|Year : 2018 | Volume
| Issue : 4 | Page : 79-82
The efficacy of double-tube polycaprolactone/β-tricalcium phosphate bioceramic composite in the treatment of bone defects
Genwei Guo, Gentao Fan, Xiaozhou Liu, Xin Shi, Guangxin Zhou, Xing Zhou
Department of Orthopaedics, Eastern Theater General Hospital, Nanjing, Jiangsu, China
|Date of Submission||28-Nov-2018|
|Date of Acceptance||18-Dec-2018|
|Date of Web Publication||26-Dec-2018|
Dr. Xing Zhou
Department of Orthopaedics, Eastern Theater General Hospital, Nanjing 210002, Jiangsu
Source of Support: None, Conflict of Interest: None
Aim: The study aims to investigate the efficacy of double-tube polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) bioceramic composites in the treatment of bone defects. Methods: Forty healthy female New Zealand white rabbits, aged 6–10 months and weighing about 3 kg, were randomly divided into observation group (n = 20) and control group (n = 20) according to the random number table. The animals in the observation group were implanted with double-tube PCL/β-TCP bioceramic composites, and the control animals were implanted with single-tube porous β-TCP bioceramic scaffolds. At 12 weeks' postoperatively, the osteogenic effects between two groups were compared by local X-ray film, local bone appearance, histology, osteogenic area per field, and compression strength measured after sacrifice. Results: At 12 weeks after surgery, X-ray, bone appearance, histological staining, and osteogenic area per field showed that the scores in the observation group were significantly better than the control group (P < 0.05). Furthermore, the compression strength of the regenerated bone in the observation group was significantly higher than that of the control group (P < 0.05). Conclusion: The double-tube PCL/β-TCP bioceramic composite has promising therapeutic effects, osteogenic effect and mechanical properties in the treatment of bone defects, and thus may be of clinical significance.
Keywords: Bone defect, double-tube polycaprolactone/β-tricalcium phosphate bioceramic composite, osteogenic effect
|How to cite this article:|
Guo G, Fan G, Liu X, Shi X, Zhou G, Zhou X. The efficacy of double-tube polycaprolactone/β-tricalcium phosphate bioceramic composite in the treatment of bone defects. Transl Surg 2018;3:79-82
|How to cite this URL:|
Guo G, Fan G, Liu X, Shi X, Zhou G, Zhou X. The efficacy of double-tube polycaprolactone/β-tricalcium phosphate bioceramic composite in the treatment of bone defects. Transl Surg [serial online] 2018 [cited 2020 Feb 29];3:79-82. Available from: http://www.translsurg.com/text.asp?2018/3/4/79/248613
| Introduction|| |
The bone defect is a common condition. Severe trauma, inflammation, tumor, and others are the common causes of bone defects. Clinical treatment is challenging due to long-term treatment course and high cost. At present, surgery is the mainstay treatment for bone defects, and the selection of suitable implants to replace tissue defects to reestablish structural integrity is the key in surgical treatment. The irregularity of the tissue defect frequently causes the mismatch between the implant and the defect area, and repeated shaping and matching of the conventional implant during the operation are required. This not only is challenging for the medical team but also causes unexpected postoperative adverse osteogenic effect and unanticipated intensity, which affects the efficacy of surgical treatment. Therefore, it is necessary to find an effective implant to quickly and effectively complete the repair process of the defect.,,, In this study, we focused on the efficacy of dual-tube polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) bioceramic composites in the treatment of bone defects and aimed to provide reference values for clinical treatment.
| Methods|| |
Experimental animals, materials, and instruments
Animals and instruments
Forty healthy female New Zealand white rabbits, aged 6–10 months and weighing about 3 kg, were provided by the Experimental Animal Center of Nanjing Medical University. All the procedures on the animals were approved by the Ethics Committee.
Following instruments were used in this study: penicillin sodium, inverted phase contrast microscope, cell culture incubator, sterile surgical package, medical wire saw, conventional surgical instruments, and medical X-ray machine.
