Polyhydroxyalkanoates (PHA) are bio-based microbial biopolyesters; their stiffness, elasticity, crystallinity and degradability are tunable by the monomeric composition, selection of microbial ...production strain, substrates, process parameters during production, and post-synthetic processing; they display biological alternatives for diverse technomers of petrochemical origin. This, together with the fact that their monomeric and oligomeric
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. This 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
. Tested applications of differently composed PHA and advanced follow-up products as carrier materials for controlled
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. The article also describes the use of traditional processing techniques for production of PHA-based medical devices, such as melt-spinning, melt extrusion, or solvent evaporation, and emerging processing techniques like 3D-printing, computer-aided wet-spinning, laser perforation, and electrospinning.
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 is the case of (agro) industrial waste streams, fed-batch enhanced by cell recycling has recently been reported as a viable tool to increase volumetric productivity. As an 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 is parallel to the emerging use of methane and syngas as 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 emphasis is dedicated to the limitations and promises of different bioreactor–strain combinations and to efforts devoted to upscaling these processes to industrially relevant scales.
Downstream processing for recovery of microbial polyhydroxyalkanoate (PHA) biopolyesters from biomass constitutes an integral part of the entire PHA production chain; beside the feedstocks used for ...cultivation of PHA-production strains, this process is currently considered the major cost factor for PHA production.
Besides economic aspects, PHA recovery techniques need to be sustainable by avoiding excessive use of (often precarious!) solvents, other hazardous chemicals, non-recyclable compounds, and energy. Moreover, the applied PHA recovery method is decisive for the molecular mass and purity of the obtained product, and the achievable recovery yield. In addition to the applied method, also the PHA content in biomass is decisive for the feasibility of a selected technique. Further, not all investigated recovery techniques are applicable for all types of PHA (crystalline versus amorphous PHA) and all PHA-producing microorganisms (robust versus fragile cell structures).
The present review shines a light on benefits and shortcomings of established solvent-based, chemical, enzymatic, and mechanical methods for PHA recovery. Focus is dedicated on innovative, novel recovery strategies, encompassing the use of “green” solvents, application of classical “PHA anti-solvents” under pressurized conditions, ionic liquids, supercritical solvents, hypotonic cell disintegration for release of PHA granules, switchable anionic surfactants, and even digestion of non-PHA biomass by animals.
The different established and novel techniques are compared in terms of PHA recovery yield, product purity, impact on PHA molar mass, scalability to industrial plants, and demand for chemicals, energy, and time.
Haloarchaea, the extremely halophilic branch of the Archaea domain, encompass a steadily increasing number of genera and associated species which accumulate polyhydroxyalkanoate biopolyesters in ...their cytoplasm. Such ancient organisms, which thrive in highly challenging, often hostile habitats characterized by salinities between 100 and 300 g/L NaCl, have the potential to outperform established polyhydroxyalkanoate production strains. As detailed in the review, this optimization presents due to multifarious reasons, including: cultivation setups at extreme salinities can be performed at minimized sterility precautions by excluding the growth of microbial contaminants; the high inner-osmotic pressure in haloarchaea cells facilitates the recovery of intracellular biopolyester granules by cell disintegration in hypo-osmotic media; many haloarchaea utilize carbon-rich waste streams as main substrates for growth and polyhydroxyalkanoate biosynthesis, which allows coupling polyhydroxyalkanoate production with bio-economic waste management; finally, in many cases, haloarchaea are reported to produce copolyesters from structurally unrelated inexpensive substrates, and polyhydroxyalkanoate biosynthesis often occurs in parallel to the production of additional marketable bio-products like pigments or polysaccharides. This review summarizes the current knowledge about polyhydroxyalkanoate production by diverse haloarchaea; this covers the detection of new haloarchaea producing polyhydroxyalkanoates, understanding the genetic and enzymatic particularities of such organisms, kinetic aspects, material characterization, upscaling and techno-economic and life cycle assessment.
