The interrelationships of the gut microbiome and inflammation in colorectal carcinogenesis.

The cause of colorectal cancer (CRC) is multifactorial, with genetic, molecular, inflammatory, and environmental risk factors. Recently, the gut microbiota has been recognized as a new environmental contributor to CRC in both animal models and human studies. An additional interplay of the gut microbiome with inflammation is also evident in studies that have shown that inflammation alone or the presence of bacteria/bacterial metabolites alone is not enough to promote tumorigenesis. Rather, complex interrelationships with the gut microbiome, inflammation, genetics, and other environmental factors are evident in progression of colorectal tumors.

Biomimetic tissue-engineered anterior cruciate ligament replacement.

There are >200,000 anterior cruciate ligament (ACL) ruptures each year in the United States, and, due to the poor healing properties of the ACL, surgical reconstruction with autograft or allograft tissue is the current treatment of these injuries. To regenerate the ACL, the ideal matrix should be biodegradable, porous, and exhibit sufficient mechanical strength to allow formation of neoligament tissue. Researchers have developed ACL scaffolds with collagen fibers, silk, biodegradable polymers, and composites with limited success. Our group has developed a biomimetic ligament replacement by using 3D braiding technology. In this preliminary in vivo rabbit model study for ACL reconstruction, the histological and mechanical evaluation demonstrated excellent healing and regeneration with our cell-seeded, tissue-engineered ligament replacement.

Evaluation of the anterior cruciate ligament, medial collateral ligament, achilles tendon and patellar tendon as cell sources for tissue-engineered ligament.

This study investigated four different connective tissue cell types to determine which cell type should be the source for seeding a tissue-engineered anterior cruciate ligament (ACL) replacement. Cells derived from the ACL, medial collateral ligament (MCL), achilles tendon (AT), and patellar tendon (PT) of New Zealand White rabbits were isolated and cultured. Each cell type was cultured in vitro after seeding on three-dimensional (3-D) braided polymer scaffolds and on tissue culture polystyrene that served as a control. Samples were evaluated and compared for their morphology, proliferation, and gene expression of fibronectin, type I and type III collagen. Scanning electron microscopy (SEM) photomicrographs verified cell attachment of all four types of connective tissue fibroblasts to the scaffolds. Preliminary results comparing proliferation indicate that cells obtained from the PT and AT have the fastest proliferation. Whereas gene expression of the phenotypic markers measured using real-time reverse transcription polymerase chain reaction (RT-PCR) indicates ACL cells have the highest gene expression for the matrix markers. This leads to the question of which cell type should be the cell source for tissue-engineering of ligament, the highly proliferating cells or the differentiated matrix producing cells. This study would suggest that ACL differentiated matrix producing cells are the most suitable cells for further study and development of a tissue-engineered ligament.

Short exposure time sensitivity of white cells to shear stress.

White cells are a critical functional element circulating in blood. This study sheared fresh whole bovine blood in stainless steel and polymeric capillary tubes of various lengths and diameters. Flow rate was constant, resulting in a range of exposure times and shear stresses. White cell count, cell integrity (trypan blue exclusion), and phagocytic index (latex bead ingestion) were assayed. It was found that cell function declined at lower stresses than cell count. White cell count was maintained at higher stress levels at the short exposure times used here compared with the published results at longer times. This study suggests that function, not count, is the critical parameter when studying shear effects on white cells, and that, like red cells, there may be an exposure time effect and that white cell function is impacted at stresses lower than are required for hemolysis.