A biologically safe, sustainable, plant-based plastic and its novel application for a greener laboratory
Any scientist who has worked in a laboratory would be aware of the mountain of countless single-use, non-renewable plastic pipette tips, serological syringes, tubes, dishes and flasks that are disposed of during cell culture. Despite their convenience and sterility, clinical waste and its safe disposal through incineration continues to pollute and harm the environment – the National Health Service in the UK produces nearly 156,000 tons of clinical waste for incineration per year (1).
The heavy reliance on single-use petroleum-based plastic lab consumables (polystyrene, polypropylene etc.) in scientific research, predominantly biomedical research and the biopharmaceutical industry, is a major environmental problem that hinders progress towards a sustainable society. While biomedical research is striving for a world of healthy people, the current trends are not contributing towards a healthy planet. Petroleum-based plastics drive climate change by contributing towards:
Immense carbon emissions – According to ARUP’s 2019 report, the climate footprint of the healthcare industry (including the biotech and pharma industries) was two gigaton of CO₂ equivalent, representing 4.4% of total global emissions (2). 71% of the sector’s emissions were derived from the healthcare supply chain, including the manufacturing of petroleum-based goods and their use (2). Furthermore, carbon emissions produced through high temperature incineration of the single-use plastic clinical waste and the running of these facilities contributes to pollution.
Depletion of fossil fuel oil reserves – Conventional synthetic polymers are produced using oil and gas reserves, and during the production process, there is large reliance on non-renewable energy use that draw on these oil reserves that take years to regenerate. The detrimental environmental impact of the oil and gas industry as well as the rise in oil prices drives climate change (3).
Society is becoming increasingly concerned about carbon emissions across all sectors. With governments implementing net-zero carbon targets and the Paris Agreement pushing for rapid climate action across all sectors, it’s time that the biomedical and biopharmaceutical sectors re-think their practices to move towards a more sustainable future (4). Particularly in cell culture, options for growing and expanding adherent cells are either stacks of plastic T-flasks or cell factories, or hefty bioreactors. Transforming plastic usage in this sector and making labs greener will greatly improve the sustainability of laboratory practices and reduce environmental pollution.
What if there's an alternative plastic for cell culture, that generates significantly less carbon emissions during production, is produced from renewable sources, and is biocompatible?
Pleased to meet you, PLA – the sustainable bioplastic solution
Introducing polylactic acid, or PLA – a renewable, biodegradable, plant-based polymer produced using crops such as corn starch or sugarcane (5). PLA is synthesized through the fermentation of glucose produced from organic plants (5). The resulting lactic acid is transformed into lactide, which, after a type of polymerization called ring-opening polymerization, produces the polylactic acid polymer (5). Since PLA production originates from primary feedstock, this ensures high yield of the PLA product. Furthermore, the numerous purification processes after lactic acid extraction ensures high-quality consistency and limited batch variability throughout production batches of PLA (6). The bioplastic, polylactic acid (PLA) plastic, has comparable mechanical properties to PET plastic and polypropylene, presenting as a practical, greener alternative to existing laboratory plastics (3).
The environmentally friendly manufacturing of PLA is a major advantage. Its use within the laboratory will greatly contribute towards reducing its carbon footprint.
Reduced carbon emissions – crops grown for PLA synthesis remove CO₂ from the atmosphere, therefore greatly reducing the CO₂ emissions during the PLA production process compared to petroleum-based plastics (3).
Energy and Water Saving – 25-55% less energy is consumed when producing PLA compared to petroleum-based plastics, further reducing the reliance on non-renewable energy sources for production and the subsequent carbon footprint (7). Some versions of PLA which use wind power during the production process can reduce fossil fuel use by 90% (5). In addition to reduced energy consumption, the total amount of water required for PLA production can be over 85% lower than water usage for production of plastics such as Nylon (5).
Produced using renewable resources – rather than drawing on oil or gas reserves for production, PLA is synthesized from plant products, greatly contrasting to petroleum-based plastics.
Sustainable end-of life options – current plastic polymer disposal involves incineration, landfill and mechanical recycling (3). PLA can utilize these disposal methods and the environmental benefits would still hold for the above-mentioned reasons. In saying this, PLA is also biodegradable through composting by bacterial and fungal degradation which allows for carbon recycling (3).
As well as its existing applications for textiles and packaging, further properties of PLA including the processability to tailor properties, and its biodegradability and biocompatibility in the body has led to PLA playing an increasingly important role as a safe bioplastic for medical applications (3).
