Polyhydroxyalkanoates (PHAs), natural polymers of bacterial origin as potential biomaterials in glomerular tissue engineering

Polyhydroxyalkanoates or PHAs, a family of natural polymers of bacterial origin produced via bacterial fermentation, have been utilised as a novel biomaterial potentially for glomerular tissue engineering. Generally, PHAs are biocompatible with a broad array of human cells and have been widely used in biomedical applications. This work tested PHA as a novel scaffold material for glomerular kidney cells; the human conditionally immortalised podocytes (CiHP) and human conditionally immortalised glomerular endothelial cells (CiGEnC).
All PHA samples were extensively characterised with respect to their physical, chemical, and thermal properties to gain in-depth information in the context of tissue engineering. The PHAs were processed to form a 2D structure using the solvent casting technique for a direct cytocompatibility assessment. 3D structures were produced by electrospinning and 3D printing using the Fused Deposition Modelling (FDM) method to further assess the cell's performance in a three-dimensional microenvironment. For the 2D substrate, medium chain-length PHA (mcl-PHA) produced by Pseudomonas mendocina CH50 with monomer composition up to C14 was initially used to test the cytocompatibility with respect to the glomerular cells.
The mcl-PHA demonstrated high biocompatibility comparable to that of the tissue culture plastics (TCP) as a standard control. Then, further cytocompatibility tests with different PHA samples were conducted; using a stiffer version of the PHA, poly(3-hydroxybutyrate), P(3HB), a type of short chain-length PHA (scl-PHA) produced by Bacteria PHAsT 1 and another type of mcl-PHA produced by Bacteria PHAsT 2, and the 1:1 blend of these scl- and mcl-PHAs. The glomerular cells exhibited excellent viability and growth, mainly on the mcl-PHA and the 1:1 PHA blend, better than on the known synthetic polymer, poly-ε-caprolactone, PCL, and the stiffer P(3HB). Meanwhile, 3D scaffolds were produced by electrospinning and 3D printing which further confirmed the excellent performance of the glomerular cells on these scaffolds. This demonstrated the guided growth of the glomerular cells with the design of the 3D structure of the fabricated PHA-based scaffolds. Furthermore, it was found that co-culturing the CiHP and CiGEnC resulted in superior viability as compared to monocultures, showing that cellular crosstalk is essential in sustaining cell performance.
In conclusion, the PHA, especially the mcl-PHA and the PHA blend, were found to be prospective biomaterials with the potential to substitute the readily available synthetic materials, as sustainable naturally derived materials with high biocompatibility, leading to further application in glomerular tissue engineering, and for in vitro 3D model development.