The pore size of polycaprolactone scaffolds has limited influence on bone regeneration in an in vivo model

Bone tissue engineering scaffolds should be designed to optimize mass transport, cell migration, and mechanical integrity to facilitate and enhance new bone growth. Although many scaffold parameters could be modified to fulfill these requirements, pore size is an important scaffold characteristic that can be rigorously controlled with indirect solid freeform fabrication. We explored the effect of pore size on bone regeneration and scaffold mechanical properties using polycaprolactone (PCL) scaffolds designed with interconnected, cylindrical orthogonal pores. Three scaffold designs with unique microarchitectures were fabricated, having pore sizes of 350, 550, or 800 Μm. Bone morphogenetic protein-7 transduced human gingival fibroblasts were suspended in fibrin gel, seeded into scaffolds, and implanted subcutaneously in immuno-compromised mice for 4 or 8 weeks. We found that (1) modulus and peak stress of the scaffold/bone constructs depended on pore size and porosity at 4 weeks but not at 8 weeks, (2) bone growth inside pores depended on pore size at 4 weeks but not at 8 weeks, and (3) the length of implantation time had a limited effect on scaffold/bone construct properties. In conclusion, pore sizes between 350 and 800 Μm play a limited role in bone regeneration in this tissue engineering model. Therefore, it may be advantageous to explore the effects of other scaffold structural properties, such as pore shape, pore interconnectivity, or scaffold permeability, on bone regeneration when designing PCL scaffolds for bone tissue engineering. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64538/1/32381_ftp.pd

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine