Poly(lactic-co-glycolic acid) enhances maturation of human monocyte-derived dendritic cells Mutsumi Yoshida, Julia E. Babensee Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, Georgia 30332 Received 10 May 2004; accepted 28 May 2004 Published online 13 August 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.a.30131 Abstract: Immature dendritic cells (iDCs) were derived from human peripheral blood monocytes, and treated with 75:25 poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) or film to assess the resultant dendritic cell (DC) maturation as compared to positive control of lipopolysac- charide (LPS) treatment for DC maturation or negative con- trol of untreated iDCs. The effect of PLGA contact on DC maturation was examined as one possible explanation for the PLGA adjuvant effect we have observed in the enhance- ment of an immune response to codelivered model antigen, as adjuvants act through the maturation of DCs. Culturing iDCs with PLGA MPs or PLGA film resulted in morphology similar to that of LPS-matured DCs and the association, or possible internalization, of PLGA MPs. Furthermore, bioma- terial-treated iDCs demonstrated an increase in MHC class II and costimulatory molecule expression compared to iDCs but to a lower level than that of LPS-matured DCs. Direct iDC contact with PLGA MPs was necessary for maturation. Immature DCs exposed to PLGA MPs were stimulatory of allogeneic T-cell proliferation, whereas cells exposed to PLGA film were not. Further, PLGA MPs supported a mod- erate delayed type hypersensitivity reaction in mice indica- tive of in vivo DC maturation. Taken together, these results suggest that PLGA is a DC maturation stimulus and that the form of the biomaterial may influence the extent of DC maturation. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 45–54, 2004 Key words: poly(lactic-co-glycolic acid); dendritic cells; ad- juvant INTRODUCTION Tissue engineering has become an attractive ap- proach for the development of functional tissue or organ substitutes where no suitable alternative exists or to reduce morbidity associated with current proce- dures. Success of such engineered constructs depends on the viability of functional cells and the physiolog- ical integration of the device into the host living sys- tem. As such, implanted tissue-engineered devices must not only be accepted by the host immune system but also elicit minimal inflammation to avoid replace- ment of the seeded cells with, or formation of, exces- sive fibrotic or granulation tissue. The response against an implanted tissue-engineered device may be comprised of a specific immune response against the cellular component, similar to transplanted organ al- lograft or xenograft rejection depending on the cell source, as well as a nonspecific inflammatory response against the biomaterial component of the device. 1 While encapsulation and other immunoisolation strat- egies were originally developed to prevent the detec- tion of the implanted cells by host immune surveil- lance, antigens or other cellular components shed or secreted from the implanted cells may escape through the membrane, resulting in indirect recognition by the host immune cells and immune stimulation. 2 This rec- ognition and the ensuing immune stimulation may be intensified by the presence of a biomaterial compo- nent through induction of an innate immune response, recruiting antigen presenting cells (e.g., macrophages and dendritic cells) and inducing their activation, which would lead to the enhancement of the adaptive response. 3 In this way, the biomaterial component can act as an adjuvant in the immune response towards associated shed cell antigens from a tissue-engineered construct. 3 The elevation of specific immune response against the antigens associated with the device will lead to compromised effectiveness or failure of the device. 1 While a polymer often used in tissue engi- neering, poly(lactic-co-glycolic acid) (PLGA), acted as an adjuvant in the enhancement of the humoral re- Correspondence to: Julia E. Babensee; e-mail: julia.babensee@ bme.gatech.edu Contract grant sponsor: National Science Foundation; contract grant number: BES-0239152 Contract grant sponsor: Arthritis Foundation. © 2004 Wiley Periodicals, Inc.