ethanol needed to stabilize point of care autologous thrombin preparations could be detrimental to normal wound healing processes.

Treatment of partial ulnar collateral ligament tears in the elbow with platelet-rich plasma.

BACKGROUND: Studies have demonstrated the potential of platelet-rich plasma (PRP) to heal damaged tissue. To date, there are no published reports of clinical outcomes of partial ulnar collateral ligament (UCL) tears of the elbow treated with PRP. HYPOTHESIS: Platelet-rich plasma will promote the healing of partial UCL tears and allow a return to play. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Thirty-four athletes with a partial-thickness UCL tear confirmed on magnetic resonance imaging were prospectively followed. All patients had failed at least 2 months of nonoperative treatment and an attempt to return to play. Baseline questionnaires, including the Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow (KJOC) and Disabilities of the Arm, Shoulder and Hand (DASH) measures, were completed by each patient before injection. Baseline ultrasound measurement of the humeral-ulnar joint space was assessed with 10 lb of valgus stress on the elbow. Each patient received a single type 1A PRP injection at the UCL under ultrasound guidance. The same treating physician at a single institution performed all injections with the same PRP preparation used. Patients completed a course of guided physical therapy and were allowed to return to play based on their symptoms and physical examination findings. Outcome scores, including KJOC and DASH scores, were collected after return to play and were compared with baseline scores. Ultrasound measurements were collected at final follow-up and compared with preinjection values. RESULTS: At an average follow-up of 70 weeks (range, 11-117 weeks), 30 of 34 athletes (88%) had returned to the same level of play without any complaints. The average time to return to play was 12 weeks (range, 10-15 weeks). The average KJOC score improved from 46 to 93 (P < .0001). The average DASH score improved from 21 to 1 (P < .0001). The sports module of the DASH questionnaire improved from 69 to 3 (P < .0001). Medial elbow joint space opening with valgus stress decreased from 28 to 20 mm at final follow-up (P < .0001). The difference in medial elbow joint space opening (stressed vs nonstressed) decreased from 7 to 2.5 mm at final follow-up (P < .0001). One player had persistent UCL insufficiency and underwent ligament reconstruction at 31 weeks after injection. CONCLUSION: The results of this study indicate that PRP is an effective option to successfully treat partial UCL tears of the elbow in athletes.

Clinical and magnetic resonance imaging findings associated with Little League elbow.

BACKGROUND: Valgus overload in the skeletally immature elbow can lead to medial epicondyle apophysitis, or Little League elbow. The skeletal manifestations have been well described through radiographic studies. The involvement of surrounding structures, including the ulnar collateral ligament, remains unclear. The purpose of this study is to better characterize the involvement and relationship of medial elbow structures in Little League elbow through magnetic resonance (MR) imaging. METHODS: Institutional review board approval was obtained. Nine Little Leaguers, 8 to 13 years, with clinical diagnosis of Little League elbow were enrolled. Play history questionnaire (including age, position, pitching history, duration of symptoms, and Kerlan Jobe Orthopedic Clinic shoulder elbow score), clinical examination, radiograph, and MRI of both elbows were obtained for analysis. Evaluation of radiographs and MRIs were performed by 2 radiologists blinded to clinical findings. RESULTS: A majority of the players reported compliance with pitch count recommendations. Four out of 9 players, however, were throwing breaking pitches at an average age of 11 years. Radiographic abnormalities were present in 4 players. MRI abnormalities were present in 6 players. All patients demonstrated normal ulnar collateral ligament (UCL) on MRI. The distance from UCL origin to the medial epicondyle physis were measured in both injured and healthy elbows. No significant differences were found. This distance ranged from 0 to 4 mm. CONCLUSIONS: MRI of Little League elbow demonstrated more abnormalities compared with radiographs. The increased number of findings, however, does not change clinical management. MR evaluation of the ulnar collateral ligament demonstrates no role for reconstruction in Little League elbow. In addition, given the close proximity of the ligament to the physis, any surgical procedure involving the UCL origin should be performed with caution. LEVEL III: Diagnostic study.

Injury patterns in professional arena football.

BACKGROUND: No studies to date have evaluated the injury patterns in professional arena football. The purpose of this study is to describe the characteristics of general injury patterns in the Arena Football League. HYPOTHESES: (1) Game injury rates are higher than are practice injury rates, (2) a small number of injuries are related to collision with the boards, and (3) athletes playing on both offense and defense have higher injury rates than do athletes playing either offense or defense alone. STUDY DESIGN: Descriptive epidemiology study. METHODS: A retrospective review of injury data including 1199 injuries over a 4-year period from February 2002 to December 2005, inclusive of preseason and postseason practices and competition, was conducted. Data regarding the injured body part, position of the player, nature of injury, mechanism of injury, missed playing time, playing surface, and when the injury occurred were collected and analyzed. RESULTS: Injury rates during practice were 14.6 injuries per 1000 exposures and game injury rates were 111.3 per 1000 exposures. Few recorded injuries (2.2%) involved a collision with the sideline boards. CONCLUSION: Game injury rates are higher than are practice injury rates. Athletes playing on both offense and defense did not have higher injury rates in games than did athletes playing either offense or defense. The sideline boards used in the Arena Football League did not appear to contribute dramatically to the injury rates. Despite the differences between arena and stadium football, Arena Football League injury patterns are similar to published collegiate football injury patterns.