Fabrication of individual scaffolds based on a patient-specific alveolar bone defect model
Introduction
Dental implant restorations have become the standard method for reconstructing occlusions (Yamada et al., 2004). Sufficient bone volume in the implant area is a prerequisite for implant insertion, and is a critical factor for ensuring successful dental implantation (Ueda et al., 2001). However, alveolar bone defects stem from a variety of processes (such as disused absorption of alveolar bone after tooth loss, trauma, tumors, and periodontal diseases), resulting in insufficient bone volume in the implant area and the inability to implant. A number of approaches have attempted to repair alveolar bone defects in the implant area, including guided bone regeneration, distraction osteogenesis, and bone grafting techniques such as autologous iliac transplantation (Aghaloo and Moy, 2007). Recently, bone tissue engineering on porous three-dimensional (3D) scaffolds (Scheller et al., 2009) has shown great promise as a potential technique for alveolar bone defect repair.
Tissue engineering is dedicated to the development of biosubstitutes for restoring, maintaining, or improving the morphology and functions of damaged tissues or organs (Langer and Vacanti, 1993). While tissue engineering has been employed to repair damaged organs such as livers, hearts, and bones, bone tissue engineering may be one of the first techniques to enjoy successful clinical application (Service, 2000). Controlled 3D biodegradable scaffolds that serve as templates for initial cell attachment and subsequent tissue regeneration are critical for the success of bone tissue engineering (Vozzi et al., 2003). Since there are individual variations among patients and differences in damaged parts, bone tissue engineering scaffolds need to be custom-made to meet individual patient needs. Fabricating scaffolds precisely according to the 3D shape of the patient's bone defects will also improve the biocompatibility of scaffolds following implantation (Uchida et al., 2008). Although various attempts have been made to fabricate scaffolds according to the shape of patient bone defects (Dyson et al., 2007, Hollister et al., 2000, Sanz-Herrera and Garcia-Aznar, 2009, Wang et al., 2009, Wettergreen et al., 2005), scaffolds have not been formulated that truly reproduce patient-specific bone defects.
Traditional methods for the fabrication of bone tissue engineering scaffolds include particulate leaching, electro-spinning, multilayer lamination, and molding (Borden et al., 2002). Since these methods are limited by manual intervention, discordant fabrication processes, weak ductility, and the use of pore-forming agents (Leong et al., 2003), microscopic and macroscopic 3D scaffold shapes are unable to meet patient-specific clinical application needs. Recent advances in computer science and its integration with biomaterials and engineering have led to the emergence of new rapid prototyping technologies for producing 3D constructs, including stereolithography (Chu et al., 2002), fused deposition modeling (Chen et al., 2005, Hutmacher et al., 2001, Kalita et al., 2003, Zein et al., 2002), 3D printing (Chumnanklang et al., 2007, Lam et al., 2002, Tay et al., 2007), and selective laser sintering (Goodridge et al., 2007, Leong et al., 2003, Tan et al., 2003). These technologies produce controlled porous architectures less than 200 μm in size, but are limited at the 200–500 μm scale necessary for vascularization and bone tissue regeneration. Recently, our laboratory established a unique method based on the layer-by-layer manufacturing principle of solid freeform fabrication for 3D bone tissue engineering scaffolds (Xiong et al., 2001, Xiong et al., 2002, Yan et al., 2005). This method generates custom-made bone tissue engineering scaffolds according to the 3D shapes of patient bone defects, and easily produces controlled porous architectures in the range of 200–500 μm.
The aim of this study was to fabricate patient-specific alveolar bone tissue engineering composite scaffolds made of poly(lactide-co-glycolide) (PLGA) and tricalcium phosphate (TCP). A 3D model of the patient's alveolar bone defect was obtained from a computed tomography (CT) scan of the mandibular bone of a volunteer who lost the left mandible premolar and experienced heavy absorption of alveolar bone. Computer-aided low-temperature deposition manufacturing (LDM) was used to successfully tailor the PLGA/TCP composite scaffolds. The resulting PLGA/TCP scaffolds were characterized by scanning electron microscopy (SEM), liquid displacement, and mechanical bend testing, and biocompatibility was confirmed by attachment and proliferation of human bone marrow mesenchymal stem cells (HBMSCs).
Section snippets
Bone defect 3D model reconstruction
The process of reconstructing the 3D model of the patient's alveolar bone defect is illustrated in Fig. 1. The CT data were obtained with informed consent from a patient (38 years old, female) who wanted a dental implant to correct her loss teeth #34 and #35; alveolar bone in the tooth-loss area was absorbed heavily, and her other teeth and periodontal tissues were healthy. The patient was processed through the Beijing Stomatological Hospital affiliated with Capital Medical University, Beijing,
Results
The 3D model of the patient's alveolar bone defect was saddle-shaped (Fig. 3a–c). From the CT data used to construct the model, an individual scaffold made of PLGA/TCP was successfully fabricated. The resulting PLGA/TCP alveolar bone tissue engineering scaffold fabricated with the LDM technology was also saddle-shaped, identical to the patient-specific alveolar bone defect (Fig. 3d and e). The scaffolds were studded with quasi-circular and oval large pore structures on the radial surface and
Discussion
This study has demonstrated that individualized tissue engineering scaffolds based on patient-specific alveolar bone defects can be successfully fabricated by applying LDM. The resulting 3D shape of the individualized scaffold is almost identical to the model of the alveolar bone defects (Fig. 3a–c). This development not only satisfies the requirement that clinically relevant bone tissue engineering scaffolds be custom-made according to the 3D shape of the bone defects, but also improves the
Conclusion
Customized porous PLGA/TCP scaffolds were fabricated using a computer-aided LDM method. This technique allowed the successful development of a patient-specific scaffold based on a model of an alveolar bone defect obtained from CT images. The PLGA/TCP scaffolds formed by the LDM system have porosity up to 87.4% and porous morphologies suitable for vascularization and bone tissue regeneration. The mechanical properties of the scaffolds are similar to cancellous bones and much lower than cortical
Acknowledgment
The authors wish to thank members of the Key Laboratory for Advanced Materials Processing Technology, Tsinghua University, Beijing, China, for their assistance in the fabrication of PLGA/TCP scaffolds.
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