3D printing, also known as additive manufacturing, is revolutionizing the way we create solid objects from digital files. It is now accessible to the masses and being used across a variety of fields, including biomedicine. With the ability to manufacture pharmaceutical products, prosthetic ears, and even artificial organs, the potential of 3D printing in biomedicine is limitless. In this in-depth report, we analyze the latest trends and exciting innovations in 3D printing technology and materials in biomedicine, including tissue and organ fabrication, implants and prosthetics, and more. 

Trends and innovations in biomedical 3D printing

We are in the middle of a 3D printing revolution. Once available to only major research universities and Fortune 500 companies, 3D printing technology has become increasingly mainstream, with 2.2 million units of 3D printers shipped in 2021 . This number is set to rise to 21.5 million by 2030, bringing this rapid prototyping technology to the masses.

Seemingly every major industry, from aerospace to construction, leverages 3D printing technology for rapid and cost-effective manufacturing. Of all industries embracing the power of 3D printing, biomedical engineering holds the greatest potential for its applications. In this article, we will explore the rise of 3D printing in healthcare and medicine.

How it all began — the history of 3D printing

When Japanese inventor Hideo Kodama filed the first patent for a “ rapid prototyping device ” in 1981, the concept seemed doomed from the start, as Dr. Kodama quickly abandoned financing the patent the following year. Yet the idea provided the catalyst for further innovations. In 1984, Charles Hall filed a patent for a stereolithography system (SLA), a 3D printing technology widely used to this day. The first commercially available 3D printer followed in 1988, based on the groundbreaking SLA technology.

Other key 3D printing technologies soon followed. By the late 1980s, patents had been filed for two further types of additive manufacturing devices: fused deposition modeling (FDM) and selective laser sintering (SLS). FDM works by a technique called extrusion, where a nozzle deposits the heated material layer-by-layer to build up the 3D product. SLS works somewhat differently; the process involves spreading layers of powder-based material over the build platform, followed by the rapid solidification (or ‘sintering’) for each layer of the 3D-printed product. Subsequently, “jetting” (a modified version of 2D inkjet printing technology) and vat photopolymerization soon followed.

These technologies were originally limited to patent holders. However, with the expiry of those patents and the invention of the RepRap open-source concept, new companies can now make a name for themselves in this exciting field. Many of the largest breakthroughs have been in the field of biomedicine, including the development of the first 3D-printed organ for transplant surgery — a bladder.

Today, 3D printing for biomedical applications is booming. The global market size of biomedical 3D printing was estimated at $1.45 billion in 2021 and is expected to rise to approximately $6.21 billion by 2030. To uncover key trends in biomedical 3D printing, we analyzed data from the CAS Content Collection™, the largest human-curated collection of published scientific knowledge.

Technologies and materials in 3D printing

3D printing falls into four broad categories — powder bed fusion, jetting, extrusion, and photopolymerization. Due to the diverse range of applications, there is no one ‘one-size-fits-all’ 3D printing technology. Extrusion-based technologies such as FDM, however, remain the most popular types of biomedical 3D printing (Figure 1).

From plastics and metals to natural substances, a vast array of materials can be utilized in biomedical 3D printing. Synthetic polymers such as polycaprolactone and poly(lactic acid) rank among the most commonly used 3D printing materials (Figure 2), owing to their applications in microfluidics and medical implants . The most widely used inorganic substance is hydroxylapatite, which is used as a dental material and a filler for bone repair. A variety of natural polymers such as alginate and hyaluronic acid are gaining popularity in bioprinting.

The rise of biomedical 3D printing

Annual trends of journal and patent publications for biomedical 3D printing applications indicate that innovation in this area is booming, though the number of journal publications was dramatically higher (approximately 15,000) than patent publications (approximately 5,700) (Figure 3). This trend may reflect the increased commercialization of the technology in recent years.

Approximately 90 countries have published papers on the biomedical 3D printing applications, hinting at a widespread interest in this technology. Of these nations, the U.S. and China led the way, having the most publications for both journal and patent publications (Figures 4 and 5).

When we break down the biomedical 3D printing trend in patent assignees, we can see that most patents have been assigned to 3M, a US-based company. Other active countries in publishing patents include Korea, Lichtenstein, France, and China (Figure 6).

Innovative applications of biomedical 3D printing

We have already highlighted some key biomedical 3D printing applications, yet the possibilities are limitless. From the development of medical implants to the manufacture of medical equipment, innovations are coming thick and fast. Tissue and organ engineering is a major application of 3D printing, with the fabrication of complex structures such as cartilage, muscle, and skin being explored. Analysis of the CAS Content Collection shows that concepts such as “tissue engineering”, “tissue scaffolding”, and “bioprinting” appear frequently in biomedical 3D printing publications related to tissues and organs, highlighting that this is a key area of research focus (Figure 7).

