ABSTRACT
A biocompatible hydrogel of poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) which includes the cell-adhesive region of fibronectin Arg-Gly-Asp was synthesized and its structure, rheological and dielectric properties were characterized. The ability of a PHPMA-RGD hydrogel to promote tissue regeneration and support axonal outgrowth in the injured adult and developing rat spinal cord was evaluated. The structure of the PHPMA-RGD hydrogel displayed an interconnected porous structure, with viscoelastic properties similar to those of the neural tissue, and conductivity properties due to a peptide group. The polymer hydrogel provided a structural, three-dimensional continuity across the defect, facilitating the migration and reorganization of local wound-repair cells, as well as tissue development within the lesion. Angiogenesis and axonal growth also occurred within the microstructure of the tissue network, and supraspinal axons migrated into the reconstructed cord segment. In addition, the hydrogel induced a reduction of necrosis and cavitation in the adjacent white and gray matter. These polymer hydrogel matrices therefore display the potential to repair tissue defects in the central nervous system by enhancing the development of a tissue equivalent as well as axonal growth across the reconstructed lesion.
Subject(s)
Biocompatible Materials , Polymethacrylic Acids , Spinal Cord Injuries/therapy , Animals , Animals, Newborn , Biocompatible Materials/chemistry , Female , Hydrogels , Materials Testing , Microscopy, Electron , Microscopy, Electron, Scanning , Nerve Regeneration , Oligopeptides , Polymethacrylic Acids/chemistry , Rats , Rats, Sprague-Dawley , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathologyABSTRACT
Ability of molecular complexes of [Doxorubicin (DX)-cyclodextrin (Cd)] to enhance the anticellular activity of antineoplastic drug Doxorubicin and to reverse its multidrug resistance has been investigated. A spectroscopic study of the alpha, beta, and gamma-[DX-Cds] complexes has been investigated in relation to their biological effects on a multidrug resistant (MDR) human rectal adenocarcinoma cell line (HRT-18). A ten fold enhancement of DX anticellular activity in presence of beta-cyclodextrin alone was detected.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Cyclodextrins/chemistry , Cyclodextrins/pharmacokinetics , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Cell Survival , Circular Dichroism , Drug Resistance, Multiple , Humans , Models, Chemical , Spectrometry, Fluorescence , Time Factors , Tumor Cells, CulturedABSTRACT
A biocompatible heterogeneous hydrogel of poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) showing an open porous structure, viscoelastic properties similar to the neural tissue and a large surface area available for cell interaction, was evaluated for its ability to promote tissue repair and axonal regeneration in the transected rat spinal cord. After implantation, the polymer hydrogel could correctly bridge the tissue defect, from a permissive interface with the host tissue to favour cell ingrowth, angiogenesis and axonal growth occurred within the microstructure of the network. Within 3 months the polymer implant was invaded by host derived tissue, glial cells, blood vessels and axons penetrated the hydrogel implant. Such polymer hydrogel matrices which show neuroinductive and neuroconductive properties have the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost of tissue.
