gregation of aerosols following their delivery from an inhaler 1997元. Overcoming cellular barriers esents whe to helpthe delivery syteTo chicve 988225K 5um rysystem must overcome Figure 6.Scanning electron micrograph of a large porous aerosol particle. (2)The particle must be endocytosed or taken up by a cell aredetoor patients dying of liver failure who that can be implanted in the body.The macr sules als act as an imn ha wn to complex 、2001 Another exan the work of Putam and Co-Wo ers who na (Putnam et al ause the c n is water Materials for Tissue Engineering alginates can be ion ked by div te ways which materials have been shown ment of dia (1The materials are able to induce cellular migration or been can and act as be ionicall wpot con an 990)Interestingly Sefton and co-workers have shown that hey can even er Lahooti nd Seftor 2000) ale anization.One of the most widely This has taken place n on of three forms The first is (a e of the materials te cell tructs nte for trea orm appr s type (rticas or th cre AIChE Journal December 2003 Vol.49.No.12 2997gregation of aerosols following their delivery from an inhaler. A variety of groups are developing improved inhalers Schus- Ž ter et al., 1997 . At the same time, new materials designs are . being used to develop better aerosols. One widely used ap￾proach involves lowering the density of the aerosol particles while increasing their porosity and size Figure 6 . By doing Ž . this, aerosol aggregation is greatly reduced. In addition be￾cause these particles are larger than conventional aerosols, they are less likely to be taken up by lung macrophages and as such are able to prolong the release of drugs such as in￾sulin in animal models for up to four days Edwards et al., Ž 1997 .. O©ercoming cellular barriers Gene therapy represents an area where polymers can be used to help drugs overcome cellular barriers. To achieve successful gene therapy, the delivery system must overcome a variety of different barriers, as follows: Ž . 1 It is important to be able to condense DNA to a rea￾sonably small particle. Ž . 2 The particle must be endocytosed or taken up by a cell. Ž . 3 It must then be taken up by the cells endosome. Ž . 4 It must release the DNA in active form. Ž . 5 It must be transferred to the cell’s nucleus. There have been a number of classical materials that have been used for gene therapy. Some examples are lipids, such as lipofectamine, liposomes, and various polymers, like polyethylenenimine. An interesting new type of system that has been developed by Davis and co-workers is cationic cy￾clodextrins. These have been shown to complex with DNA to form small particles that have shown to be useful in a variety of in ®i®o and in ®itro studies Davis, 2001 . Another example Ž . is the work of Putnam and co-workers who have modified polylysine to form novel polycationic polymers by precisely balancing the structure of side-chain termini to the polymer Ž . Putnam et al., 2001 . Materials for Tissue Engineering There are three ways in which materials have been shown to be useful in tissue engineering: Ž . 1 The materials are able to induce cellular migration or tissue regeneration. Ž . 2 The materials are used to encapsulate cells and act as an immunoisolation barrier. Ž . 3 The materials are used as a matrix to support cell growth and cell organization. An example of the first approach involves the use of gly￾cosaminoglycanrcollagen constructs that stimulates healing and act as an artificial skin. This type of approach has also been used in nerve regeneration and cartilage regeneration Ž . Yannas et al., 1982 . In the second case, cells are encapsu￾lated in a polymer which acts an immunoisolation barrier. This has taken place in one of three forms. The first is aŽ . hollow fiber membranes where the cells are connected to the body. Some of the materials used are polysulfone mem￾branes. This type of approach is in clinical trials for treating patients with liver failure by using porcine hepatocytes in the hollow fibers. These types of systems are being explored as a Figure 6. Scanning electron micrograph of a large porous aerosol particle. ‘‘bridge to transplant,’’ for patients dying of liver failure who are urgently waiting for a transplant Hubbell and Langer, Ž 1995 . This type of approach has also been explored for im- . plantable systems containing beta cells for treating diabetes Ž . Ž. Sullivan et al., 1991 . The second form is b macrocapsules that can be implanted in the body. The macrocapsules also act as an immunoisolation barrier to prevent immune cells from entering the cellular transplant, but can allow medium or small sized molecules to penetrate through. One of the materials that has often been used for these applications are polyacrylonitrile-polyvinylchloride PAN-PVC membranes. Ž . These systems have been in clinical trials for treating certain brain diseases, for example, for releasing pain medication into the brain Aebischer et al., 1991 . The third are c microcap- Ž . Ž. sules can keep the cells viable. The most widely studied sys￾tem has been alginates which have the advantage of being able to encapsulate cells because the encapsulation is water based and the alginates can be ionically cross-linked by diva￾lent ions such as calcium ions. This type of approach was originally pioneered by Lim and Sun in the treatment of dia￾betes in animal studies Lim and Sun, 1980 . Synthetic poly- Ž . mers have also been explored. For example, novel polyphosp￾hazenes have been synthesized that can be ionically crosslinked in the presence of cells and water Cohen et al., Ž 1990 . Interestingly, Sefton and co-workers have shown that . they can even encapsulate mammalian cells in viable form using polymers in organic solvents Uludag and Sefton, 1993; Ž Lahooti and Sefton, 2000 .. The third type of approach involves using a polymer matrix to act as a scaffold to enable cellular proliferation and reor￾ganization. One of the most widely used scaffolds has been lacticrglycolic acid copolymers. In this case the lacticrglycolic acid copolymers are formed into fibrous systems or foams in desired anatomical shapes Mikos et al., 1993; Mooney et al., Ž 1995; Shastri et al., 2000 Figure 7 and Figure 8 . The cells .Ž . are placed on them and are allowed to grow and organize to form appropriate cellular constructs. This type of approach has already been used in the creation of artificial skin Ž . Hansbrough et al., 1992 and is in clinical trials for the cre￾AIChE Journal December 2003 Vol. 49, No. 12 2997