Why biomedical engineers love PLA…
The processability is a major advantage of PLA. The ability to easily tailor mechanical, microstructural, chemical and degradation properties in addition to its ability to be blended and copolymerized with other polymer components has allowed PLA to be repurposed for a variety of different applications (8, 9). Its thermal processability compared to other biopolymers gives rise to numerous options for processing including injection molding, film extrusion and blow molding to name a few, further diversifying the applications of PLA for medical applications (9).
The biodegradability of PLA in the body and the biological compatibility of the degraded products has allowed the use of PLA in a range of surgical and medical applications. When in the body, PLA is degraded in a two-step process: 1) Hydrolysis (breakdown by water) decreases the molecular weight of PLA and produces water-soluble oligomers which are then 2) enzymatically broken down into lactic acid which is metabolized into CO₂ and H₂O (10, 11). While the degradation rate is influenced by the modifiable characteristics of PLA (e.g., molecular composition, crystallinity, molecular weight) and the hydrolysis environment (e.g., pH, temperature), PLA has been found to fully biodegrade between 30 weeks to 3 years (10, 11). PLA is biologically non-toxic and biocompatible and has been classified as Generally Recognized as Safe (GRAS) by the FDA for biological fluids which is a further factor supporting its biological safety (12).
These advantages have led to the increase in the use of PLA across medical applications including drug carriers, surgical sutures, stents, biodegradable screws, implants and scaffolds for tissue engineering, the latter being highly relevant for PLA’s potential in the laboratory for cell culture (3, 9).
PLA scaffolds to grow bone cells?!
Tissue engineering aims to regenerate, replace, sustain or improve damaged tissue structure or function using scaffolds, bioactive molecules and or cells (13, 14). PLA has been used as a scaffold for tissue engineering. The biocompatibility of the bioplastic ensures cell growth, and gradual degradation of the PLA scaffold leaves the newly grown tissue (14). PLA has been 3D printed to create porous scaffolds for culturing different cell types used for cell-based gene therapies for cardiovascular diseases, muscle tissues and bone cartilage regeneration (12). Specifically, PLA has been used for bone scaffolds for individuals with bone defects caused by trauma, osteoarthritis, osteoporosis, cancer or congenital malformations by combining autologous cells with the biomaterial (15). The ability to treat the PLA surface with osteoconductive treatments such as hydroxyapatite to promote bone cell growth has increased the value of the bioplastic as a novel scaffold material for bone tissue engineering (12). Cells such as Bone Marrow Mesenchymal Stem Cells and Osteosarcoma cells tested on the PLA scaffold showed cell viability and non-toxicity, promoting the use of PLA as a safe material for bone scaffolds in tissue engineering (16, 17).
While the use of PLA for medical applications is well established, PLA is yet to be introduced for cell culture applications within the laboratory. Green Elephant Biotech sees PLA as a solution to the environmental problem in the biotech and pharma industries, and recognizes the immense value of PLA as a bioplastic from a sustainability and biological perspective. The start-up is pioneering the use of PLA and its novel application as a bioplastic to produce sustainable lab consumables for cell culture, therefore providing a green solution for laboratories. To support the use of PLA for HEK-293 cell culture, Green Elephant tested the attachment and expansion of HEK-293 cells on the PLA surface - its success can be seen in the Application Note here.
The future of PLA for cell culture
The use of the PLA bioplastic for tissue engineering and its biocompatibility provides evidence supporting its biological safety, and its novel application for cell culture in the laboratory. The thermoplastic can be molded while retaining its properties, and can be easily sterilized, therefore posing as an alternative material for non-renewable plastics. The consistency of PLA quality and limited batch variability makes it a reliable material for use. The ease of changing the PLA surface functionality for cell culture through treatment to optimize for cell attachment and growth proves advantageous for applications within cell culture. Emerging research is proposing the potential to use PLA for organ-on-a-chip and microfluidics cell culture applications due to PLA’s surface properties, renewable origins, compatibility for high volume production and biocompatibility (18). More importantly, introducing PLA for cell culture within the lab will transform the environmental footprint of the industry to help laboratories become greener and progress towards a sustainable future for both the people and the planet.
PLA may still be in its early days when it comes to its use as a material for laboratory cell culture, but with the sustainability advantages and uses for medical applications being well-established, all we need is a willingness to change the industry, to make the sustainable future we dream of, a reality.