3D printing technology also has several potential applications in pharmaceutics to help make the elusive goal of personalized medicine a reality. Using biomedical 3D printing, it may be possible to modify and fine-tune the dosage, shape, size, and release characteristics of pharmaceutical products.

Biomedical 3D printing technology has also opened new capabilities in creating prosthetics and implants, with the potential to create prosthetics personalized to the anatomy, color, shape, and size of the patient. Flexible materials have provided more options with body parts and capabilities, while metals like titanium alloy can be utilized in bone reconstruction . Analysis of the CAS Content Collection shows that concepts such as “prosthetic implants”, “prosthetic materials”, and “dental implants” appear frequently in 3D printing publications related to orthopedics and prosthetics (Figure 8). Though there are markedly fewer publications compared with tissues and organs, this is still a dynamic and rapidly growing field.

Challenges in biomedical 3D printing

Though we have seen many exciting advances in biomedical 3D printing, in many areas, the technology is still in the early stages. For instance, researchers have successfully bio-printed vascularized cardiac patches, yet fabricating a robust heart valve (let alone a full-scale organ) is still a long way from being a reality. Currently, 3D printers are simply unable to fabricate tissues with the biomechanics and functionality of the real thing. Advancements in bio-inks and the use of media and stem cells will all likely contribute to the future optimization of these methods.

The future of biomedical 3D printing

If the current research trends are anything to go by, we can expect significant continued investment and innovation in biomedical 3D printing. We predict that the technology will become more widespread, with the concept of 3D printers being used in pharmacies now becoming a near possibility. Though biomedical 3D printing represents a significant financial investment for hospitals, the benefits can far outweigh the costs with the right planning. As the technology grows, there is a need for standardized terminology and the Food and Drug Administration to define a new regulatory framework that ensures the safety and effectiveness of biomedical 3D printing products.

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Due to the environmental impact of CO² emissions, scientists are exploring ways to make fertilizer manufacturing more sustainable. This scientific journal review analyzes the scientific and patent trends on sustainable fertilizers from 2001 through 2021 from the CAS Content Collection^TM. This bibliometric study and literature evaluation will help scientists identify and use new fertilizers and nutrient sources to augment existing ones, while also increasing the effectiveness and sustainability of waste management and ammonia production.

As the world's population continues to grow, the demand for food also increases. While synthetic fertilizers have been valuable, their production and use can have negative impacts on the environment.

Sustainable fertilizers, on the other hand, offer a more environmentally friendly alternative. Explore the emerging landscape of this growing field with unique insights into publication trends, new opportunities, and related challenges.

The key role of sustainable agriculture in global food production

It is predicted that the total global food demand is set to rise by 35–56% between the years 2010 and 2050, compounded by a steady increase in the global population. In recent years, the rising costs of food production and distribution has been affected by the COVID-19 pandemic, the Russia–Ukraine war, climate change, and regional conflicts. The International Monetary Fund has emphasized that policy changes are vital to reduce food insecurity and improve fertilizer access, especially in poorer countries.

Synthetic and organic fertilizers continue to be crucial for sustaining farming practices. Synthetic fertilizers use phosphorus mined from phosphate rocks, potassium mined from potash ores, and nitrogen fixed from atmosphere, yet the processes for the extraction of these resources are energy intensive and thus exert a long-term detrimental impact on the environment through mining activities and use of fossil fuel energy sources in their production. Organic fertilizers include manure from various animals, alfalfa meal, blood meal, fish meal, and wood ash, as well as waste from water or sewage. Manure and other wastes that form organic fertilizers are bulky and expensive to transport for field application or disposal, but nutrients being derived from these types of waste can remove the need for costly transport if they can be processed on-site or near where they are produced.

A sustainable agriculture system involves efficient use of water, energy, and nutrient resources; reducing environmental impact, maintaining economic strength, and minimizing dependence on finite depleting resources, allowing both current and future generations to thrive. An example of how nutrients are recovered, reused, and recycled from wastewater for use in fertilizers is shown in Figure 1.

Fertilizer macronutrients are one such finite depleting resource. For example, phosphate reserves may be depleted within the next 50–100 years . In addition, waste agricultural products may also be harmful to the environment, leading to issues such as contamination of crops with pharmaceutical, pathogen, or metal waste, and eutrophication of surface waters. However, these wastes present significant potential, owing to their high nutrient volume.