Structure design of scaffold
The establishment of double-tube composite model: The space between adjacent tubes at each level was set as 1200 μm, the tube diameter was 300 μm, and the external dimension was 4.8 mm × 4.5 mm × 4.5 mm; the involved primary and secondary tubes were not connected to each other. Primary tubes were mainly used for nutrient metabolism, cell attachment, and tissue penetration, while PCL-perfused secondary tubes were mainly used to enhance scaffold strength. Meanwhile, a single-tube porous β-TCP bioceramic scaffold with only primary tube was designed as a control group, which had the same macroporosity as the double-tube composite scaffold.
Preparation of the scaffold
First, the reverse model of the scaffold was obtained by Boolean operation according to the double-tube composite scaffold model, and then, the data of reverse model were introduced into the photocuring rapid prototyping machine to manufacture a resin mold. Then, the β-TCP bioceramic slurry was prepared, and the prepared material was poured into the resin mold. After solidification, the procedures of drying, stripping, and sintering (sintered in a high-temperature resistance furnace) were completed to obtain a double-tube β-TCP bioceramic scaffold. The secondary tubes in double-tube β-TCP bioceramic scaffold were filled with PCL to construct a double-tube composite scaffold. To ensure that the molten PCL does not enter the primary tube of the scaffold, but only perfuse into its secondary tube, most of the primary tubes were temporarily hidden inside the scaffold when the β-TCP bioceramic scaffold was designed and prepared. After the PCL was poured into the secondary tubes of the scaffold and cooled, the primary tubes of the scaffold were then exposed, and a double-tube composite scaffold was constructed. The preparation method of the single-tube scaffold was consistent with the double-tube composite scaffold. First, a reverse model of single-tube scaffold was designed. The data of the reverse model were imported into a photo-curing rapid prototyping machine to prepare a resin mold. Then, the β-TCP bioceramic slurry was poured, freeze-dried under vacuum, demolded and sintered to obtain a single-tube scaffold.
The rabbits were anesthetized with 50 mg/kg pentobarbital sodium through ear vein injection, and surgery area on the left hind limb was subject to local anesthesia with lidocaine. Routine skin preparation, disinfection, and toweling were completed subsequently. From the lateral side of the knee joint, the external femoral condyle of the rabbit, an approximation of the platform-like structure that could be touched, was located. The knees of the hind legs of the rabbits were slightly flexed, the skin was tightened to avoid the subcutaneous blood vessels, and the skin, subcutaneous tissue, and fascia were incised obliquely. The incision was about 2.0 cm long, exposing the lateral epicondyle of the femur, and the tendon attached thereto was peeled off. There was an obvious metaphyseal line at the transition of the femoral shaft and the femoral condyle. A circular drill with 7 mm diameter was used to drill a vertical depth of about 8 mm and the bone was carefully removed. There was only a thin layer of cortical bone at outer layer, the rest were cancellous bone structures, and the periosteum at the defect site was removed. The normal saline of 4°C was used for intraoperative cooling. The depth sounder was used to detect the defect depth, and the scoop was used for delicate trimming. The diameter of the bone defect was 7 mm, and the depth was 8 mm. The animals in the observation group were implanted with double-tube PCL/β-TCP bioceramic composite material, and the animals in the control group were implanted with single-tube porous β-TCP bioceramic scaffold.
X-ray images of the femur were performed at 12 weeks' postsurgery (projection distance was 1 m, projection settings were 46 kV, 50 mA, and exposure time was 0.14 s), and the bioscaffold material degradation and bone defect repairing were observed, which were classified as excellent, good, fair, or poor, each term defined as: (1) excellent – The bone defect area and the bone stump start to bridge and heal, the boundary is unclear, the callus starts to shape; (2) good – The bone defect area presents as a large sheet-like projection resistance shadow, the scaffold material is degraded and absorbed, and the callus is obvious; (3) fair – The bone defect area presents as a smaller flake-like or larger dot-shaped projection resistance shadow, the scaffold material is partially degraded and absorbed, and the callus is not obvious; and (4) poor – the bone defect area presents as spotted projection resistance shadow, and the scaffold material is clearly visible. At 12 weeks' postsurgery, the animals were sacrificed by air embolization and assessed for (1) the anatomy of the injured area; (2) appearance of local bone: The growth of new bone in the defect area was observed; (3) histology: The femur was taken out, routinely decalcified, embedded with paraffin, serially sliced into slices of 5 μm thickness, hematoxylin, and eosin staining was performed to observe the repaired structure of bone defect area under light microscope; (4) osteogenic area per unit field: the photographs of slices were taken by the digital camera, and osteogenic area per unit field was measured by the Beihang automatic image analysis system; and (5) compressive strength: The material at 3 cm from the distal end of the femur was collected to detect the compressive strength of the bone, and the mechanical properties of two groups were compared.
