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 In all groups, the PDO cage had completely degraded after 24 weeks and been replaced by fibrous tissue.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
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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)