On the path to sustainable agriculture: opportunities to harness innovation

The term circular bioeconomy refers to ways of transforming and managing our land, food, health and industrial systems via the management of biological resources to achieve a sustainable wellbeing in harmony with nature. By harnessing innovation in sustainable agriculture, there is significant potential in exploiting the nutrient content in waste products to bolster food production and minimize environmental impact. Commonly used biological, chemical, and physical methods of nutrient recovery are summarized in Table 1. Potentially sustainable methods that have garnered interest in recent years include:

• Smart nano-fertilizers: Nitrogen nanofertilizers are expected to increase Nitrogen Use Efficiency by improving the effectiveness of nitrogen delivery to plants and reducing nitrogen losses to the environment. This can be performed in a number of ways, via reducing fertilizer volume to nanoparticles, supplementing fertilizer with nanomaterials, or forming nanocomposite structures via encapsulation or storage in nanopores to control nutrient release.

• Biorefineries: In comparison to first-generation biorefineries that utilized crops as feedstock, second-generation biorefineries use residual and waste streams. Biomass is converted into liquid fuels and chemical compounds by enzymes and microorganisms using various conversion platforms.

• Biochar (charcoal): While the use of biochar is a relatively novel concept in carbon sequestration, the history of this charcoal-like substance dates back 2000 years to the Amazonian basin, where adding charred biomass to soil was thought to improve soil quality and fertility. Anaerobic pyrolysis of organic matter such as dead plants or leaf litter is a clean and energy-efficient approach to producing a stable form of carbon.

• Green ammonia: This is the process of making ammonia 100% renewable and carbon-free, using renewable energy, nitrogen, and water. Green ammonia synthesis projects that use water electrolysis to supply H2 have been commercialized in recent years by major companies, including Air Products, Siemens, OCP, thyssenkrupp, and Grupo Fertiberia.

• Struvite: Struvite, also known as guanite or magnesium ammonium phosphate (MAP), is a crystal in which Mg²⁺, (NH₄)⁺, and PO₄³- are combined in the molar ratio or stoichiometric proportions of 1:1:1. It can be used either alone or in complex fertilizer formulations with other waste-derived products, microbial inoculants, or conventional inorganic fertilizers. Its high-nutrient composition and slow-release properties make it an attractive candidate for commercial fertilizer production

Table 1. Overview of commonly used nutrient recovery processes from waste

Sustainable agriculture trends in fertilizer research and nutrient recovery

The CAS Content Collection™ is an expert-curated resource that was used to evaluate methods of nutrient recovery and the concepts driving innovation and therefore maintaining our circular bioeconomy. A broad fertilizer search retrieved 121,213 patents and 125,228 journal publications over the 2001–2021 period (Figure 2). Journal-related topics focused on the effects of fertilizers on crop plant growth, biological responses, and soil fertility were studied, with some focusing on processes of recovery of nutrients for fertilizers and nutrients as pollutants that cause the eutrophication of receiving waters, or agricultural wastes and soils containing pollutants. Patent-related topics focused on organic substances and processes associated with fertilizer nutrient recovery, fertilizer formulations, and biowaste topics such as manure, ashes, and fermentation.

A search was performed to identify sustainable agriculture trends for exploiting nitrogen, phosphorus, and potassium as nutrient sources, as well as the processes for their recovery.

In both journals and patents, substance classes such as "organic/inorganic small molecules", "elements", and "salts/compounds" dominated, with "mixtures" also being prevalent in patents.

Biological processes were the most prominent methods for nutrient recovery, accounting for 66% of journal/patent publications, followed by physical methods (22%) and chemical methods (12%).

Key topics of interest focused on nutrient recovery from wastewater treatment sludge, biochar, and ashes. There were notable trends in biochar production, struvite precipitation, and green ammonia synthesis.

A clear increasing trend in charcoal/biochar topics was noted in patents and journals, with journal publications demonstrating continued growth despite a slight drop in 2019. Patent publications around sustainable agriculture have grown, especially since 2013, although the numbers year-over-year have been somewhat variable (Figure 3). A conceptual analysis revealed relationships between “wastewater treatment sludge” and “manure” with “anaerobic biological digestion”.

Struvite publications increased substantially during the period studied. Struvite in the form of [(NH₄)Mg(PO₄).6H₂O] was dominant; very little has been published on potassium struvite [MgK(PO₄).6H₂O] (Figure 4), although some research indicates that it can be recovered with the potential to serve as a magnesium phosphate fertilizer. Key concepts relating to struvite production included "chemical precipitation", "crystallization", "wastewater treatment settling", and "adsorptive wastewater treatment".

