CARXXX10.1177/1947603519876329CartilageHede et al. 876329research-article2019 Clinical Research Article CARTILAGE 1 –11 Combined Bone Marrow Aspirate and © The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions Platelet-Rich Plasma for Cartilage DOhttps://doi.org/10.1177/1947603519876329I: 10.1177/1947603519876329 Repair: Two-Year Clinical Results journals.sagepub.com/home/CAR Kris Hede1 , Bjørn B. Christensen1, Jonas Jensen2, Casper B. Foldager1,3, and Martin Lind3 Abstract Purpose. To evaluate the clinical and biological outcome of combined bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) on a collagen scaffold for treating cartilage lesions in the knee. Methods and Materials. Ten patients (mean age 29.4 years, range 18-36) suffering from large full-thickness cartilage in the knee were treated with BMAC and PRP from January 2015 to December 2016. In a 1-step procedure autologous BMAC and PRP was seeded onto a collagen scaffold and sutured into the debrided defect. Patients were evaluated by clinical outcome scores (IKDC [International Knee Documentation Committee Subjective Knee Form], KOOS [Knee Injury and Osteoarthritis Outcome Score], and pain score using the Numeric Rating Scale [NRS]) preoperatively, after 3 months, and after 1 and 2 years. Second-look arthroscopies were performed (n = 7) with biopsies of the repair tissue for histology. All patients had magnetic resonance imaging (MRI) preoperatively, after 1 year, and after 2 to 3.5 years with MOCART (magnetic resonance observation of cartilage repair tissue) scores evaluating cartilage repair. Results. After 1 year significant improvements were found in IKDC, KOOS symptoms, KOOS ADL (Activities of Daily Living), KOOS QOL (Quality of Life), and pain at activity. At the latest follow-up significant improvements were seen in IKDC, KOOS symptoms, KOOS QOL, pain at rest, and pain at activity. MRI MOCART score for cartilage repair improved significantly from baseline to 1-year follow-up. Histomorphometry of repair tissue demonstrated a mixture of fibrous tissue (58%) and fibrocartilage (40%). Conclusion. Treatment of cartilage injuries using combined BMAC and PRP improved subjective clinical outcome scores and pain scores at 1 and 2 years postoperatively. MRI and histology indicated repair tissue inferior to the native hyaline cartilage. Keywords articular cartilage, knee, BMAC, PRP, clinical Introduction great interest in developing new 1-step procedures. The use of bone marrow aspirate concentrate (BMAC) obtained Articular cartilage repair is biologically challenging due to and isolated intraoperatively may be an attractive 1-step its highly complex, avascular, alymphatic, and aneural method for cartilage repair. BMAC can be used as a cell nature. Cell-based repair techniques with cultured chondro- source in combination with a scaffold as alternative to cytes (autologous chondrocyte implantation [ACI]) have MACI, as intraarticular injections, or as an adjuvant to proven to lead to superior morphological, biological, and other treatments.3,7,8 clinical cartilage repair outcomes compared with alternative 1,2 treatments. The ACI procedure, however, has a number of 1Orthopedic Research Laboratory, Aarhus University Hospital, Aarhus drawbacks. It requires 2 separate surgeries, has a limited N, Denmark availability of donor cartilage, and requires an interposed 2Department of Radiology, Aarhus University Hospital, Aarhus N, and very costly laboratory chondrocyte culturing step.3 Denmark 3 Mesenchymal stem cells (MSCs) was originally pro- Department of Orthopedics, Aarhus University Hospital, Aarhus N, Denmark posed as a cell source for cartilage repair with a less inva- sive sample harvesting yielding highly proliferative cells Corresponding Author: able to undergo chondrogenic differentiation in vitro and Kris Tvilum Chadwick Hede, Orthopaedic Research Lab, Aarhus 4-6 University Hospital, Palle Juul-Jensens Boulevard 99, Section J, Level 1, produce hyaline-like cartilage. However, use of cultured Aarhus 8200, Denmark. MSCs has the same high costs as ACI. Therefore, there is Email: [email protected] 2 CARTILAGE 00(0) Currently, bone marrow cells are utilized clinically as a Patients cell source in marrow-stimulating cartilage repair tech- niques such as microfracture and subchondral drilling. In Patients suffering from large full-thickness cartilage these techniques the available MSCs for the cartilage repair lesions on patella or the femoral condyles were included in the study. Inclusion criteria were the following: symptom- is much smaller compared with MSCs in bone marrow 2 8 atic focal chondral lesions between 2 and 8 cm grade 3 or aspirated from the iliac crest. MSCs represent only 0.001% 9-12 4 using the ICRS (International