Refinement of Chitosan Composite Matrices to Ameliorate Bone Repair in a Mouse Calvarial Critical Bone Defect Model

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Bone regeneration by various methods has been researched to overcome serious clinical problems caused by large bone defects, including tissue engineering, biomaterials, stem cells and drug screening. Previously, we had developed the fabrication of a heparinized-chitosan membrane for the controlled release of BMP-2. The effect of this membrane on bone cells in vitro is promising; however, it has the disadvantage of being brittle, difficult to operate and not easy for cell attachment while using it as a barrier membrane for guided bone regeneration in vivo. Here we submit native chitosan to the Maillard reaction by co-heating a solution of glucose in order to improve the hydrophilicity of chitosan composite matrices. The optimized chitosan-glucose membranes will be surveyed their physical properties and biological activities in vitro. Moreover, we will investigate effects of the BMP-2-immobilizing heparinized-membranes on bone regeneration, using a critical-sized calvarial defect model. We hypothesize that the refined chitosan composite matrices can be used as an advanced barrier membrane to ameliorate bone repair in vivo animal model. Thus, the rationale and specific aims of the current project are outlined below: Specific aim 1: Fabrication, optimization and characterization of CSg films by the MR. We plan to submit native chitosan (CS) to the MR by co-heating a solution of glucose. The MR derivatives (CSg films) are surveyed and validated their superior physical properties to native CS films. We will explore the BMP-2 immobilizing effect of CSg films and Hep-CSg films and also examine the release profiles of BMP-2 from BMP-2/CSg films and BMP-2/Hep-CSg films. Specific aim 2: Understanding the biological activities of CSg films and Hep-CSg films. We plan to conduct an evaluation of biological activity (cytotoxicity, cell attachment, osteogenesis and mineralization, inflammation, antibacterial ability, etc.) of the optimized CSg films and Hep-CSg films in bone cells. Taken together, the best-optimized chitosan composite matrices (BMP-2/Hep-CSg films) can be suited to in vivo repair the CBDs. The BMP-2/Hep-CSg film should be a novel BM for GBR. Specific aim 3: Applying the best-optimized BMP-2/Hep/CSg films for in vivo GBR of CBDs. The developed novel BM is supposed to be osteoconductive and osteoinductive and can provide GBR for CBDs. After immobilizing BMP-2 at selected concentrations on the surface of Hep/CSg films, we will use the BMP-2/Hep-CSg film as a novel BM with an in situ controlled release system and apply it for in vivo GBR of CBDs. Qualitative and quantitative studies of new bone formation within the CBDs will be performed to understand the mechanism of induced bone healing. Anticipated results: We anticipate that the chitosan composite matrices refined by the MR have good physical and bioactivity properties and have the potential to be used as BMs for GBR of CBDs. BMP-2/Hep-CSg film is supposed to be both osteoconductive and osteoinductive and, therefore, is a promising biomaterial for bone tissue engineering. The developed novel BMs may have the potential to ameliorate bone repair and prevent bacterial invasion in dental and orthopaedic conditions.

Project IDs

Project ID:PC10607-0365
External Project ID:MOST106-2314-B182-012
Effective start/end date01/08/1731/07/18


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