[9] a)B.Gates,Y.Yin,Y.Xia, Chem. Mater. 1999, 11,2827.b)S.A.Johnson, P. J. Olivier, T. E. Mallouk, Science 1999, 283, 963. c) P. Jiang, J. Cizeron, J. F.Bertone,V. L.Colvin, J. Am. Chem. Soc. 1999, 121,11630.d)T.Cas- sagneau, F. Caruso, Adv. Mater. 2002, 14, 34. e) D. Wang, F. Caruso, Adv. Mater. 2001, 13, 353. f) M. Deutsch, Y. A. Vlsov, D. J. Norris, Adv. Mater. 2000, 12,1176. [10] Z.Zhong,Y.Yin,B.Gates,Y.Xia, Adv. Mater. 2000, 12,206. [11] N. G. R.Broderick,G. W.Ross,H. L.Offerhause,D. J.Richardson,D. C. Hanna, Phys. Rev. Lett. 2000, 84,4345. [12] a) G. Decher, J. D. Hong, Makromol. Chem. Macromol. Symp. 1991, 46, 321.b)G.Decher, Science 1997, 277,1232. [13] a) F. Caruso, R. A. Caruso, H. Möhwald, Science 1998, 282, 1111. b) E. Donath, G. B. Sukhorukov, F. Caruso, S. A. Davis, H. Möhwald, Angew. Chem. Int. Ed. 1998, 37,2201. [14] For reviews, see: a) F. Caruso, Chem. Eur. J. 2000, 6, 413. b) F. Caruso, Adv. Mater. 2001, 13,11. [15] F. Caruso, H Lichtenfeld, E. Donath, H. Möhwald, Macromolecules 1999, 32,2317. [16] a) G. Kumaraswamy, A.M. Dibaj, F. Caruso, Langmuir 2002, 18, 4150. b)Z.Liang,A.S.Susha,F.Caruso, Adv. Mater. 2002, 14,1160. [17] It has been reported that the stoichiometry of lithium niobate is depen- dent on the Li:Nb molar ratio of the precursors used. Using LiN- b(OC 2 H 5 ) 6 withaLi:Nbmolarratioof1:1asaprecursorleadsdominantly toLiNbO 3 (S.Hirano,K.Kato, J. Non-Cryst. Solids 1988, 100,538). [18] H.Fan,Y.Zhou,P.Lopez, Adv. Mater. 1997, 9,728. [19] a) D. Wang, F. Caruso, Chem. Mater. 2002, 14, 1909. b) D. Wang, R. A. Caruso,F.Caruso, Chem. Mater. 2001, 13,364. [20] K.Furusawa,W.Norde,J.Lyklema, Kolloid Z. Z. Polymer 1972, 250,908. [21] H.Riegler,M.Engel, Ber. Bunsen-Ges. 1991, 95,1424. [22] N. D.Denkov,O. D.Velev,P. A.Kralchevsky,I. B.Ivanov,H.Yoshimura, K.Nagayama, Langmuir 1992, 8,3183. Porous Polymer and Cell Composites That Self-Assemble In Situ** By Aliasger K. Salem, Felicity R. A. J. Rose, Richard O. C. Oreffo, Xuebin Yang, Martyn C. Davies , John R. Mitchell, Clive J. Roberts , Snjezana Stolnik-Trenkic, Saul J. B. Tendler, Phil M. Williams , and Kevin M. Shakesheff* An aim of tissue engineering is to regenerate tissues within a patient by delivering specific cells to a site of damage and then triggering their proliferation and differentiation. [1] Ex- amples of such applications include stem cell delivery to the spinal cord, [2] bone defects, [3] and the pancreas. [4] A delivery vehicleisrequiredforthecellsthatcanfillthedamagedspace withinthebodyandsupplysignalstocells.Ideally,thevehicle would have similar properties to the porous scaffolds that have proven successful in ex vivo regeneration of tissues such as cartilage, [5] bone, [6] and liver. [7] Here we report a new porous scaffold that can be delivered by syringe into a tissue or cavity as a polymer and cell slurry. Immediately following delivery, the slurry self-assembles into a porous scaffold with cells distributed throughout. Self-assembly involves the cross- linking of polymer particles by a mechanism that does not interferewithcellfunction. In broad terms, tissue engineering scaffolds are either pre- formed water-insoluble matrices, with large interconnected pores within which cells are seeded, or hydrogels that solidify around the cell population. [8,9] The matrix scaffold is formed before cells are seeded and then it is either placed in a bio- reactor for in vitro tissue formation or implanted into a patient for augmented in vivo tissue regeneration. Whilst the three-dimensional cell culture environment within these po- rous scaffolds is favorable to tissue regeneration, the need to preform the scaffold before seeding and implantation is prob- lematic. Cell seeding methods can be inefficient due to poor transport of the cells through the matrix and cell damage. In terms of implantation, the scaffold must be shaped to fill a cavity within the body, requiring knowledge of the cavity di- mensions and an invasive operation. In contrast, a number of hydrogel materials have been designed that can be delivered directly into the body through a syringe. The gel forms within thebodyfollowingatriggersignal,forexampleatemperature change or UV light exposure. [10,11] Such systems have the advantagethattheycanfillcavitiesofanyshapewithoutprior knowledge of the cavity dimensions. However, such hydrogels lack large interconnected porous networks and, hence, tissue formation is limited by the barrier of diffusion to signaling andnutrientmolecules. Our novel material possesses features of both porous ma- trices and in situ forming gels to generate porous scaffolds thatself-assembleatthesiteofinjection,entrappingthedeliv- ered cells without compromising viability. Figure 1 is a sche- matic representation of the process of scaffold self-assembly. We start with particles of poly(lactic acid)-poly(ethylene gly- 210 Ó 2003WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim 0935-9648/03/0302-0210$17.50+.50/0 Adv. Mater. 2003, 15,No.3,February5 COMMUNICATIONS ± [*] Prof. K. M. Shakesheff,Dr. A. K. Salem,Dr. F. R. A. J. Rose, Prof. M. C. Davies,Dr. C. J. Roberts,Dr. S. Stolnik-Trenkic, Prof. S. J. B. Tendler,Dr. P. M. Williams SchoolofPharmaceuticalSciences,TheUniversityofNottingham NottinghamNG72RD(UK) E-mail: kevin.shakesheff@nottingham.ac.uk Dr. R. O. C. Oreffo,X. Yang UniversityOrthopaedics,UniversityofSouthampton GeneralHospital,SouthamptonSO166YD(UK) Prof. J. R. Mitchell SchoolofBiologicalSciences,TheUniversityofNottingham NottinghamNG72RD(UK) [**] TheauthorsacknowledgetheBBSRCandEPSRCforsupport. Self-assembly of scaffold Binding Avidin Biotin gr oup Biotinylated PLA -PEG microparticl e Self-assembly of scaffold Binding Avidin Biotin gr oup Biotinylated PLA -PEG microparticl e In presence of cell suspens ion Fig. 1.Aschematicrepresentationofscaffoldself-assembly.