Tissue Eng Part A. 2014 Sep;20(17-18):2291-304.

Osteochondral repair using a scaffold-free tissue-engineered construct derived from synovial mesenchymal stem cells and a hydroxyapatite-based artificial bone.

Shimomura K, Moriguchi Y, Ando W, Nansai R, Fujie H, Hart DA, Gobbi A, Kita K, Horibe S, Shino K, Yoshikawa H, Nakamura N.

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan



For an ideal osteochondral repair, it is important to facilitate zonal restoration of the subchondral bone and the cartilage, layer by layer. Specifically, restoration of the osteochondral junction and secure integration with adjacent cartilage could be considered key factors. The purpose of the present study was to investigate the feasibility of a combined material comprising a scaffold-free tissue-engineered construct (TEC) derived from synovial mesenchymal stem cells (MSCs) and a hydroxyapatite (HA) artificial bone using a rabbit osteochondral defect model. Osteochondral defects were created on the femoral groove of skeletally mature rabbits. The TEC and HA artificial bone were hybridized to develop a combined implant just before use, which was then implanted into defects (N= 23). In the control group, HA alone was implanted (N= 18). Histological evaluation and micro-indentation testing was performed for the evaluation of repair tissue. Normal knees were used as an additional control group for biomechanical testing (N= 5). At hybridization, the TEC rapidly attached onto the surface of HA artificial bone block, which was implantable to osteochondral defects. Osteochondral defects treated with the combined implants exhibited more rapid subchondral bone repair coupled with the development of cartilaginous tissue with good tissue integration to the adjacent host cartilage when assessed at 6 months post implantation. Conversely, the control group exhibited delayed subchondral bone repair. In addition, the repair cartilaginous tissue in this group had poor integration to adjacent cartilage and contained clustered chondrocytes, suggesting an early osteoarthritis (OA)-like degenerative change at 6 months post implantation. Biomechanically, the osteochondral repair tissue treated with the combined implants at 6 months restored tissue stiffness, similar to normal osteochondral tissue. The combined implants significantly accelerated and improved osteochondral repair. Specifically, earlier restoration of subchondral bone, as well as good tissue integration of repair cartilage to adjacent host tissue could be clinically relevant in terms of the acceleration of postoperative rehabilitation and longer-term durability of repaired articular surface in patients with osteochondral lesions, including those with OA. In addition, the combined implant could be considered a promising MSC-based bio-implant with regard to safety and cost-effectiveness, considering that the TEC is a scaffold-free implant and HA artificial bone has been widely used in clinical practice.

PMID: 24655056



Many therapeutic procedures have been investigated to biologically repair damaged cartilage, and successful results have been obtained in some clinical studies. On the other hand, the incidence of OA, which involves subchondral bone pathology, is higher than that of isolated chondral injury. Therefore, the development of novel therapeutic methods for osteochondral repair is urgent, considering the large number of OA patients. Recently, tissue engineering approaches using biphasic or triphasic implants have been tested and proved to be efficient in osteochondral damage. These constructs should be reasonable for osteochondral repair due to both mechanical and biological reasons such as acquisition of initial mechanical strength, mimicking a natural articular structure, a uniform tidemark at the osteochondral junction, and integration of the implant with host tissue to sustain biological function. This is the first study to focus on the detailed process of osteochondral repair using biphasic implant with time course transitions. Through the comparison of biphasic implant with artificial bone alone, we have demonstrated the significance of the combination of stem cell-based TEC with artificial bone in the process of osteochondral repair.

A scaffold-free three-dimensional TEC is composed of MSCs and extracellular matrices synthesized by the cells. These TEC are developed without any artificial scaffold, and, thus, their implantation could eliminate the risk of potential side effects induced by extrinsic chemical or biological materials. Furthermore, such TEC are highly adherent to cartilage matrix, and secure integration to adjacent cartilage tissue is observed after implantation. Similarly, the hybridization of the TEC with the HA artificial bone can be simply accomplished, as it occurs immediately after the contact of these two materials without any reinforcement for fixation, unlike previously reported biphasic materials, which needed some adhesive or glue to combine different materials and required a complicated process of manufacturing implants. This stable association led to the development of secure tissue integration between the repair cartilage and subchondral bone. The tight association between the TEC and the HA artificial bone may be based on the high affinity of HA for glycoproteins that are enriched in these TEC, and such a simple and efficient procedure has made it possible to associate these two materials just before use in the surgical model. Taken together, the TEC-HA combined implant could be advantageous not only with regard to safety, but also related to time- and cost effectiveness.


Figure 1 jep

Figure: Schematic representation of osteochondral repair with the combined implant of TEC and HA artificial bone



Norimasa Nakamura, MD, PhD

Institution: Institute for Medical Science in Sports, Osaka Health Science University

Address: 1-9-27, Tenma, Kita-ku, Osaka City, Osaka, 530-0043, Japan

Tel: +81 6 6352 0093 Fax: +81 6 6352 5995

E-mail: norimasa.nakamura@ohsu.ac.jp


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