Data were analyzed using SPSS 22.0 software (IBM, New York, USA). The data which satisfied normal distribution were presented as Mean ± standard deviation. The enumeration data were presented as case number or percentage, and the percentage was compared with the Chi-square test; the comparisons among groups and comparisons within groups were completed with t-test. P < 0.05 was considered statistically significant.
| Results|| |
Comparison of X-ray evaluation between two groups
The percentage of number of cases classified as excellent and good healing was higher in the observation group (92.00%) than in that of the control group (60.00%); (P < 0.05), as shown in [Table 1].
Comparison of bone appearance between two groups
Materials in both groups were partially absorbed, and the bone defect area was significantly smaller than before. New bone hyperplasia and filling were found, bone filling was observed in the primary tube of the scaffold, which was more in the observation group than the control group.
Comparison of histological observations between two groups
The scaffold material was partially degraded and absorbed, and the new osteoid tissue was obviously increased, growing along the scaffold material. Osteoblasts were arranged along the scaffold and filled the primary tube, and the chondrocyte mass was observed. Newly regenerated bone in the observation group was more obvious than the control group.
Comparison of the osteogenic area per unit field between two groups
The osteogenic area per unit field in the observation group was larger than that of the control group, which was statistically significant (P < 0.05) [Table 2].
|Table 2: Comparison of the osteogenic area per unit field between two groups (x̄±s)|
Click here to view
Comparison of compressive strength between two groups
The maximum compressive strength of the observation group was higher than that of the control group, which was statistically significant (P < 0.05) [Table 3].
| Discussion|| |
In the field of orthopedics, bone defects due to various causes such as severe trauma and bone tumors are common, and the incidence rate is increasing which seriously affects people's physical and mental health and quality of life., What kind of materials should be used and how to implement bone grafting has always been an important topic worthy of research. At present, bone repair materials frequently used in clinical practice mainly include metal prostheses and autologous bones. The metal prosthesis has disadvantages of poor histocompatibility, fracture, loosening, and nondegradability; although autologous bone is a clinically ideal bone defect repair material, it will increase the pain and trauma in patients, and cannot meet the needs for large segmental bone graft procedures.,,, Therefore, the development of ideal artificial bone substitute in the field of medicine and biomaterials has become a research hotspot.
Bone tissue engineering provides a novel platform for repairing the bone defect. Porous scaffold is one of the important factors in the construction of tissue-engineered bone. It can be used as a medium for the interaction between extracellular matrix and cells, and can provide structural support for new tissue formation. β-TCP is a low-temperature phase of TCP, which has a low sintering temperature and can be prepared into a three-dimensional perforated widely connected microporous structure, similar to cancellous bone. The macroporous structure can provide space for extracellular matrix secretion, cell adhesion, and proliferation, thereby facilitating the growth of blood vessels and bone tissues; and the microporous structure can facilitate the penetration of tissue fluid. In addition, β-TCP scaffolds also have been demonstrated to have obvious advantages in bone formation and degradation rate and formation effect. Bone is a key organ for maintaining biological morphology; however, the mechanical strength of bioceramic scaffolds is relatively poor, thus limiting its clinical applications., Adding an organic polymer, capable of adjusting to physical and mechanical properties, and preparing a composite material scaffold is an effective approach to improve the strength of the bioceramic scaffolds. Several studies have reported that immersing the porous bioceramic scaffold in molten PCL to infiltrate into the space of the scaffold can establish a composite scaffold with higher mechanical strength. However, because the macroscopic space of the scaffold is full of PCL, it is difficult for the regenerated tissue to grow into the scaffold after implantation into the body. Therefore, to solve this problem, in our study, we used the double-tube PCL/β-TCP bioceramic composite material scaffold, in a way that there are primary and secondary tubes inside the scaffold, which are not connected and interlaced. The results showed that the maximum compressive strength of the regenerated bone in the observation group was higher than that of the control group, suggesting that the double-tube PCL/β-TCP bioceramic composite can enhance mechanical properties. Appearance and histology of the observation group at 12 weeks' postsurgery was superior to the control group. In X-ray evaluation, more animals were rated under excellent and good groups in observation group than control group. The osteogenic area per unit field was larger in observation group than those of the control group, suggesting a better osteogenic effect of the double-tube PCL/β-TCP bioceramic composite.
