Tissue engineering rib with the incorporation of biodegradable polymer cage and BMSCs/decalcified bone: an experimental study in a canine model

Journal of Cardiothoracic Surgery, May 2013

Background The reconstruction of large bone defects, including rib defects, remains a challenge for surgeons. In this study, we used biodegradable polydioxanone (PDO) cages to tissue engineer ribs for the reconstruction of 4cm-long costal defects. Methods PDO sutures were used to weave 6cm long and 1cm diameter cages. Demineralized bone matrix (DBM) which is a xenograft was molded into cuboids and seeded with second passage bone marrow mesenchymal stem cells (BMSCs) that had been osteogenically induced. Two DBM cuboids seeded with BMSCs were put into the PDO cage and used to reconstruct the costal defects. Radiographic examination including 3D reconstruction, histologic examination and mechanical test was performed after 24 postoperative weeks. Results All the experimental subjects survived. In all groups, the PDO cage had completely degraded after 24 weeks and been replaced by fibrous tissue. Better shape and radian were achieved in PDO cages filled with DBM and BMSCs than in the other two groups (cages alone, or cages filled with acellular DBM cuboids). When the repaired ribs were subjected to an outer force, the ribs in the PDO cage/DBMs/BMSCs group kept their original shape while ribs in the other two groups deformed. In the PDO cage/DBMs/BMSCs groups, we also observed bony union at all the construct interfaces while there was no bony union observed in the other two groups. This result was also confirmed by radiographic and histologic examination. Conclusions This study demonstrates that biodegradable PDO cage in combination with two short BMSCs/DBM cuboids can repair large rib defects. The satisfactory repair rate suggests that this might be a feasible approach for large bone repair.

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Tissue engineering rib with the incorporation of biodegradable polymer cage and BMSCs/decalcified bone: an experimental study in a canine model

Journal of Cardiothoracic Surgery Tissue engineering rib with the incorporation of biodegradable polymer cage and BMSCs/ decalcified bone: an experimental study in a canine model Hua Tang 0 Bin Wu 0 Xiong Qin 0 Lu Zhang Jim Kretlow Zhifei Xu 0 0 Department of Thoracic and Cardiovascular Surgery, Shanghai Changzheng Hospital, The Second Military Medical University , No.415 Fengyang Road, Shanghai 200003 , China Background: The reconstruction of large bone defects, including rib defects, remains a challenge for surgeons. In this study, we used biodegradable polydioxanone (PDO) cages to tissue engineer ribs for the reconstruction of 4cm-long costal defects. Methods: PDO sutures were used to weave 6cm long and 1cm diameter cages. Demineralized bone matrix (DBM) which is a xenograft was molded into cuboids and seeded with second passage bone marrow mesenchymal stem cells (BMSCs) that had been osteogenically induced. Two DBM cuboids seeded with BMSCs were put into the PDO cage and used to reconstruct the costal defects. Radiographic examination including 3D reconstruction, histologic examination and mechanical test was performed after 24 postoperative weeks. Results: All the experimental subjects survived. In all groups, the PDO cage had completely degraded after 24 weeks and been replaced by fibrous tissue. Better shape and radian were achieved in PDO cages filled with DBM and BMSCs than in the other two groups (cages alone, or cages filled with acellular DBM cuboids). When the repaired ribs were subjected to an outer force, the ribs in the PDO cage/DBMs/BMSCs group kept their original shape while ribs in the other two groups deformed. In the PDO cage/DBMs/BMSCs groups, we also observed bony union at all the construct interfaces while there was no bony union observed in the other two groups. This result was also confirmed by radiographic and histologic examination. Conclusions: This study demonstrates that biodegradable PDO cage in combination with two short BMSCs/DBM cuboids can repair large rib defects. The satisfactory repair rate suggests that this might be a feasible approach for large bone repair. Tissue engineering; Rib reconstruction; PDO; Long defect of bone - Background Rib defects are seen in many medical situations such as post excision of chest wall tumours [1,2], infection, necrosis [3], trauma and when part of a rib is used as the donor material to reconstruct other bone defects [4,5]. In the past, little attention was paid to rib defect reconstruction as it was always thought that to have little impact on respiratory function. With the development of improved surgical techniques and the increase of patient aesthetic concerns, rib reconstruction has gradually gained more attention. As rib defects are always large, to now there are few experimental reports on rib reconstruction. Tissue engineering has been demonstrated to be a viable technique for regenerating large segments of bone [6,7]; however, few attempts have been made to tissue engineer ribs where a complete segmental defect exists. When tissue engineering bone, two important factors must be considered chiefly among many othersseed cell and scaffold. Bone marrow mesenchymal stem cells (BMSCs) have repeatedly been demonstrated to be a suitable seed cell for bone tissue engineering [8-10]. As for the scaffold, significant research has been performed to identify the best material for bone tissue engineering. Autogenous bone is often considered to be the best scaffold for bone tissue engineering [8,11,12], but concerns over the limited ability and donor site morbidity limit its use in the treatment of large defects, so allograft and xenograft bone often become the first choice in clinical applications. Polydioxanone (PDO), a synthetic resorbable polymer is now widely used as a suture material due to its strength and rate of degradation, but there are few reports about its use for other applications. Our previous work has included successful reconstruction of a chest wall defect spanning multiple ribs using a single PDO mesh [13]. For this study, we hypothesized that two 2-cm long DBM cuboids seeded with autogenous BMSCs could be placed with a 6-cm long PDO cage woven from PDO sutures and used to repair a 4-cm long single rib defect in the canine, proving the potential of reconstructing a single rib defect using multiple scaffolds seeded with BMSCs. We hypothesized that the PDO cage alone, or a PDO cage filled with two acellular cuboids would not equal the regenerative capability of the cell-seeded scaffolds. Methods Animals Twelve mongrel dogs aged 1 to 2 years, weighing 12 to 15 kg, were used in this study. The 4th and 7th ribs of each dog were made defect. All the 7th ribs were received PDO cage/DBMS/BMSCs, and six of all the 4th ribs received PDO cages/DBM or PDO cages (Table 1). The experimental protocol was approved by the Animal Care and Experiment Committee of The Second Military Medical University. Preparation of DBMs/BMSC (...truncated)


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Hua Tang, Bin Wu, Xiong Qin, Lu Zhang, Jim Kretlow, Zhifei Xu. Tissue engineering rib with the incorporation of biodegradable polymer cage and BMSCs/decalcified bone: an experimental study in a canine model, Journal of Cardiothoracic Surgery, 2013, pp. 133, 8, DOI: 10.1186/1749-8090-8-133