ABSTRACT
BACKGROUND: The major challenge of tissue engineering is to develop constructions with suitable properties which would mimic the natural extracellular matrix to induce the proliferation and differentiation of cells. Poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC), chitosan (CS), nano-silica (n-SiO₂) and nano-hydroxyapatite (n-HA) are biomaterials successfully applied for the preparation of 3D structures appropriate for tissue engineering. METHODS: We evaluated the effect of n-HA and n-SiO₂ incorporated PCEC-CS nanofibers on physical properties and osteogenic differentiation of human dental pulp stem cells (hDPSCs). Fourier transform infrared spectroscopy, field emission scanning electron microscope, transmission electron microscope, thermogravimetric analysis, contact angle and mechanical test were applied to evaluate the physicochemical properties of nanofibers. Cell adhesion and proliferation of hDPSCs and their osteoblastic differentiation on nanofibers were assessed using MTT assay, DAPI staining, alizarin red S staining, and QRT-PCR assay. RESULTS: All the samples demonstrated bead-less morphologies with an average diameter in the range of 190–260 nm. The mechanical test studies showed that scaffolds incorporated with n-HA had a higher tensile strength than ones incorporated with n-SiO₂. While the hydrophilicity of n-SiO₂ incorporated PCEC-CS nanofibers was higher than that of samples enriched with n-HA. Cell adhesion and proliferation studies showed that n-HA incorporated nanofibers were slightly superior to n-SiO₂ incorporated ones. Alizarin red S staining and QRT-PCR analysis confirmed the osteogenic differentiation of hDPSCs on PCEC-CS nanofibers incorporated with n-HA and n-SiO₂. CONCLUSION: Compared to other groups, PCEC-CS nanofibers incorporated with 15 wt% n-HA were able to support more cell adhesion and differentiation, thus are better candidates for bone tissue engineering applications.
Subject(s)
Humans , Biocompatible Materials , Bone and Bones , Cell Adhesion , Chitosan , Dental Pulp , Durapatite , Extracellular Matrix , Hydrophobic and Hydrophilic Interactions , Nanofibers , Nanoparticles , Osteoblasts , Silicon Dioxide , Spectroscopy, Fourier Transform Infrared , Stem Cells , Tensile Strength , Tissue EngineeringABSTRACT
The protective and anti-inflammatory effects of azo and azo-linked polymeric prodrugs of 5-aminosalicylic acid [5-ASA] on acetic acid induced colitis in rats were investigated. Three azo prodrugs; 4,4 -dihydroxy-azobenzene-3-carboxilic acid [azo compound I], 4-hydroxy-azobenzene-3,4-dicarboxilic acid [azo compound II], 4,4-dihydroxy-3-formyl-azobenzene-3-carboxylic acid [azo compound III] and their polyethylene glycol [PEG 6000] derivatives were synthesized. Rats were pretreated orally [1 hour prior to induction of colitis] with sulfasalazin [300 mg/kg], azo compounds I, II, III and polyethylene glycol conjugates of azo compounds II and III in doses which had the same amount of 5-ASA as sulfasalazin contains. The colonic damage was examined 24 hours later and characterized by gross microscopic injury and colonic edema. Among prodrugs only azo compound III [215 mg/kg] produced a significant [p<0.01] protective effect against colonic injury comparable with sulfasalazin. Doubling the dose [430 mg/kg] showed more anti-colitis effects. Polyethylene glycol conjugate of azo compounds II and III also showed reduction in the extent of the cell death and tissue disorganization similar to sulfasalazin. While neither sulfasalazin, nor azo compound II and its PEG polymer produced anti-edema effects, both azo compound III and its PEG polymer decreased colon edema significantly [p<0.05]. Histological examinations also indicated a marked reduction in tissue injury and inhibition in neutrophil infiltration in rats treated with azo compound III and PEG conjugates of azo compounds II and III. Results of this investigation provide experimental evidence supporting new cytoprotective, anti-inflammatory and anti-edema properties of the azo derivatives of 5-ASA and their PEGylated prodrugs