Green ammonia was discussed primarily in journal publications, with patent documents reaching 20% of the total publication volume in 2020. There was dramatic growth in substances with a role in catalytic green ammonia synthesis from 2017 to 2021; numbers increased from less than 100 distinct substances in 2017 to nearly 500 distinct substances in 2021. Substances of interest were those that comprise new catalysts used in green ammonia synthesis, e.g., inorganic materials, organic/inorganic small molecules, elements, and co-ordination compounds (Figure 5). Moreover, the proportion of journal publications featuring photocatalytic or electrocatalytic nitrogen reduction grew from 1% in 2001 to 25% in 2021, highlighting the rapid advancement of this method.

Is climate-resilient agriculture on the horizon?

With a burgeoning global population comes mounting pressures on the agrifood industry. Both fertilizer production and the accumulation of agricultural wastes are contributing to irreversible environmental damage. Sustainability and the concept of a circular bioeconomy have become a core principle of responsible farming practice. Principles of sustainable agriculture have inspired research into the development of integrated systems for waste treatment, nutrient recovery, and energy efficiency.

Alternative “greener” processes for fertilizer production, such as green ammonia synthesis and the recovery of fertilizer nutrients from waste and microbial formulations, have the potential to change the way our food is produced and can convert waste into valuable by-products.

Nutrient recovery processes are being commercialized to help streamline efficiencies, reduce costs, and minimize environmental impact. Some notable sustainable agriculture technologies include:

• Pearl® and WASSTRIP® (Waste Activated Sludge Stripping to Remove Internal Phosphorus) technologies (Ostara Nutrient Recovery Technologies Inc., Canada) are key processes for phosphorus removal used to produce Crystal Green®, a sustainably recovered slow-release fertilizer containing phosphorus, nitrogen, and magnesium. The Root-Activated™ release optimizes uptake and protects local water resources, while increasing yield.

• AirPrex® (CNP CYCLES GmbH, Germany) is a patented sludge optimization process that improves biological phosphate elimination. In the AirPrex® reactor, digested sludge is treated to ultimately lead to precipitation of MAP, or struvite, which can be used as fertilizer.

• AshDec® Thermochemical P-Recovery system (Metso Outotec, Finland) improves plant availability and reduces heavy metal content through recovery of phosphorus from sewage sludge ash. The phosphorus product is citrate soluble, and hence environmentally friendly. Furthermore, phosphorus release is controlled — it only takes place in the presence of crop root exudates.

• The RecoPhos Project (The RecoPhos Consortium) is a multidisciplinary project undertaken by academia, industry, and enterprise. The objective is to recover phosphorus (as white phosphorus or phosphoric acid) from sewage, sludge, and ashes using an innovative reactor. This work will provide the basis for implementing a fully operational bench scale reactor and the design of a pilot scale plant. The economic, environmental, and social impact of the RecoPhos process will also be evaluated.

• The Aqua2™N Process (Easymining Services, Sweden) recovers nitrogen from sludge liquor. Nitrogen is adsorbed and harvested as crystals, which is then recovered as in a form that is readily applicable for fertilizer production. The absorption agent can simply be used again.

Initiatives such as these are proof that cross-sector collaboration amongst science, technology, and industry is the way forward to not only overcome challenges with food production, but also streamline waste recovery. Sustainable agriculture presents a sure way to future-proof our society.

Learn more about sustainable agriculture trends in nutrient recovery processes in our Insight Report.

In the past few years, the discovery of microplastics and their impact on the environment has been staggering. Microplastics have been found almost everywhere from food, oceans, and even air and can take hundreds of years to break down.

Learn more about the past publication trends, what can be done, new approaches and alternatives that are beginning to gain traction in our latest scientific publication here.

Microplastics are small plastic particles that are less than 5mm in size. They can come from a variety of sources, including the breakdown of larger plastic items, the shedding of synthetic fabrics, and the use of microbeads in personal care products.

While microplastics may be small, they can have a big impact on the environment. They can be ingested by marine life, which can lead to injury or death. They can also accumulate toxins, which can then be passed up the food chain to humans. In addition, microplastics can take hundreds of years to break down, meaning they can persist in the environment for a long time.

Learn more about the emerging landscape of microplastics pollution, the opportunities and new approaches that are gaining traction, and alternative materials in our latest Insight Report.

