Antibacterial Wound Healing Gels from Oligochitosan Salts

Oligochitosan salt-based antibacterial wound gels were developed and evaluated in both in vitro and in vivo models. The antibacterial activities of the oligochitosan salts and the wound gels were investigated against Staphylococcus epidermidis RP625 and Escherichia coli ATCC 11775. The minimum inhibitory concentrations (MIC) of the oligochitosan salts were found in the range of 16-256 μg/mL. The wound gels demonstrated their in vitro activities on inhibiting the growth of bacteria. The 3-D collagen gel matrix containing human dermal fibroblasts cultured with each test gel was used as an in vitro model for the examination of cell proliferation and secretion of interleukin-8 (IL-8). The gels appeared to promote the proliferation and formation of cellular process of the fibroblasts in the 3-D collagen gels and stimulate the fibroblasts to produce more IL-8. In the in vivo model, it was noted that the gels could accelerate the wound closure process. The wounds were completely closed within 14 days.

Loss of PALS1 Expression Leads to Tight Junction and Polarity Defects

Prior work in our laboratory established a connection between the PALS1/PATJ/CRB3 and Par6/Par3/aPKC protein complexes at the tight junction of mammalian epithelial cells. Utilizing a stable small interfering RNA expression system, we have markedly reduced expression of the tight junction-associated protein PALS1 in MDCKII cells. The loss of PALS1 resulted in a corresponding loss of expression of PATJ, a known binding partner of PALS1, but had no effect on the expression of CRB3. However, the absence of PALS1 and PATJ expression did result in the decreased association of CRB3 with members of the Par6/Par3/aPKC protein complex. The consequences of the loss of PALS1 and PATJ were exhibited by a delay in the polarization of MDCKII monolayers after calcium switch, a decrease in the transepithelial electrical resistance, and by the inability of these cells to form lumenal cysts when grown in a collagen gel matrix. These defects in polarity determination may be the result of the lack of recruitment of aPKC to the tight junction in PALS1-deficient cells, as observed by confocal microscopy, and subsequent alterations in downstream signaling events.