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Objective Single-surgery variants of autologous chondrocyte implantation to repair cartilage are emerging, but practical data on such procedures are scarce. We set out to describe a 1-stage autologous chondrocyte co-implantation procedure and include quantitative characteristics of the biopsy tissues collected and of the cells obtained from those tissues in the operating room. Design Data concerning patient age, articular cartilage lesion size and location, as well as measurements of cartilage biopsy mass, bone marrow aspirate volume, and the cell yields harvested from those biopsies were intraoperatively collected for 141 patients. Results The mean patient age was 35.7 ± 9.8 years, and the mean total lesion size was 4.0 ± 3.1 cm2. Cartilage biopsy mass ranged from 0.19 to 2.0 gram and provided a mean yield of 1.23 × 106 chondrocytes/gram. Bone marrow aspirate volume ranged from 7.2 to 62 milliliters and provided a mean yield of 7.18 × 106 mononuclear cells/mL. The cell yields did not correlate with patient age, which ranged from 12 to 57 years. The mean primary chondrocyte supply was 272 thousand per cm2 of lesion, ranging from 10.4 thousand to 1.07 million per cm2. The total cell supply was kept at 9 million cells per cm2 of lesion by adding mononuclear cells to the chondrocytes. The mean tissue processing time was 100 ± 19 minutes, which was frequently used to perform concurrent interventions. Conclusion Single-surgery co-implantation of clinically relevant numbers of autologous primary articular chondrocytes and bone marrow cells is feasible for a wide range of ages and lesion sizes.

Background: There is an unmet need for a single-stage cartilage repair treatment that is cost-effective and chondrocyte-based. Purpose: To evaluate the safety and preliminary efficacy of autologous freshly isolated primary chondrocytes and bone marrow mononucleated cells (MNCs) seeded into a PolyActive scaffold in patients with symptomatic cartilage lesions of the knee. Study Design: Case series; Level of evidence, 4. Methods: A total of 40 patients with symptomatic knee cartilage lesions were treated with freshly isolated autologous chondrocytes combined with bone marrow MNCs delivered in a biodegradable load-bearing scaffold. The treatment requires only 1 surgical intervention and is potentially a cost-effective alternative to autologous chondrocyte implantation. The primary chondrocytes and bone marrow MNCs were isolated, washed, counted, mixed, and seeded into a load-bearing scaffold in the operating room. Patients were followed up at 3, 6, 12, 18, and 24 months. Primary endpoints were treatment-related adverse events up to 3 months, adverse implant effects between 3 and 24 months, and the implant success rate at 3 months as measured by lesion filling. Results: Successful lesion filling (≥67% on magnetic resonance imaging) was found in 40 patients at 3 months and in 32 of the 32 patients analyzed at 24 months. Significant improvement over baseline was found for visual analog scale for pain from 3 months onward; Knee injury and Osteoarthritis Outcome Score (KOOS)-Pain and KOOS-Activities of Daily Living from 6 months onward; for KOOS-Symptoms and Stiffness, KOOS-Quality of Life and International Knee Documentation Committee from 12 months onward; and for KOOS-Sport and Recreation from 18 months onward. Hyaline-like repair tissue was found in 22 of 31 patients available for biopsy. Arthralgia and joint effusion were the most common adverse events. Scaffold delamination and adhesions led to removal of the implant in 2 patients. Conclusion: The treatment of knee cartilage lesions with autologous primary chondrocytes and bone marrow MNCs, both isolated and seeded into a load-bearing PolyActive scaffold within a single surgical intervention, is safe and clinically effective. Good lesion fill and sustained clinically important and statistically significant improvement in all patient-reported outcome scores were found throughout the 24-month study. Hyaline-like cartilage was observed on biopsy specimen in at least 22 of the 40 patients. Registration: NCT01041885 (ClinicalTrials.gov identifier)

Stem cells have for many years been gaining interest in the context of their potential applications in the tissue engineering-based treatment of musculoskeletal disorders. What made them such an attractive topic was that mesenchymal stem cells (MSCs) are capable of differentiating into one of several mesenchymal phenotypes such as osteoblasts, chondrocytes, myocytes, marrow stromal cells, tendon-ligament fibroblasts, and adipocytes. However, it seems that their most promising activity is a trophic effect on surrounding cells and tissues. MSCs secrete bioactive factors that suppress the local immune system; inhibit fibrosis, scar formation, and apoptosis; enhance angiogenesis; and stimulate mitosis and differentiation of tissue-intrinsic reparative or stem cells. MSCs respond to inflammation and fibrotic environment and control nociceptive pathways. Trophic and immunomodulatory behaviour of mesenchymal stem cells can be effectively used in tissue reconstruction based on cell transplantation. In these situations, MSCs possibly help other cells and protect against a hostile environment at the site of damage. In this approach, MSCs should be perceived in a different way than previously, which assumed that they are the building blocks of new tissue, or rather become a powerful tool in tissue regeneration, as cells supervising and supporting by organising the ideal environment for tissue regeneration.

Tissue engineering provides a promising alternative therapy to the complex surgical reconstruction of auricular cartilage by using ear-shaped autologous costal cartilage. Bacterial nanocellulose (BNC) is proposed as a promising scaffold material for auricular cartilage reconstruction, as it exhibits excellent biocompatibility and secures tissue integration. Thus, this study evaluates a novel bilayer BNC scaffold for auricular cartilage tissue engineering. Bilayer BNC scaffolds, composed of a dense nanocellulose layer joined with a macroporous composite layer of nanocellulose and alginate, were seeded with human nasoseptaLchondrocytes (NC) and cultured in vitro for up to 6 weeks. To scale up for clinical translation, bilayer BNC scaffolds were seeded with a low number of freshly isolated (uncultured) human NCs combined with freshly isolated human mononuclear cells (MNC) from bone marrow in alginate and subcutaneously implanted in nude mice for 8 weeks. 3D morphometric analysis showed that bilayer BNC scaffolds have a porosity of 75% and mean pore size of 50 +/- 25 pm. Furthermore, endotoxin analysis and in vitro cytotoxicity testing revealed that the produced bilayer BNC scaffolds were non-pyrogenic (0.15 +/- 0.09 EU/ml) and non-cytotoxic (cell viability: 97.8 +/- 4.7%). This study demonstrates that bilayer BNC scaffolds offer a good mechanical stability and maintain a structural integrity while providing a porous architecture that supports cell ingrowth. Moreover, bilayer BNC scaffolds provide a suitable environment for culture-expanded NCs as well as a combination of freshly isolated NCs and MNCs to form cartilage in vitro and in vivo as demonstrated by immunohistochemistry, biochemical and biomechanical analyses. (C) 2014 Elsevier Ltd. All rights reserved.