Fibrous 3D scaffolds for cardiac tissue engineering
DATE CREATED: Jan 7, 2009
ACTION PLAN
Once, fibers are obtained successfully, optimization Shilpa Tried various experiments to dissolve cured polymer in different organic solvents on Jan 8, but without
of fiber characters and more defined geometries instead success. It seems that prepolymer has to be used for electrospinning. Also tried different organic solvent for
of random woven mat other natural biomaterials. HFIP works only for pre-polymer. Finally, after lot of trials, could obtain
some fibers
Mechanical testing of the fibers Shilpa/Jason Very important to know if electrospun PGS pre-polymer has the desired mechanical properties. If not, have
to change the directions of the project.
PROBLEMS IDENTIFIED (PI) / OUTSIDE SKILL REQUIRED (OSR) / RESOLVED (R)
Project
Biodegradable 3 D tissue scaffolds of PGS for cardiac tissue engineering
A) Background:
The demand for organ transplantation has rapidly increased all over the world during the past decade due to the increased incidence of vital organ failure, the rising success and greater improvement in post-transplant outcome. However, the unavailability of adequate organs for transplantation to meet the existing demand has resulted in major organ shortage crises. To address this problem of organ shortage, the field of tissue engineering has emerged with the aim of generating artificial tissues that restore, maintain or enhance tissue function.
Driven by enormous clinical need, myocardial tissue engineering has become a prime focus of research within the field of tissue engineering to regenerate the injured heart, to overcome bad prognosis of patients with heart failure and to address the shortage of heart donors. Amongst the various cell types studied so far, pluripotent embryonic stem cells have the greatest potential to generate human cardiac tissue in vitro.
To engineer myocardial tissue which beats cyclically and throughout the life, biomaterial should be as soft and elastic as heart muscle. Polylactide, polyglycolide, polycaprolactone and their copolymers alone are not useful because of their thermoplasticity. In fact, no single biomaterial can provide all necessary properties required for a particular application, and hence, hybrid of natural and synthetic polymers should be designed to exploit their advantages. Although various research groups have demonstrated use of different biomaterials, very few groups have explored the combination of biomaterials. Recently, Fromstein, JD et al have shown that not only the biomaterial type but also its micro-architecture affects the cell behavior. This opens whole new prospects for tissue-engineered cardiac scaffolds.
Recently developed elastomer PGS has potential for soft tissue engineering, especially cardiac tissue engineering due to its mechanical properties and biocompatibility. Chemically, PGS looks like collagen because it forms a cross-linked three-dimensional network. Mechanically, PGS has a relatively low modulus and a large elongation similar to elastin, it can effectively transfer the appropriate micro-stresses to regenerating tissues. However, there are very few reports in the literature on the fabrication of PGS fibers due to the ilimitation on casting structures from this elastomer. Hence, we propose electrospinning PGS with other biomaterials like HA, collagen, alginate etc. in order to combine their individual advantages like biodegradability and mechanical properties to support the cardiac cells and generate 3D cardiac scaffolds in vitro.
B) Objective
Thus, the major objective of this project is to develop 3 D scaffolds of hybrid biocompatible, biodegradable materials for functional cardiac tissue.
C) GENERAL EXPERIMENTAL APPROACH
1. Electrospinning of PGS alone/in combination with natural biomaterials
2. Optimization of scaffold properties such as diameter/density/potosity
3. Evaluation of cell attachment, viability and proliferation onto the fibers by cell-based assays
4. Evaluation of functional ability of generated cardiac tissue by RT-PCR, Immunostaining, ultrastructural analysis
D) DESIGN PITFALLS AND ALTERNATIVES
E) POTENTIAL FIGURES FOR PAPER
Expected figures:
Table 1. Properties of the fibrous scaffolds (diameter/average pore size/thickness/mechanical properties)
Fig. 1. SEM of fibers
Fig. 2. Cell viability/proliferation of cells over period of days (5-9 days)
Fig. 3. Immunostaining for expression of cardiac-specific proteins
Fig. 4. Force of contarction of the cells (cardiac electric potential)
Fig. 5. SEM/confocal image analysis of cell-laden scaffolds
F) FUTURE DIRECTIONS