Poly(e-Caprolactone) and Poly (L-Lactic-Co-Glycolic Acid) Degradable Polymer Sponges Attenuate Astrocyte Response and Lesion Growth in Acute Traumatic Brain Injury DARICE Y. WONG, 1 SCOTT J. HOLLISTER, 1–3 PAUL H. KREBSBACH, 4 and CHRISTOPHER NOSRAT 4,* ABSTRACT This study evaluated the response of rat brain to 2 degradable polymers (poly (L-lactic-co-glycolic acid) (PLGA), and poly(e-caprolactone) (PCL)), two common materials in tissue engineering. PLGA has been extensively studied in the brain for controlled drug release as injectable microspheres and is generally accepted as biocompatible in that capacity. Biocompatibility in other forms and for different functions in the brain has not been widely studied. PCL was chosen as an alternative to PLGA for its slower degradation and less-acidic pH upon degradation. Porous scaffolds were made from both polymers and implanted into rat cerebral cortex for 1 and 4 weeks. Morphology, defect size, activation of microglia (OX-42) and as- trocytes (glial fibrillary acidic protein (GFAP)), infiltration of activated macrophages (major histocompat- ibility complex ( MHC)-II), and ingrowth of neurons (b-tubulin type III (Tuj-1)) and progenitor cells (nestin) were analyzed using hematoxylin and eosin staining and immunofluorescence. PCL induced a lower in- flammatory response than PLGA, as demonstrated by lower MHC-II and GFAP expression and greater ingrowth. Both polymers alleviated astrocytic activation and prevented enlargement of the defect. Tuj-1-, nestin-, and GFAP-positive cells were observed growing on both polymers at the peripheries of the sponge implants, demonstrating their permissiveness to neural ingrowth. These findings suggest that both poly- mers attenuate secondary death and scarring and that PCL might have advantages over PLGA. INTRODUCTION B RAIN LESIONS can result from a range of causes, from traumatic injury to disease. The resultant voids are un- able to retain or support injections of suspension treatments such as cells 1 or growth factors, which disperse quickly and lose effectiveness. From a tissue-engineering standpoint, a delivery vehicle that fills the void and contains drugs, neu- rotrophic factors, or cells has the potential to localize and maintain these treatments in the implant site, increasing the effectiveness, and provide a path toward repair and recon- stitution of the lost parenchyma that is lacking in current clinical treatments. 2 This delivery vehicle must satisfy cer- tain design criteria, such as permissiveness to neural cell growth and immunological compatibility. Such scaffolds should not cause significant inflammatory responses that may exacerbate the injury. Also, mechanically, the material must be close enough to the tissue dynamics that surgical insertion and normal movements of the patient do not cause more physical damage. Treatment strategies for brain injuries such as hypoxic ischemia models focus mainly on combination treatments Departments of 1 Biomedical Engineering, 2 Mechanical Engineering, 3 Neurosurgery, and 4 Biologic and Materials Sciences, Uni- versity of Michigan at Ann Arbor, Ann Arbor, Michigan. *Current affiliation: University of Tennessee Health Science Center, College of Dentistry, Cancer Research Building, Memphis, Tennessee. TISSUE ENGINEERING Volume 13, Number 10, 2007 # Mary Ann Liebert, Inc. DOI: 10.1089/ten.2006.0440 2515