From shower to sea: waking up to the dangers of microplastics

Plastic pollution has become a substantial global problem, and one that is causing irreversible environmental damage. Microplastic particles (or microplastics), pieces of plastic measuring between 1 μm and 5 mm, are emerging contaminants that are generating intense concern. A 2022 World Health Organization (WHO) report on microplastic exposure highlights the ubiquitous nature of microplastics, which have been documented in our seas, air, soil, and food and drink.

Microplastics can be generated from primary or secondary sources. Primary microplastics are less than 5 mm in size, and sources include microbeads from cosmetics and cleaning agents, and microfibers from synthetic textiles. Secondary microplastics are formed from the breakdown of larger plastic particles and are more heterogeneous with regards to their size and composition. Examples of secondary microplastics include debris from vehicle tires, particles released from paint, road markings, marine coatings, and microfibers.

Assessing the sources, creation, and fate of microplastics is important to understand why they are so common in the environment (Figure 1). By considering a lifecycle approach to plastic, it allows the identification of key hotspots for both the production and consumption system, which takes into account the potential impact, caused by plastic products at each stage, on:

• Climate
• Ecosystems
• Health
• Economy

Microplastics can be taken in by organisms via ingestion, inhalation, or skin exposure. Microplastics and their associated chemicals and additives are thought to exert numerous negative effects on our health in areas such as chronic inflammatory diseases and cancer. Evidence on the effect of microplastics on marine life ranges from reduced feeding and photosynthesis to reduced reproduction. Microplastics can even carry toxic compounds and metals, which may cause further harm.

The alarm is finally sounding. It’s time for us to wake up to the threats associated with microplastics. Is enough being done to tackle this seemingly insurmountable problem?

Publication trends of microplastics

An analysis of data from the CAS Content Collection™ relating to microplastics, microfibers, and associated topics resulted in a final pool of almost 9,500 articles. Key trends in publications showed a more than 30-fold increase in microplastics publications in the ten-year period from 2011 (n=81) to 2021 (n=2,811), while the number of patents has remained stable during the same period (Figure 2).

CAS data reveals that the countries leading the way in publishing literature linked to microplastics are China, followed by the US, Germany, South Korea, and Italy (Figure 3).

The top five substances registered in microplastic research were shown to be ethene homopolymer (polyethylene), polystyrene, 1-propene homopolymer (polypropylene), polyethylene terephthalate (PET), and polyvinyl chloride (PVC; Figure 4). Cellulose was another prominent substance featured in the findings – paradoxically, owing to its use as a polymer replacement (in applications such as electronics, biomedicine, and microplastic removal), and its presence in cellophane and rayon fibers as a microplastic — in the form of regenerated cellulose.

Rising to the microplastics challenge

The question that remains is this: what can be done to combat microplastics in the natural environment? Methods proposed specifically for microplastic removal from marine environments include the exploitation of ship systems, waste collecting systems, and even mussels, whose feces, owing to the plastic component, float on the water's surface. However, water collection methods can be difficult and efforts to directly remove existing microplastics in this way have been limited.

Feasible approaches to stop microplastics from entering the environment include the use of wastewater treatment plants, laundry accessories in washing machines to capture microfibers, and altering clothes manufacturing processes to minimize friction or to improve the mechanical integrity of garments.

Popular keywords relating to microplastic removal in the CAS publications analysis included ‘filtration’, ‘wastewater plants (WWTP)’, and ‘membrane bioreactor (MBR)’ (Figure 5). Publication volumes featuring most of the keywords grew significantly since the mid-2010s, suggesting that there was an immediate reaction to the problem, and removal-related research efforts appeared to increase at a pace similar to microplastic research in general.

What is perhaps most important is that we mitigate our plastic use in general. Biodegradable or sustainable alternatives, such as shampoo bars and bamboo sponges, along with zero-waste shops and ethical fashion brands, are all growing in popularity.

The combat against microplastic pollution will require long-term dedication and concerted efforts among scientists, researchers, entrepreneurs, governments, and the public. Barriers to microplastic removal efforts include shortcomings with existing data according to the WHO, where the quality of evidence is not considered robust.

More field and laboratory research must be undertaken to characterize the true effects of microplastics on health, including their retainment in and elimination from tissues, along with their binding activity. Refining analytical tools that can detect smaller particles (nanoplastics) is another top priority.

While experts recognize the myriad ways in which we can tackle the microplastics problem, funding for microplastic removal, and the lack of associated profitability, presents a key challenge. Financial assistance and ramping up regulatory laws on plastic use will help accelerate progress toward a more sustainable plastics economy, and a cleaner, healthier future. Read more on this topic in our Microplastics Insight Report.