The benefit of biodegradable “green plastics” over established synthetic plastics from petro-chemistry, namely their complete degradation and safe disposal, makes them attractive for use in various ...fields, including agriculture, food packaging, and the biomedical and pharmaceutical sector. In this context, microbial polyhydroxyalkanoates (PHA) are auspicious biodegradable plastic-like polyesters that are considered to exert less environmental burden if compared to polymers derived from fossil resources.
The question of environmental and economic superiority of bio-plastics has inspired innumerable scientists during the last decades. As a matter of fact, bio-plastics like PHA have inherent economic drawbacks compared to plastics from fossil resources; they typically have higher raw material costs, and the processes are of lower productivity and are often still in the infancy of their technical development. This explains that it is no trivial task to get down the advantage of fossil-based competitors on the plastic market. Therefore, the market success of biopolymers like PHA requires R&D progress at all stages of the production chain in order to compensate for this disadvantage, especially as long as fossil resources are still available at an ecologically unjustifiable price as it does today.
Ecological performance is, although a logical argument for biopolymers in general, not sufficient to make industry and the society switch from established plastics to bio-alternatives. On the one hand, the review highlights that there’s indeed an urgent necessity to switch to such alternatives; on the other hand, it demonstrates the individual stages of the production chain, which need to be addressed to make PHA competitive in economic, environmental, ethical, and performance-related terms. In addition, it is demonstrated how new, smart PHA-based materials can be designed, which meet the customer’s expectations when applied, e.g., in the biomedical or food packaging sector.
The ever-increasing use of plastics, their fossil origin, and especially their persistence in nature have started a wave of new innovations in materials that are renewable, offer the functionalities ...of plastics, and are biodegradable. One such class of biopolymers, polyhydroxyalkanoates (PHAs), are biosynthesized by numerous microorganisms through the conversion of carbon-rich renewable resources. PHA homo- and heteropolyesters are intracellular products of secondary microbial metabolism. When isolated from microbial biomass, PHA biopolymers mimic the functionalities of many of the top-selling plastics of petrochemical origin, but biodegrade in soil, freshwater, and marine environments, and are both industrial- and home-compostable. Only a handful of PHA biopolymers have been studied in-depth, and five of these reliably match the desired material properties of established fossil plastics. Realizing the positive attributes of PHA biopolymers, several established chemical companies and numerous start-ups, brand owners, and converters have begun to produce and use PHA in a variety of industrial and consumer applications, in what can be described as the emergence of the "PHA industry". While this positive industrial and commercial relevance of PHA can hardly be described as the first wave in its commercial development, it is nonetheless a very serious one with over 25 companies and start-ups and 30+ brand owners announcing partnerships in PHA production and use. The combined product portfolio of the producing companies is restricted to five types of PHA, namely poly(3-hydroxybutyrate), poly(4-hydroxybutyrate), poly(3-hydroxybutyrate-
-3-hydroxyvalerate), poly(3-hydroxybutyrate-
-4-hydroxybutyrate), and poly(3-hydroxybutyrate-
-3-hydroxyhexanoate), even though PHAs as a class of polymers offer the potential to generate almost limitless combinations of polymers beneficial to humankind. To date, by varying the co-monomer type and content in these PHA biopolymers, their properties emulate those of the seven top-selling fossil plastics, representing 230 million t of annual plastics production. Capacity expansions of 1.5 million t over the next 5 years have been announced. Policymakers worldwide have taken notice and are encouraging industry to adopt biodegradable and compostable material solutions. This wave of commercialization of PHAs in single-use and in durable applications holds the potential to make the decisive quantum leap in reducing plastic pollution, the depletion of fossil resources, and the emission of greenhouse gases and thus fighting climate change. This review presents setbacks and success stories of the past 40 years and the current commercialization wave of PHA biopolymers, their properties, and their fields of application.
This editorial paper provides a synopsis of the contributions to the
special issue "Advances in Polyhydroxyalkanoate (PHA) Production". It illustrates the embedding of the issue's individual research ...articles in the current global research and development landscape related to polyhydroxyalkanoates (PHA). The article shows how these articles are interrelated to each other, reflecting the entire PHA process chain including strain selection, metabolic and genetic considerations, feedstock evaluation, fermentation regimes, process engineering, and polymer processing towards high-value marketable products.
