Development of cardiac patches using medium chain length polyhydroxyalkanoates for cardiac tissue engineering

Medium chain length-PHAs (MCL-PHAs) have properties that make them exceptional for applications in cardiac tissue engineering. Cardiovascular diseases (CVD) are a major cause of death worldwide. Cardiac patches aim to facilitate the normal functioning of the heart muscle by providing repair and support to the infarcted tissue post myocardial infarction. In this project, two MCL-PHAs, poly(3-hydroxyoctanoate) (P(3HO) homopolymer and poly(3-hydroxynonanoate-co-3-hydroxyheptanoate) P(3HN-co-3HHP) were produced from Pseudomonas mendocina CH50 using sodium octanoate and sodium nonanoate respectively as the carbon source and the growth profiles were monitored for 48 h. The polymers were characterised to confirm the chemical structure of the polymers. Different types of scaffolds were fabricated like plain films, random fibres and aligned fibres, using different ratios of P(3HO) and P(3HN-co-3HHP) which were 100:0 (P(3HO)), 20:80 (P(3HO):P(3HN-co-3HHP), 50:50 (P(3HO):P(3HN-co-3HHP), 80:20 (P(3HO):P(3HN-co-3HHP) and 0:100 P(3HN-co-3HHP). The mechanical and thermal properties of the films were analysed along with the wettability of all the scaffolds. In vitro cytocompatibility studies were also conducted on all the different scaffolds (films, random and aligned fibres) by growing human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) on them. The cells were found to be viable and healthy with comparable beating rates and calcium transients to that measured on gelatin which was used as the positive control. The cell alignment quantification on the aligned fibres indicated around 50% of the cells were aligned in one direction. Porous 5 wt% 2D scaffolds and porous 20 wt% 3D structure were fabricated using P(3HO) and different concentrations of the porogen, sucrose and NaCl respectively, to obtain pores in the size range of 250-300 μm which exhibited decreased hydrophobicity compared to the neat scaffolds. In vitro cell culture with C2C12 exhibited higher cell proliferation rate on the porous P(3HO) structures as compared to the neat P(3HO) film. The P(3HO) and PANI (polyaniline) blend scaffolds were fabricated to introduce electrical conductivity and they were analysed for their material characteristics. The effect of the addition of PANI on cardiomyocyte proliferation was studied using neonatal ventricular rat myocardial cells (NVRM). A one step method involving the use of poly(ethylene oxide-stat-propylene oxide) with isocyanate end groups (NCO-sP(EO-stat-PO) was used for the incorporation of RGD, YIGSR peptides and the vascular endothelial growth factor (VEGF) on the surface of P(3HO)/P(3HN-co-3HHP) (80:20) electrospun fibres and enhanced cell viability was studied using NVRMs

Inside and Outside Money, Gains to Trade, and IS-LM

We build a one-period general equilibrium model with money. Equilibrium exists, and fiat money has positive value, as long as the ratio of outside money to inside money is less than the gains to trade available at autarky. We show that the nominal effects of government fiscal and monetary policy can be completely described by a diagram identical in form to the IS-LM curves introduced by Hicks to describe Keynes' general theory. IS-LM analysis is thus not incompatible with full market clearing, multiple commodities, and heterogeneous households. We show that as the government deficit approaches a finite threshold, hyperinflation sets in (prices converge to infinity and real trade collapses). If the government surplus is too large, the economy enters a liquidity trap in which nominal GNP sinks and monetary policy is ineffectual.

Insurance Contracts Designed by Competitive Pooling

We build a model of competitive pooling and show how insurance contracts emerge in equilibrium, designed by the invisible hand of perfect competition. When pools are exclusive, we obtain a unique separating equilibrium. When pools are not exclusive but seniority is recognized, we obtain a different unique equilibrium: the pivotal primary-secondary equilibrium. Here reliable and unreliable households take out a common primary insurance up to its maximum limit, and then unreliable households take out further secondary insurance.

Strategic Response with Perfect Information

Take a game in extensive form with perfect information. Start with an arbitrary choice of strategies by the players. Now let each player -- if he can -- deviate unilaterally to a strategy that will improve his payoff, on the assumption that the others stay put with their choices. This gives rise to a new revised choice of strategies. Iterate the process. We will show that the sequence of strategic choices thus generated becomes stationary, and (of course) constitutes a Nash Equilibrium (N.E.) of the game. This result is embarrassingly simple to prove but seems to us to merit being on record. It does somewhat more than re-establish the classical existence of an N.E. for such games. It shows that the N.E.'s are obtained under the simple dynamic of unilateral strategic improvements. Such improvements underlie the very notion of an N.E. (which is defined to occur when they cannot be made), and so it is natural to use them to set up an associated dynamic

Inefficiency of Nash Equilibria

The main theme of this paper is that Nash Equilibria of games with smooth payoff functions generally tend to be inefficient (in the Pareto sense)

Strategic Substitutes and Potential Games

We show that games of strategic substitutes (or complements) with aggregation are "pseudo-potential" games, and therefore possess Nash equilibria in pure strategies. Our notion of aggregation is quite general and enables us to take a unified view of several disparate models.

Default and Punishment in General Equilibrium

We extend the standard model of general equilibrium with incomplete markets to allow for default and punishment. The equilibrating variables include expected delivery rates, along with the usual prices of assets and commodities. By reinterpreting the variables, our model encompasses a broad range of moral hazard, adverse selection, and signalling phenomena (including the Akerlof lemons model and Rothschild--Stiglitz insurance model) in a general equilibrium framework. We impose a condition on the expected delivery rates for untraded assets that is similar to the trembling hand refinements used in game theory. Despite earlier claims about the nonexistence of equilibrium with adverse selection, we show that equilibrium always exists, even with exclusivity constraints on asset sales, and transactions-liquidity costs or information-evaluation costs for asset trade. We show that more lenient punishment which encourages default may be Pareto improving because it allows for better risk spreading. We also show that default opens the door to a theory of endogenous assets.