Development of bioactive, porous scaffolds for the vascularization of engineered tissues.

摘要

The lack of vascular networks to support the growth, function, and survival of three-dimensional tissues represents one of the greatest challenges of tissue engineering today. This thesis project was designed to constitute the first part of a work whose final objective is the creation of functional micro-vessel networks within three-dimensional scaffold constructs for tissue engineering. Specifically, this part was aimed at creating functional scaffolds, that may be used in the continued studies towards achieving this long-term goal.; As a first step, three co-polymers on the form poly(epsilon-caprolactone-co- D,L-lactic acid)-poly(ethylene glycol)-poly(epsilon-caprolactone-co-D,L-lactic acid) were synthesized to provide mechanically stable biomaterials with controllable and tunable material properties. To achieve this, the monomer content in the side chains was varied and the resulting co-polymers were characterized using 1H-NMR, GPC, DSC, WAXS, and DMA*. Furthermore, the hydrolytic degradation profiles of samples fabricated from melt-pressed films were studied over six months, as well as the influence of degradation on tensile strength. Based on obtained results and observations, two of the co-polymers were judged suitable, in terms of mechanical integrity and degradation profile, for further investigation.; To improve cell/polymer interactions, co-polymer films were modified by protein immobilization using imidoester chemistry. The effect of several protein preparations on smooth muscle cell (SMC) adhesion and proliferation was studied over six days in culture. Cells were counted at pre-set intervals, and further analyzed by scanning electron microscopy and fluorescent labelling of the differentiation marker alpha-actin. Immobilized proteins greatly enhanced adhering cell numbers, although for stimulation of SMC proliferation covalent immobilization was superior to physisorption.; *1H-NMR: 1H-nuclear magnetic resonance; GPC: gel permeation chromatography; DSC: differential scanning calorimetry; WAXS: wide-angle x-ray spectrometry; and DMA: dynamic-mechanical analysis.