Cartilage Repair Society) to 0.02% of the nucleated cells in bone marrow. In spite classification based on MRI or previous arthroscopy, age of their small proportion, the MSCs may promote healing between 18 and 50 years, ASA (American Society of through a paracrine effect on the surrounding tissue.13 In Anesthesiologists) group 0 to 2, and patient agreement to vivo studies applying the premise of MSCs as donor cells follow rehabilitation protocol and to attend follow-up for differentiation into chondrocytes have been with vary- visits. ing outcomes.5,14-17 More recently, the role of MSCs as Exclusion criteria were diagnosed malignancy, tricom- differentiating cells has been questioned, and several partmental arthritis, injury diagnosed as osteochondritis studies highlight their potential pivotal role in the regen- dissecans, untreated meniscal lesion, untreated ruptures of erative microenvironment in vivo as medicinal drugstores the cruciate and collateral ligaments, knee axis malalign- for immunomodulation and anabolic stimulation of host ment 5° based on clinical evaluation, rheumatoid arthritis, cells.6,18-24 Furthermore, BMAC is a rich source of growth > Mb. Bechterew, poor general health ASA 3 or higher, alco- factors that promote chondrogenesis.25,26 hol or drug abuse, and systemic or intraarticular corticoid Platelet-rich plasma (PRP) is an increasingly popular steroid treatment within the past 6 months. source of autologous growth factors and bioactive pro- Eight patients had the cartilage lesion(s) in the patella, 2 teins released on platelet activation, which are believed to patients in the trochlea, and 1 patient in the medial femoral promote cartilage matrix synthesis.27 Similar to BMAC, condyle. Patient demographics and characteristics are PRP can be administered as monotherapy as intraarticu- shown in Table 1. lar injections28 or as adjuvant to other cartilage repair treatments.29 A strategy using BMAC seeded onto a collagen I/III Preparation of BMAC, PRP, and Thrombin scaffold (Chondro-Gide) with or without PRP has been pro- BMAC, PRP, and thrombin were prepared according to posed and has shown promising clinical results with regards manufacturer’s instructions (Zimmer Biomet, Winterthur, to subjective clinical outcome and magnetic resonance 3,30,31 Switzerland). After the patient was anaesthetized, bone imaging (MRI) evaluations. Improvements with regard marrow was aspirated from the posterior iliac crest using to the same outcomes have also been seen using other meth- 7,32,33 sterile technique. A small incision was made, and an ods to deliver the BMAC. There are, however, only 11-gauge needle was used to enter the marrow cavity. few studies evaluating both the clinical and histological Twenty-four to 48 mL of bone marrow were aspirated into responses of BMAC for cartilage repair and further studies a heparin-coated (1000 U/mL) syringe containing 6 to 12 are needed to determine the indications, effects, and the best 34,35 mL ACD-A (Anti-coagulant Citrat Dextrose Solution A). applications of BMAC. The bone marrow aspirate was concentrated using a The aim of this study was to evaluate the clinical and MarrowStim Mini Concentration System (Zimmer Biomet). biological outcome of combined BMAC and PRP on a col- Centrifugation was performed for 15 minutes at 3200 rpm. lagen I/III scaffold for cartilage repair in the knee. We For PRP preparation, 27 mL of whole blood was aspi- hypothesized that the treatment would result in improve- rated into a heparin-coated (1000 U/mL) syringe contain- ment in subjective clinical outcome and result in hyaline ing 3 mL ACD-A and 3 mL PRP was yielded using a Mini and fibrocartilaginous repair tissue evaluated by MRI and GPS III Platelet Separation System (Zimmer Biomet). histologic evaluation of second-look biopsies. Centrifugation was performed for 15 minutes at 3200 rpm. For thrombin, 11 mL of whole blood was aspirated into a Materials and Methods heparin-coated (1000 U/mL) syringe containing 1 mL ACD-A (Zimmer Biomet). Thrombin was yielded using a The study was a prospective case series of 11 knees (10 Clotalyst Autologous Clotting Factor (Zimmer Biomet). patients) (mean age 29.4 years, range 18-36) with large full- thickness cartilage lesions that underwent surgical cartilage repair treatment at Aarhus University Hospital, using BMAC Surgery and PRP on a collagen I/III scaffold. The local ethics com- Prior to the open-surgery procedure, a knee arthroscopy mittee under the Danish National Committee on Health was performed to identify the defect and additional joint Research Ethics approved the protocol (#M-2014-389-14). pathology. Hede et al. 3 Table 1. Patient Demographics and Lesion Details (Intraoperatively Measured Defect Sizes). Patient/ Lesion Side