Polyhydroxyalkanoates (PHAs) are natural biopolymers produced by various microorganisms as a reserve of carbon and energy. PHA synthesis generally occurs during fermentation under nutrient limiting conditions with excess carbon. There are two main types of PHAs, short chain length PHAs (scl-PHAs) and medium chain length PHAs (mcl-PHAs). The mechanical and thermal properties of PHAs depend mainly on the number of carbons in the monomer unit and its molecular weight. PHAs are promising materials for biomedical applications because they are biodegradable, non-toxic and biocompatible. The large range of PHAs, along with their varying physical properties and high biocompatibility, make them highly attractive biomaterials for use in drug delivery. They can be used to produce tablets, micro-and nanoparticles as well as drug eluting scaffolds. A large range of different PHAs have been explored and the results obtained suggest that PHAs are excellent candidates for controlled and targeted drug delivery systems.
Cardiovascular diseases (CVD) constitute a major fraction of the current major global diseases and lead to about 30% of the deaths, i.e., 17.9 million deaths per year. CVD include coronary artery disease (CAD), myocardial infarction (MI), arrhythmias, heart failure, heart valve diseases, congenital heart disease, and cardiomyopathy. Cardiac Tissue Engineering (CTE) aims to address these conditions, the overall goal being the efficient regeneration of diseased cardiac tissue using an ideal combination of biomaterials and cells. Various cells have thus far been utilized in pre-clinical studies for CTE. These include adult stem cell populations (mesenchymal stem cells) and pluripotent stem cells (including autologous human induced pluripotent stem cells or allogenic human embryonic stem cells) with the latter undergoing differentiation to form functional cardiac cells. The ideal biomaterial for cardiac tissue engineering needs to have suitable material properties with the ability to support efficient attachment, growth, and differentiation of the cardiac cells, leading to the formation of functional cardiac tissue. In this review, we have focused on the use of biomaterials of natural origin for CTE. Natural biomaterials are generally known to be highly biocompatible and in addition are sustainable in nature. We have focused on those that have been widely explored in CTE and describe the original work and the current state of art. These include fibrinogen (in the context of Engineered Heart Tissue, EHT), collagen, alginate, silk, and Polyhydroxyalkanoates (PHAs). Amongst these, fibrinogen, collagen, alginate, and silk are isolated from natural sources whereas PHAs are produced via bacterial fermentation. Overall, these biomaterials have proven to be highly promising, displaying robust biocompatibility and, when combined with cells, an ability to enhance post-MI cardiac function in pre-clinical models. As such, CTE has great potential for future clinical solutions and hence can lead to a considerable reduction in mortality rates due to CVD.
SummaryThis study demonstrated the utilization of unprocessed biodiesel waste as a carbon feedstock for Pseudomonas mendocina CH50, for the production of PHAs. A PHA yield of 39.5% CDM was obtained using 5% (v/v) biodiesel waste substrate. Chemical analysis confirmed that the polymer produced was poly(3‐hydroxyhexanoate‐co‐3‐hydroxyoctanoate‐co‐3‐hydroxydecanoate‐co‐3‐hydroxydodecanoate) or P(3HHx‐3HO‐3HD‐3HDD). P(3HHx‐3HO‐3HD‐3HDD) was further characterized and evaluated for its use as a tissue engineering scaffold (TES). This study demonstrated that P(3HHx‐3HO‐3HD‐3HDD) was biocompatible with the C2C12 (myoblast) cell line. In fact, the % cell proliferation of C2C12 on the P(3HHx‐3HO‐3HD‐3HDD) scaffold was 72% higher than the standard tissue culture plastic confirming that this novel PHA was indeed a promising new material for soft tissue engineering.
Polyhydroxyalkanoates, a broad family of natural biodegradable and biocompatible polymers, have emerged as highly promising biomaterials both for bulk and biomedical applications. Here we describe an approach to tune the mechanical properties of stiff and brittle poly(3-hydroxybutyrate) and thereby to expand its potential biomedical applications. Plasticisation, a common practice in the plastic industry to modify polymer mechanical properties, has been used very cautiously for biomedical applications due to plasticiser toxicity and migration. We have developed a plasticiser for poly(3-hydroxybutyrate) based on a structurally related but softer and pliable medium chain length polyhydroxyalkanoate. Additives of oligomeric derivatives of this polymer improved ductility of poly(3-hydroxybutyrate), greatly widening the future applicability of this well-established biomaterial. In parallel, the binary polyhydroxyalkanoate materials also exhibited improved cell attachment and proliferation, a highly desirable outcome.
This study validated the utilization of triacylglycerides (TAGs) by Pseudomonas mendocina CH50, a wild type strain, resulting in the production of novel mcl-PHAs with unique physical properties. A PHA yield of 58% dcw was obtained using 20g/L of coconut oil. Chemical and structural characterisation confirmed that the mcl-PHA produced was a terpolymer comprising of three different repeating monomer units, 3hydroxyoctanoate, 3-hydroxydecanoate and 3-hydroxydodecanoate or P(3HO-3HD-3HDD). Bearing in mind the potential of P(3HO-3HD-3HDD) in biomedical research, especially in neural tissue engineering, in vitro biocompatibility studies were carried out using NG108-15 (neuronal) cells. Cell viability data confirmed that P(3HO-3HD-3HDD) supported the attachment and proliferation of NG108-15 and was therefore, confirmed to be biocompatible in nature and suitable for neural regeneration.
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