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.
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.
"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 . Briefly, PLGA was added with a powder weight to solution volume of 13:100 in organic solvent 1.4-dioxane. "
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Phytomolecules may chemically bind to scaffold materials for medical applications. The present study used an osteoconductive porous poly(l-lactide-co-glycolide)/tricalcium phosphate (PLGA/TCP) to incorporate an exogenous phytoestrogenic molecule icaritin to form a PLGA/TCP/icaritin composite scaffold material with potential slow release of icaritin during scaffold degradation. Accordingly, the present study was designed to investigate its in vitro degradation characteristics and the release pattern of icaritin at three different doses (74 mg, 7.4 mg and 0.74 mg per 100 g PLGA/TCP, i.e. in the PLGA/TCP/icaritin-H, -M and -L groups, respectively). A PLGA/TCP/icaritin porous composite scaffold was fabricated using a computer-controlled printing machine. The PLGA/TCP/icaritin scaffolds were incubated in saline at 37 °C for 12 weeks and the pure PLGA/TCP scaffold served as a control. During the 12 weeks in vitro degradation, the scaffolds in all four groups showed changes, including a decrease in weight, volume and pore size of the composite scaffold, while there was a decrease in acidity and an increase in Ca and lactic acid concentrations in the degradation medium, especially after 7 weeks. The rate of degradation was explained by the relationship with the content of icaritin incorporated into the scaffolds. The higher the icaritin content in the scaffolds, the slower the degradation could be observed during 12 weeks. After 12 weeks, the SEM showed that the surface of the PLGA/TCP and PLGA/TCP/icaritin-L groups was relatively smooth with a gradual decrease in number and size of the micropores, while the porous morphology on the surface of the PLGA/TCP/icaritin-M and PLGA/TCP/icaritin-H groups was partly maintained, accompanied by a decrease in phosphate (P) and calcium (Ca) contents at the surface. Though the mechanical property of the PLGA/TCP/icaritin scaffold decreased after degradation, its porous structure was maintained, which was essential for cell migration and ingrowth of newly regenerated tissues in vivo. The controlled release of icaritin from the composite scaffold reached about 70% of the incorporated icaritin into the degradation medium after 12 weeks. The above findings suggested that the structural and degradation properties of the porous composite PLGA/TCP/icaritin scaffold were dependent on icaritin concentrations. This innovative composite porous scaffold material developed in the present study may be used as a good scaffold material for enhancing bone repair, especially at high concentrations of icaritin. In vivo confirmation is, however, needed to substantiate our in vitro findings.
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