The double-tube PCL/β-TCP bioceramic composite has promising therapeutic effects, osteogenic effect and mechanical properties in the treatment of bone defects, and thus may be of clinical significance.
Financial support and sponsorship
This study was supported by Military Medical Scientific Research Foundation of China (15QNP023); National Natural Science Foundation of China (81802693).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Zheng C, Zhou YG, Ma HY, Zhang Z, Fu HH, Wu WM, Piao S, Du YQ, Wang S. Relationship between screw numbers and severity of tibial bone defect in primary total knee arthroplasty. Zhongguo Gu Shang
Deng Z, Huang D. Progress in the application of allogeneic bone grafting for bone defect repair. Shandong Med J
Pan W, Yuan M, Kou X, Yang H, Ma Y. Nursing care for hip revision patients with severe bone defect using 3D printing technology. Zhonghua Hu Li Za Zhi
Shi B. Application of 3D printing in repair of bone defect. Zhongguo Xian Dai Yi Sheng
Hwang KS, Choi JW, Kim JH, Chung HY, Jin S, Shim JH, Yun WS, Jeong CM, Huh JB. Comparative efficacies of collagen-based 3D printed PCL/PLGA/β-TCP composite block bone grafts and biphasic calcium phosphate bone substitute for bone regeneration. Materials (Basel)
2017;10 (4). pii: E421.
Wang Y, Pei G, Zhang H, Zhang Y, Wang G. An experimental model of bone defect at the rabbit femoral shaft to be used in bone tissue engineering research. Zhonghua Chuang Shang Gu Ke Za Zhi
Kang X, Zhao Z, Wu X, Shen Q, Wang Z, Kang Y, Xing Z, Zhang T. Experimental study on chitosan/allogeneic bone powder composite porous scaffold to repair bone defects in rats. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
Wang H, Gan Y, Li C, Cheng Q, Li L, Dong L, Cui X. Treatment of humeral bone defects with skin defects with bone-soft tissue composite transfer technique. Zhongguo Jiao Xing Wai Ke Za Zhi
Li H, Liu Y, Wang J, Gu S, Yin Q, Shen Y, Yang Y. Induced membrane technique for treatment of bone defects by extracorporeal formation of multi-column bone cement spacer. Zhongguo Xian Dai Yi Xue Za Zhi
Chen L, Chen Y, Wang Z, Wang Y, Zhang P. Preparation of collagen/hydroxyapatite composites and its research in the repair for bone defect. Zhonghua Sun Shang Yu Xiu Fu Za Zhi
Zhao W, Zhang Z, Yang B, Ye Y. Current status and research progress of heterogeneous bone graft and large bone defect repair. Xian Dai Lin Chuang Yi Xue
Wang X, Liu H. Research progress in repairing bone defect of implant site by autogenous bone grafting. Kou Qiang He Mian Xiu Fu Xue Za Zhi
Alike Y, Kasimu A, Abulaiti A, Yusufu A, Ayiti W. Application of three-dimensional printing customized bone cement models on repair of bone defect of limbs. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
Won JY, Park CY, Bae JH, Ahn G, Kim C, Lim DH, Cho DW, Yun WS, Shim JH, Huh JB. Evaluation of 3D printed PCL/PLGA/β-TCP versus collagen membranes for guided bone regeneration in a beagle implant mode. Biomed Mater
Park SH, Park SA, Kang YG, Shin JW, Park YS, Gu SR, Wu YR, Wei J. PCL/β-TCP composite scaffolds exhibit positive osteogenic differentiation with mechanical stimulation. J Tissue Eng Regen Med
Yeo MG, Kim GH. Preparation and characterization of 3D composite scaffolds based on rapid-prototyped PCL/β-TCP struts and electrospun PCL coated with collagen and HA for bone regeneration. Chem Mater
Jin GH, Kim GH. The effect of sinusoidal AC electric stimulation of 3D PCL/CNT and PCL/β-TCP based bio-composites on cellular activities for bone tissue regeneration. J Mater Chem B
[Table 1], [Table 2], [Table 3]