Biodegradable Polymeric Microcarriers with Controllable Porous Structure for Tissue Engineering Xudong Shi, Lei Sun, Jian Jiang, Xiaolin Zhang, Wenjun Ding, Zhihua Gan* Introduction In recent decades, tissue engineering has gained increasing attention because of its significant medical applications in restoring, maintaining, or improving functions for injured tissues or organs. [1] To create a new tissue, an increasingly attractive strategy is to implant cell-attached scaffolds into a patient’s body for the direct formation of new tissue. [2,3] For the fabrication of cell-attached scaffolds, microcarriers are one of the best candidates for the cultivation of anchorage-dependent animal cell lines. [4] An important advantage of this technology is that the cell-seeded microcarriers can be injected directly into defect sites of patients, which can minimize incision during the trans- plantation process. [5,6] Since the first introduction by Van Wezel in 1967, microcarrier cultures have shown distinct advantages for the mass production of cells, such as offering a large surface to save space and cost, better simulation of complex biological processes, convenience for suspension of culture, and enhancing the phenotype expression of cells. [7–12] However, the use of microcarrier culture techniques in tissue engineering has only been explored to a limited extent up to now because of some residual problems such as the difficulty to separate cells from microcarriers. [5] Therefore, a biocompatible microcarrier with a suitable biodegradation rate is preferred to keep sufficient in vivo longevity for cell seeding and to avoid the cell separation step because of its complete biodegradability in vivo. Aliphatic polyesters with good flexibility in composition, structure, and property are promising candidates for the Full Paper X. Shi, Z. Gan The CAS Key Laboratory of Engineering Plastics, Joint Laboratory of Polymer Science and Materials, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China Fax: þ86-10-62529194; E-mail: zhgan@iccas.ac.cn L. Sun, J. Jiang Beijing Institute of Traumatology and Orthopeadics, Beijing 100035, P. R. China X. Zhang, W. Ding The Graduate School of Chinese Academy of Sciences, Beijing 100049, P. R. China Porous microspheres fabricated by biodegradable polymers show great potential as micro- carriers for cell cultivation in tissue engineering. Herein biodegradable poly(DL-lactide) (PLA) was used to fabricate porous microspheres through a modified double emulsion solvent evaporation method. The influence of fabrication parameters, such as the stirring speed of the primary and secondary emulsion, the polymer concentration of the oil phase, and solvent type, as well as the post-hydrolysis treatment of the porous structure of the PLA microspheres are dis- cussed. Good attachment and an active spread of MG-63 cells on the microspheres is observed, which indicates that the PLA microspheres with controllable porous structure are of great poten- tial as cell delivery carriers for tissue engineering. Macromol. Biosci. 2009, 9, 1211–1218 ß 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim DOI: 10.1002/mabi.200900224 1211