Polyhydroxyalkanoates (PHA) are microbial biopolyesters utilized as “green plastics”. Their production under controlled conditions resorts to bioreactors operated in different modes. Because PHA biosynthesis constitutes a multiphase process, both feeding strategy and bioreactor operation mode need smart adaptation. Traditional PHA production setups based on batch, repeated batch, fed-batch or cyclic fed-batch processes are often limited in productivity, or display insufficient controllability of polyester composition. For highly diluted substrate streams like it is the case for (agro)industrial waste streams, fed-batch enhanced by cell recycling were recently reported as a viable tool to increase volumetric productivity. As emerging trend, continuous fermentation processes in single-, two-, and multi-stage setups are reported, which bring the kinetics of both microbial growth and PHA accumulation into agreement with process engineering, and allow tailoring PHA´s molecular structure. Moreover, we currently witness an increasing number of CO2-based PHA production processes using cyanobacteria; these light-driven processes resort to photobioreactors similar to those used for microalgae cultivation, and can be operated both discontinuously and continuously. This development goes in parallel to the emerging use of methane and syngas as an abundantly available gaseous substrates, which also calls for bioreactor systems with optimized gas transfer. The review sheds light on the challenges of diverse PHA production processes in different bioreactor types and operational regimes using miscellaneous microbial production strains such as extremophilic Archaea, chemoheterotrophic eubacteria and phototrophic cyanobacteria. Particular emphasize is dedicated to the limitations and promises of different bioreactor-strain combinations, and to efforts devoted to upscaling these processes to industrially relevant scales.

Polyhydroxyalkanotes (PHA) are bio-based microbial biopolyesters with stiffness, elasticity, crystallinity and degradability tunable by the monomeric composition, bio-production strategy and post-synthetic processing; they display biological alternatives for diverse technomers of petrochemical origin. This, together with the fact that their monomeric and oligomeric in vivo degradation products do not exert any toxic or elsewhere negative effect to living cells or tissue of humans or animals, makes them highly stimulating for various applications in the medical field. The article provides an overview of PHA application in the therapeutic, surgical and tissue engineering area, and reviews strategies to produce PHA at purity levels high enough to be used in vivo. Tested applications of differently composed PHA and advanced follow-up products as carrier materials for controlled in vivo release of anti-cancer drugs or antibiotics, as scaffolds for tissue engineering, as guidance conduits for nerve repair or as enhanced sutures, implants or meshes are discussed from both a biotechnological and a material-scientific perspective. Particular attention is devoted to the adaptation of traditional polymer processing techniques for production of medicine-related devices based on PHA, such as melt-spinning, melt extrusion, or solvent evaporation, and to emerging processing techniques like 3D-printing, computer-aided wet-spinning, laser perforation, or electrospinning.

Global pollution from fossil plastics is one of the top environmental threats of our times. The end-of-life scenarios of fossil plastic, including recycling, incineration and disposal result in mi-croplastic formation, elevated atmospheric CO2 levels, and littering of terrestrial and aquatic environments by plastic waste. Currently thought-out regulations centered around banning plastics production and use and only recycling on a regional, national and global level are impeding efforts to rapidly replace fossil plastics through the use of natural alternatives. In particular, this review demonstrates how mi-crobial polyhydroxyalkanoates (PHA), a class of intrinsically natural polymers, can easily remedy for the fossil and persistent plastic dilemma. PHA are bio-based, bio-synthesized, bio-compatible, bio-degradable, and home- and industrially compostable. Therefore, they are one of the perfect replacements for our fossil plastics pollution dilemma, providing us with the benefits of fossil plastics and meeting all requirements of a truly circular economy. PHA biopolyesters are natural and green materials in all aspects of their life cycle. The review elaborates in detail how PHA’s production, consumption, and end-of-life profile are perfectly embedded in the current topical 12 Principles of Green Chemistry, which constitute the basis for sustainable product manufacturing. It is shown that it is time for a paradigm shift in plastics manufacturing, use and disposal. Hu-mankind needs alternatives to fossil plastics, which, as recalcitrant xenobiotics, contribute to the increasing deterioration of our planet. Natural PHA biopolyesters represent that paradigm shift!