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. Platelet-rich plasma will promote the healing of partial UCL tears and allow a return to play. Case series; Level of evidence, 4. 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. 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. The results of this study indicate that PRP is an effective option to successfully treat partial UCL tears of the elbow in athletes.

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.

Autologous platelet-rich plasma (PRP) preparations are prepared at the point of care. Centrifugation cellular density separation sequesters a fresh unit of blood into three main fractions: a platelet-poor plasma (PPP) fraction, a stratum rich in platelets (platelet concentrate), and variable leukocyte bioformulation and erythrocyte fractions. The employment of autologous platelet concentrates facilitates the biological potential to accelerate and support numerous cellular activities that can lead to tissue repair, tissue regeneration, wound healing, and, ultimately, functional and structural repair. Normally, after PRP preparation, the PPP fraction is discarded. One of the less well-known but equally important features of PPP is that particular growth factors (GFs) are not abundantly present in PRP, as they reside outside of the platelet alpha granules. Precisely, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are mainly present in the PPP fraction. In addition to their roles as angiogenesis activators, these plasma-based GFs are also known to inhibit inflammation and fibrosis, and they promote keratinocyte migration and support tissue repair and wound healing. Additionally, PPP is known for the presence of exosomes and other macrovesicles, exerting cell–cell communication and cell signaling. Newly developed ultrafiltration technologies incorporate PPP processing methods by eliminating, in a fast and efficient manner, plasma water, cytokines, molecules, and plasma proteins with a molecular mass (weight) less than the pore size of the fibers. Consequently, a viable and viscous protein concentrate of functional total proteins, like fibrinogen, albumin, and alpha-2-macroglobulin is created. Consolidating a small volume of high platelet concentrate with a small volume of highly concentrated protein-rich PPP creates a protein-rich, platelet-rich plasma (PR-PRP) biological preparation. After the activation of proteins, mainly fibrinogen, the PR-PRP matrix retains and facilitates interactions between invading resident cells, like macrophages, fibroblast, and mesenchymal stem cells (MSCs), as well as the embedded concentrated PRP cells and molecules. The administered PR-PRP biologic will ultimately undergo fibrinolysis, leading to a sustained release of concentrated cells and molecules that have been retained in the PR-PRP matrix until the matrix is dissolved. We will discuss the unique biological and tissue reparative and regenerative properties of the PR-PRP matrix.

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.

Angiogenesis is new blood vessel formation 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, 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]) im-prove 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 re-generation. 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 re-pair. 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.

Autologous platelet-rich plasma (PRP) preparations are prepared at point of care. Centrifugation cellular density separation sequesters a fresh unit of blood into three main fractions: a platelet-poor plasma (PPP) fraction, a stratum rich in platelets (platelet concentrate) and, bioformulation dependent, also leukocyte and erythrocyte fractions. The employment of autologous platelet concentrates facilitates the biological potential to accelerate and support in numerous cellular activities that can lead to tissue repair, tissue regeneration, wound healing, and ultimately functional structural repair. Normally, after PRP preparation the PPP fraction is discarded. One of the less well known, but equally important features of PPP is that particular growth factors (GFs) are not abundantly present in PRP, as they reside outside the platelet alpha granules. Precisely, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are mainly present in the PPP fraction. In addition to their roles as angiogenesis activators, these plasma-based GFs are also known to inhibit inflammation, fibrosis, and they promote keratinocyte migration and support in tissue repair and wound healing. Additionally, PPP is known for the presence of exosomes and other macrovesicles, exerting cell-cell communication and cell signaling. Newly developed ultrafiltration technologies incorporate PPP processing methods by eliminating in a fast and efficient manner plasma water, cytokines, molecules, and plasma proteins with a molecular mass (weight) less than the pore size of the fibers. Consequently, a viable and viscous protein concentrate of functional, total proteins, like fibrinogen, albumin, and alpha-2-macroglobulin is created. Consolidating a small volume of high platelet concentrate with a small volume of highly concentrated protein-rich PPP creates a protein rich platelet concentrate (PRPC) biological preparation. After the activation of proteins, mainly fibrinogen, the PRPC matrix retains and facilitates interactions between invading resident cells, like macrophages, fibroblast, and mesenchymal stem cells (MSCs), and the embedded concentrated PRP cells and molecules. The administered PRPC biologic will ultimately undergo fibrinolysis, leading to a sustained release of concentrated cells and molecules that have been retained in the PRPC matrix until the matrix is dissolved. We will discuss the unique biological and tissue reparative and regenerative properties of PRPC matrix.