References
(1) NHS England. (2023, March 7). NHS clinical waste strategy. Retrieved from https://www.england.nhs.uk/long-read/nhs-clinical-waste-strategy/ (2) Health Care Without Harm. How the Health Sector Contributes to the Global Climate Crisis and Opportunities for Action. [Internet]. 2019 [cited 2023 Jun 2]. Available from: https://noharm-global.org/sites/default/files/documents-files/5961/HealthCaresClimateFootprint_090619.pdf (3) Rajeshkumar G, Arvindh Seshadri S, Devnani GL, Sanjay MR, Siengchin S, Prakash Maran J, et al. Environment friendly, renewable and sustainable poly lactic acid (PLA) based natural fiber reinforced composites – A comprehensive review. Journal of Cleaner Production. 2021 Aug;310:127483. (4) United Nations. Net Zero Coalition. 2021. https://www.un.org/en/climatechange/net-zero-coalition. (5) NatureWorks LLC. Biodegradable and sustainable fibers. Technical Bulletin. 2005. Available from: https://www.natureworksllc.com/~/media/Technical_Resources/Ingeo_Technical_Bulletins/TechnicalBulletin_BiodegradableSustainableFibers_Chap6_2005_pdf.pdf [Accessed May 03, 2023]. (6) European Bioplastics. Feedstock. [Internet]. 2023 Mar 28 [cited 2023 May 24]. Available from: https://www.european-bioplastics.org/bioplastics/feedstock/ (7) Vink ETH, Rábago KR, Glassner DA, Gruber PR. Applications of life cycle assessment to NatureWorksTM polylactide (PLA) production. Polymer Degradation and Stability. 2003 Jan;80(3):403–19. (8) Gupta B, Revagade N, Hilborn J. Poly(lactic acid) fiber: An overview. Progress in Polymer Science. 2007 Apr;32(4):455–82. (9) Farah S, Anderson DG, Langer R. Physical and mechanical properties of PLA, and their functions in widespread applications — A comprehensive review. Advanced Drug Delivery Reviews [Internet]. 2016 Dec;107:367–92. Available from: https://core.ac.uk/download/pdf/143478508.pdf (10) da Silva D, Kaduri M, Poley M, Adir O, Krinsky N, Shainsky-Roitman J, et al. Biocompatibility, biodegradation and excretion of polylactic acid (PLA) in medical implants and theranostic systems. Chemical Engineering Journal. 2018 May;340:9–14. (11) Feng P, Jia J, Liu M, Peng S, Zhao Z, Shuai C. Degradation mechanisms and acceleration strategies of poly (lactic acid) scaffold for bone regeneration. Materials & Design. 2021 Nov;210:110066. (12) DeStefano V, Khan S, Tabada A. Applications of PLA in modern medicine. Engineered Regeneration. 2020;1(1):76–87. (13) Santoro M, Shah SR, Walker JL, Mikos AG. Poly(lactic acid) nanofibrous scaffolds for tissue engineering. Advanced Drug Delivery Reviews. 2016 Dec;107:206–12. (14) Gregor A, Filová E, Novák M, Kronek J, Chlup H, Buzgo M, et al. Designing of PLA scaffolds for bone tissue replacement fabricated by ordinary commercial 3D printer. Journal of Biological Engineering. 2017 Oct 16;11(1). (15) Liu S, Qin S, He M, Zhou D, Qin Q, Wang H. Current applications of poly(lactic acid) composites in tissue engineering and drug delivery. Composites Part B: Engineering. 2020 Oct;199:108238. (16) Grémare A, Guduric V, Bareille R, Heroguez V, Latour S, L’heureux N, et al. Characterization of printed PLA scaffolds for bone tissue engineering. Journal of Biomedical Materials Research Part A. 2017 Nov 20;106(4):887–94. (17) Velioglu ZB, Pulat D, Demirbakan B, Ozcan B, Bayrak E, Erisken C. 3D-printed poly(lactic acid) scaffolds for trabecular bone repair and regeneration: scaffold and native bone characterization. Connective Tissue Research. 2018 Jul 30;60(3):274–82. (18) Ongaro AE, Di Giuseppe D, Kermanizadeh A, Miguelez Crespo A, Mencattini A, Ghibelli L, et al. Polylactic is a Sustainable, Low Absorption, Low Autofluorescence Alternative to Other Plastics for Microfluidic and Organ-on-Chip Applications. Analytical Chemistry. 2020 Apr 1;92(9):6693–701.