Steadily increasing R&D activities in the field of microbial polyhydroxyalkanoate (PHA) biopolyesters are committed to growing global threats from climate change, aggravating plastic pollution, and ...the shortage of fossil resources. These prevailing issues paved the way to launch the third Special Issue of Bioengineering dedicated to future-oriented biomaterials, characterized by their versatile plastic-like properties. Fifteen individual contributions to the Special Issue, written by renowned groups of researchers from all over the world, perfectly mirror the current research directions in the PHA sector: inexpensive feedstock like carbon-rich waste from agriculture, mitigation of CO2 for PHA biosynthesis by cyanobacteria or wild type and engineered “knallgas” bacteria, powerful extremophilic PHA production strains, novel tools for rapid in situ determination of PHA in photobioreactors, modelling of the dynamics of PHA production by mixed microbial cultures from inexpensive raw materials, enhanced bioreactor design for high-throughput PHA production by sophisticated cell retention systems, sustainable and efficient PHA recovery from biomass assisted by supercritical water, enhanced processing of PHA by application of novel antioxidant additives, and the development of compatible biopolymer blends. Moreover, elastomeric medium chain length PHA (mcl-PHA) are covered in-depth, inter alia, by introduction of a novel class of bioactive mcl-PHA-based networks, in addition to the first presentation of the new rubber-like polythioester poly(3-mercapto-2-methylpropionate). Finally, the present Special Issue is concluded by a critical essay on past, ongoing, and announced global endeavors for PHA commercialization.
: Current threats connected to the ongoing depletion of fossil resources and elevated levels of greenhouse gases accelerating climate change and global warming provoke a renaissance of ...biotechnological production of various organic bulk chemicals, which, particularly during the second half of the 20th century, were almost exclusively produced from fossil resources via chemosynthetic processes.
: Besides the manufacture of bioethanol, a product obtained by microbial fermentation, biogenic production of solvents and energy carriers like acetone, isopropanol, 2,3-butanediol, or 1-butanol, hence, processes known since the beginning of the last century, experiences now a substantial revival.
: The review illustrates how to produce these products by resorting to fossil raw materials instead of petrochemical production processes, and how this can be accomplished by the cultivation of anaerobic organisms, namely facultatively anaerobic yeasts and bacteria (production of ethanol or 2,3-butanediol), and strictly anaerobic Clostridia (1-butanol, acetone, or isopropanol) on renewable resources. Moreover, novel methods for producing biodiesel-like methyl-esters of aerobically produced bacterial polyhydroxyalkanoate biopolyester building blocks combine the synthesis of microbial biopolyesters from wastewater with the progress of innovative renewable energy carriers. The biochemical background, the current state of research and development, and the status of industrialization of these processes are reviewed.
: Challenges to make these bioprocesses, based on inexpensive renewable resources, competitive with or even superior to petrochemical production routes in terms of sustainability, scalability, and economic feasibility still exist: however, they can be overcome by the concerted action of various scientific disciplines.
During the two years that have passed since the first volume of "Advances in Polyhydroxyalkanoate (PHA) production" was published, the progress in PHA-related research was indeed tremendous, calling ...for the next, highly bioprocess- and bioengineering-oriented volume. This editorial paper summarizes and puts into context the contributions to this second volume of the
Special Issue; it covers highly topical fields of PHA-related R&D activities, covering, beside the pronounced bioengineering-related articles, the fields of the microbiology of underexplored, but probably emerging, PHA production strains from the groups of
, cyanobacteria, methanotrophs, and from the extremophilic domain of haloarchaea. Moreover, novel second-generation lignocellulose feedstocks for PHA production from agriculture to be used in biorefinery concepts, new approaches for fine-tuning the composition of PHA co- and terpolyesters, process simulation for PHA production from methane-rich natural gas, the challenges associated with rheology-governed oxygen transfer in high cell density cultivations, rapid spectroscopic in-line analytics for process monitoring, and the biomedical application of PHA biopolyesters after appropriate advanced processing are the subjects of the presented studies.
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