Fabrication of a two-level tumor bone repair biomaterial based on a rapid prototyping technique

Key Laboratory for Advanced Materials Processing Technology, Ministry of Education & Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, People's Republic of China.
Biofabrication (Impact Factor: 4.29). 06/2009; 1(2):025003. DOI: 10.1088/1758-5082/1/2/025003
Source: PubMed


After the removal of the giant cell tumor (GCT) of bone, it is necessary to fill the defects with adequate biomaterials. A new functional bone repair material with both stimulating osteoblast growth and inhibiting osteoclast activity has been developed with phosphorylated chitosan (P-chitosan) and disodium (1 --> 4)-2-deoxy-2-sulfoamino-beta-D-glucopyranuronan (S-chitosan) as the additives of poly(lactic acid-co-glycolic acid) (PLGA)/calcium phosphate (TCP) scaffolds based on a double-nozzle low-temperature deposition manufacturing technique. A computer-assisted design model was used and the optimal fabrication parameters were determined through the manipulation of a pure PLGA/TCP system. The microscopic structures, water absorbability and mechanical properties of the samples with different P-chitosan and S-chitosan concentrations were characterized correspondingly. The results suggested that this unique composite porous scaffold material is a potential candidate for the repair of large bone defects after a surgical removal of GCT.

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    • "The composite scaffolds were fabricated using a lowtemperature biological-material rapid-prototyping device (3-D printer) (CLRF-2000-II, Tsinghua University, China) using an established protocol [33]. Briefly, PLGA was added with a powder weight to solution volume of 13:100 in organic solvent 1.4-dioxane. "
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    ABSTRACT: Bone graft substitutes are commonly used to treat large bone defects, particularly if they can additionally act as a local delivery system for therapeutic agents capable of enhancing bone regeneration. In this study, composite scaffolds made of poly (lactic-co-glycolic acid) (PLGA) and tricalcium phosphate (TCP) called P/T were fabricated by a low-temperature rapid prototyping technique. In order to optimise the delivery system, two different approaches for loading either the phytomolecule icaritin (ICT) or bone morphogenetic protein-2 (BMP-2) were developed for an in vivo efficacy study. One was an “incorporating approach” in which the growth factor was incorporated into the scaffold during fabrication, whereas the other was a “coating approach” in which the fabricated scaffold was immersed into a preparative solution containing the growth factor. Scaffolds incorporating these growth factors were termed P/T/ICT and P/T/BMP-2, while scaffolds that had these growth factors coated on to them were named, respectively, P/T + ICT and P/T + BMP-2. A P/T scaffold without any loading was used as the control. The bone regeneration effect of these scaffolds was compared in an ulnar bone defect model in rabbits. Bone regeneration and angiogenesis was evaluated by high-resolution peripheral quantitative computed tomography and magnetic resonance imaging postimplantation. Bone regeneration was better with the P/T/ICT scaffolds with an 83.8% improvement compared with the control, and a 72.0% improvement compared with the P/T/BMP-2 treatment. Although the P/T + BMP-2 scaffold demonstrated, as expected, the best overall bone regeneration, the P/T scaffold with incorporated ICT was shown to be an innovative and cost-effective bioactive scaffold which also significantly enhanced bone regeneration with the potential to be validated for orthopaedic applications.
    04/2014; 2(2):91–104. DOI:10.1016/
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    • "Three doses of ICT were prepared, with 0.013:100 as the P/T/LICT group, 0.052:100 as the P/T/MICT group and 0.13:100 as the P/T/HICT group, respectively, as reported in a recent in vitro study [6]. The organic reagent 1,4-dioxane was volatile and therefore could be entirely removed by a 24 h drying process in a freeze dryer with an ice condenser temperature of À55 °C and a negative pressure of 500 Pa [19] [21]. All scaffolds used in the animal model were trimmed down to 4 Â 4 Â 12 mm 3 to fit into the bone defects. "
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    ABSTRACT: Bone defect repair is challenging in orthopaedic clinics. For treatment of large bone defects, bone grafting remains the method of choice for the majority of surgeons as it fills spaces and provides support for enhancing biological bone repair. There has been around 2.2 million bone grafts used annually worldwide [1]. As therapeutic agents are desirable for enhancing bone healing, this study was designed to develop such a bioactive composite scaffold (PLGA/TCP/ICT) made of polylactide-co-glycolide (PLGA) and tricalcium phosphate (TCP) as a basic carrier incorporating a phytomolecule icaritin (ICT), i.e. a novel osteogenic exogenous growth factor. PLGA/TCP/ICT scaffolds were fabricated as PLGA/TCP (control group) and PLGA/TCP in tandem with low/mid/high dose ICT (LICT/MICT/HICT groups, respectively). To evaluate the in vivo osteogenic and angiogenic potentials of this bioactive scaffolds with slow release of osteogenic ICT, we established a 12 mm ulnar bone defect model in rabbits. X-ray and HR-pQCT results at weeks 2, 4 and 8 post-surgery showed more newly formed bone within bone defects implanted with PLGA/TCP/ICT scaffolds, especially PLGA/TCP/MICT scaffold. Histological results at weeks 4 and 8 also demonstrated more newly mineralized bone in PLGA/TCP/ICT groups, especially in PLGA/TCP/MICT group, correspondingly with more new vessels ingrowth. These findings may form a good foundation for potential clinical validation of this innovative bioactive scaffold incorporated with proper amount of osteopromotive phytomolecule ICT as a ready product for clinical applications.
    Acta biomaterialia 01/2013; 9(5). DOI:10.1016/j.actbio.2013.01.024 · 6.03 Impact Factor
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    ABSTRACT: This paper describes a multi-material virtual prototyping (MMVP) system for modelling and digital fabrication of discrete and functionally graded multi-material objects for biomedical applications. The MMVP system consists of a DMMVP module, an FGMVP module and a virtual reality (VR) simulation module. The DMMVP module is used to model discrete multi-material (DMM) objects, while the FGMVP module is for functionally graded multi-material (FGM) objects. The VR simulation module integrates these two modules to perform digital fabrication of multi-material objects, which can be subsequently visualized and analysed in a virtual environment to optimize MMLM processes for fabrication of product prototypes. Using the MMVP system, two biomedical objects, including a DMM human spine and an FGM intervertebral disc spacer are modelled and digitally fabricated for visualization and analysis in a VR environment. These studies show that the MMVP system is a practical tool for modelling, visualization, and subsequent fabrication of biomedical objects of discrete and functionally graded multi-materials for biomedical applications. The system may be adapted to control MMLM machines with appropriate hardware for physical fabrication of biomedical objects.
    Biofabrication 12/2009; 1(4):045001. DOI:10.1088/1758-5082/1/4/045001 · 4.29 Impact Factor
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