The Preparation of Micro-Engineered Hydrogel Particles Using Microfluidic Technology and the Study of Its Application for Structurally-Controllable Cartilage Tissue Engineering

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

Project Details

Abstract

Articular cartilage has a limited capacity for self-repair after damage. Engineered cartilage is a promising treatment to replace or repair damaged tissue. However, attempts to develop engineered cartilage tissue for medical use have been a challenge. This is mainly due to the inferior control of the structure properties of the engineered tissue. In the traditional strategy for cartilage tissue engineering, scaffold material is seeded with cells and subsequently cultured in a bioreactor system. Cartilage tissue engineering based on this normally results in an, to some extent, un-controllable neo-tissue. This outcome may be attributable to un-uniform cell seeding, mass transfer limitation or other physical or biochemical conditions. To produce a tissue construct with structurally controllable property, the concept of using cell-entrapped micro-engineered hydrogel particles as constructing units to assemble a 3-D culture construct for in vitro tissue engineering is proposed in this research. This is different from the traditional way of tissue culture, which normally develops from the “bulk” point of view. The key advantages of the presented approach are the lower mass transfer limitation in the cell-entrapped micro-engineered hydrogel “clump”, due to the higher void volume in the cultured construct compared with tissue engineering using an intact construct. This may contribute to the formation of a more homogenous neo-tissue. Besides, the inner structure of a 3-D culture construct can be tailored by piling up cell-entrapped micro-engineered hydrogel particles with varied entrapped cell density (or extracellular matrix) to create differential structures in a neo-tissue. On the other hand, to generate the cell-entrapped micro-engineered hydrogel particles for the application of this kind, a microfluidic system capable of performing micro-entrapment of cells with high uniformity of particle size will be developed in this project. Compared with the existing devices for the similar purpose of this kind, the proposed microfluidic system not only can provide a simple and sterile route but also a cell-friendly way to carry out micro-entrapment of cells. To test the feasibility of whole ideas, a microfluidic system suitable for this application will be developed in the first year project. The generated cell-entrapped micro-engineered hydrogel particles will be evaluated in terms of size, particle size distribution, uniformity of entrapped cell number and cell viability. Also, the optimum particle size range will be determined by perfusion cell culture experiment to find out the one with higher cellular metabolic activity (less mass transfer limitation). In the second year project, research will focus on using the cell-entrapped micro-engineered hydrogel particles for cartilage tissue engineering to explore (1) if the presented approach can create a more homogenous neo-tissue and (2) whether the pre-cultured cell-contained micro-engineered hydrogel particles or the freshly generated particles is suitable in terms of forming a more structurally integrated neo-tissue. Finally, to justify that the presented strategy can produce structurally controllable neo-tissue with differential structures in it, micro-engineered hydrogel particles with varied entrapped cell density will be use to assemble a 3-D culture construct for long-term perfusion culture and the resulting properties of the engineered tissue will be evaluated. As a whole, one can vision that the ultimate hope beyond this fundamental research is to use the cell (and/or growth factors)-entrapped micro-engineered hydrogel particles for in vitro structurally controllable cartilage tissue engineering or even to fill up the defect size of cartilage injury (e.g. using injection method) instead of implanting an intact in vitro engineered cartilage tissue, which may avoid the highly invasive surgical procedures and the resulting long rehabilitation process.

Project IDs

Project ID:PB9808-2378
External Project ID:NSC98-2221-E182-008
StatusFinished
Effective start/end date01/08/0931/07/10

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