Biomedical Applications of Bacteria-Derived Polymers

Abstract

Plastics have found widespread use in the fields of cosmetic, engineering, and medical sciences due to their wide-ranging mechanical and physical properties, as well as suitability in biomedical applications. However, in the light of the environmental cost of further upscaling current methods of synthesizing many plastics, work has recently focused on the manufacture of these polymers using biological methods (often bacterial fermentation), which brings with them the advantages of both low temperature synthesis and a reduced reliance on potentially toxic and non-eco-friendly compounds. This can be seen as a boon in the biomaterials industry, where there is a need for highly bespoke, biocompatible, processable polymers with unique biological properties, for the regeneration and replacement of a large number of tissue types, following disease. However, barriers still remain to the mass-production of some of these polymers, necessitating new research. This review attempts a critical analysis of the contemporary literature concerning the use of a number of bacteria-derived polymers in the context of biomedical applications, including the biosynthetic pathways and organisms involved, as well as the challenges surrounding their mass production. This review will also consider the unique properties of these bacteria-derived polymers, contributing to bioactivity, including antibacterial properties, oxygen permittivity, and properties pertaining to cell adhesion, proliferation, and differentiation. Finally, the review will select notable examples in literature to indicate future directions, should the aforementioned barriers be addressed, as well as improvements to current bacterial fermentation methods that could help to address these barriers.

Keywords: bacteria; biodegradable polymers; biomaterial; biopolymer; biosynthesis; drug delivery; hydrogel; polymer science; regenerative medicine; tissue engineering.

Figure 1

Molecular structure of dextran.

Figure 2

(a) The structure of glycogen, (b) biosynthetic pathway, and (c) regulatory pathway for glycogen accumulation in bacterial systems. Used with permission from Cifuente et al. [68]. © 2021 The Author(s). Published by Elsevier B.V.

Figure 3

The process of using the flexible crosslinking nature of glycogen to produce a nanohydroxyapatite/collagen scaffold for the differentiation of bone and cartilage tissue. Reprinted with permission from Zhang et al. [83]. Copyright © American Chemical Society.

Figure 4

Structure of alginate (a) monomer, (b) chain conformation, and (c) distribution [120].

Figure 5

Schematic representation of biosynthesis of alginate in P. aeruginosa. Modified with permission from Schmid et al. [121].

Figure 6

The popular modifications and potential biomedical applications of hyaluronic acid. Used with permission from Fallacara et al. [142]. Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Figure 7

The backbone of the hyaluronan molecule, with the main constituents of d-glucuronic acid (left) connected via ester linkage to N-acetyl glucosamine (right). Reused with permission from Ward et al. [145]. Copyright © 2021 Elsevier Science B.V. All rights reserved.

Figure 8

The chemical structure of n repeating units in gellan gum. Reused with permission from Zhang et al. [190]. Copyright © 2021 Elsevier. All rights reserved.

Figure 9

Chemical structure of xanthan gum, (a) chair, and (b) Haworth projection [209].

Figure 10

Structure of β-(1,3)-glucans, curdlan.

Figure 11

The general chemical structure of PHAs.

Figure 12

PHA biosynthetic pathways producing scl-PHAs and mcl-PHAs [251].

Figure 13

(a) PDLA, (b) PLLA, and (c) PDLLA, where n and m are integers of the repetition units.

Figure 13

(a) PDLA, (b) PLLA, and (c) PDLLA, where n and m are integers of the repetition units.

Figure 14

A schematic presentation of the PLA production pathway by recombinant E. coli. Adapted with permission from a report by Jung and Lee [304]. Copyright © 2021, Elsevier.

Figure 15

The polymeric structure of ε-poly-l-lysine, where n is integer of the repetition units.

Figure 16

(a) Diagram of mussel attachment, polylysine is contained with the plaque; (b) the primary amino acid sequence of mfp-5; (c) Conjugation of dopamine onto the mfp-5 mimetic polymer; (d) Horseradish Peroxidase (HRP) crosslinking of the polymer to form a hydrogel; and (e) application of polymer onto a mouse wound model. Used with permission from a report by Wang et al. [333] © 2021 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 17

Molecular structure of γ-PGA (note the n number and similarity to nylon).

Figure 18

Basic molecular structure of polyphosphate, where n is the number of repeating units.