One-step surgery with multipotent stem cells and Hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45 years

PurposeThe aim of this study is to prospectively evaluate the medium-term effectiveness and regenerative capability of autologous adult mesenchymal stem cells, harvested as bone marrow aspirate concentrate (BMAC), along with a hyaluronan-based scaffold (Hyalofast) in the treatment of ICRS grade 4 chondral lesions of the knee joint, in patients older than 45 years.MethodsA study group of 20 patients with an age >45 years (mean 50.0 ± 4.1 years) was compared to a control group of 20 patients with an age <45 years (mean 36.6 ± 5.0). Patients were prospectively evaluated for 4 years. All patients were evaluated with MRI, KOOS, IKDC, VAS and Tegner scores preoperatively and at two-year and final follow-up.ResultsAt final follow-up, all scores significantly improved (P < 0.001) as follows: all KOOS score categories; Tegner 2 (range 0–4) to 6 (range 4–8) and 3 (range 0–6) to 6 (range 3–10); IKDC subjective (39.2 ± 16.5 to 82.2 ± 8.9) and (40.8 ± 13.9 to 79.4 ± 14.6), in the study and control group respectively. In addition, we show that results are affected by lesion size and number but not from concomitant surgical procedures. MRI showed complete filling in 80 % of patients in the study group and 71 % of patients in the control group. Histological analysis conducted in three patients from the study and two patients from the control group revealed good tissue repair with a variable amount of hyaline-like tissue.ConclusionTreatment of cartilage lesions with BMAC and Hyalofast is a viable and effective option that is mainly affected by lesion size and number and not by age. In particular, it allows to address the >45 years population with functional outcomes that are comparable to younger patients at final follow-up.Level of evidenceProspective cohort study, Level II.

[1]  B. Oakes,et al.  Autologous chondrocyte implantation for treatment of focal chondral defects of the knee--a clinical, arthroscopic, MRI and histologic evaluation at 2 years. , 2005, The Knee.

[2]  T. Trzaska,et al.  Articular cartilage defects: study of 25,124 knee arthroscopies. , 2007, The Knee.

[3]  Arnold I Caplan,et al.  The MSC: an injury drugstore. , 2011, Cell stem cell.

[4]  A. Gobbi,et al.  One-Step Cartilage Repair with Bone Marrow Aspirate Concentrated Cells and Collagen Matrix in Full-Thickness Knee Cartilage Lesions , 2011, Cartilage.

[5]  B. Beynnon,et al.  Knee Injury and Osteoarthritis Outcome Score (KOOS)--development of a self-administered outcome measure. , 1998, The Journal of orthopaedic and sports physical therapy.

[6]  Anup Kumar,et al.  Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes , 2014, Knee Surgery, Sports Traumatology, Arthroscopy.

[7]  Brunella Grigolo,et al.  Osteoarthritis treated with mesenchymal stem cells on hyaluronan-based scaffold in rabbit. , 2009, Tissue engineering. Part C, Methods.

[8]  B. P. Smith,et al.  Cartilage injuries: a review of 31,516 knee arthroscopies. , 1997, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[9]  Mitsuo Ochi,et al.  Articular cartilage repair using tissue engineering technique--novel approach with minimally invasive procedure. , 2004, Artificial organs.

[10]  I. Bellantuono,et al.  Study of Telomere Length Reveals Rapid Aging of Human Marrow Stromal Cells following In Vitro Expansion , 2004, Stem cells.

[11]  G. Lisignoli,et al.  Human chondrocytes and mesenchymal stem cells grown onto engineered scaffold. , 2006, Biorheology.

[12]  A. Thambyah,et al.  Treatment of Chondral Lesions in Advanced Osteochondritis Dissecans: A Comparative Study of the Efficacy of Chondrocytes, Mesenchymal Stem Cells, Periosteal Graft, and Mosaicplasty (Osteochondral Autograft) in Animal Models , 2004, Journal of pediatric orthopedics.

[13]  M. Saito,et al.  Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. , 2002, Osteoarthritis and cartilage.

[14]  A. Nixon,et al.  Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[15]  Ivan Martin,et al.  Age related changes in human articular chondrocyte yield, proliferation and post-expansion chondrogenic capacity. , 2004, Osteoarthritis and cartilage.

[16]  A. Gobbi,et al.  Rehabilitation After Knee Cartilage Transplantation with Autologous Chondrocytes or Stem Cells , 2014 .

[17]  A Stella,et al.  Mesenchymal stem cell interaction with a non‐woven hyaluronan‐based scaffold suitable for tissue repair , 2008, Journal of anatomy.

[18]  H. Mankin,et al.  The response of articular cartilage to mechanical injury. , 1982, The Journal of bone and joint surgery. American volume.

[19]  N. Nakamura,et al.  Next Generation Cartilage Solutions , 2012 .

[20]  I. Martin,et al.  Cartilage Repair in the Inflamed Joint: Considerations for Biological Augmentation Toward Tissue Regeneration. , 2016, Tissue engineering. Part B, Reviews.

[21]  N. Zini,et al.  Chondrogenic differentiation of bone marrow concentrate grown onto a hylauronan scaffold: rationale for its use in the treatment of cartilage lesions. , 2013, Journal of biomedical materials research. Part A.

[22]  A. Gobbi,et al.  One-Step Surgery With Multipotent Stem Cells for the Treatment of Large Full-Thickness Chondral Defects of the Knee , 2014, The American journal of sports medicine.

[23]  Stefano Zaffagnini,et al.  Arthroscopic Second-Generation Autologous Chondrocyte Implantation Compared with Microfracture for Chondral Lesions of the Knee , 2009, The American journal of sports medicine.

[24]  Kp Suresh,et al.  Sample size estimation and power analysis for clinical research studies , 2012, Journal of human reproductive sciences.

[25]  P. Benya,et al.  Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels , 1982, Cell.

[26]  Maurilio Marcacci,et al.  Patellofemoral Full-Thickness Chondral Defects Treated with Hyalograft-C , 2006, The American journal of sports medicine.

[27]  S. Giannini,et al.  Validity of T2 mapping in characterization of the regeneration tissue by bone marrow derived cell transplantation in osteochondral lesions of the ankle. , 2011, European journal of radiology.

[28]  H. Nejadnik,et al.  Autologous Bone Marrow–Derived Mesenchymal Stem Cells Versus Autologous Chondrocyte Implantation , 2010, The American journal of sports medicine.

[29]  F. Luyten,et al.  Donor site morbidity after articular cartilage repair procedures: a review. , 2010, Acta orthopaedica Belgica.

[30]  M. Brittberg,et al.  Treatment and Prevention of (Early) Osteoarthritis Using Articular Cartilage Repair—Fact or Fiction? A Systematic Review , 2013, Cartilage.

[31]  M. Goldring,et al.  Cartilage homeostasis in health and rheumatic diseases , 2009, Arthritis research & therapy.

[32]  J. Richmond,et al.  Development and Validation of the International Knee Documentation Committee Subjective Knee Form * , 2001, The American journal of sports medicine.

[33]  J. Lysholm,et al.  Rating systems in the evaluation of knee ligament injuries. , 1985, Clinical orthopaedics and related research.

[34]  P. Lenz,et al.  Autologous Chondrocyte Implantation for Treatment of Focal Cartilage Defects in Patients Age 40 Years and Older , 2010, The American journal of sports medicine.

[35]  N. Zini,et al.  Chondrogenic differentiation of murine and human mesenchymal stromal cells in a hyaluronic acid scaffold: differences in gene expression and cell morphology. , 2006, Journal of biomedical materials research. Part A.