Pharmaceutical design is currently based on the Quality by Design (QbD) concept, a new, systematic, risk-based methodology. QbD begins with predefined objectives and dwells on product and process understanding, along with process control [77,78,79,80]. QbD requires: (i) knowledge of the physiologic barriers NPs face within the human body, (ii) complete characterization of NPs materials, and (iii) fully understanding of the NP synthesis process.
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The US National Cancer Institute has pointed out that most engineered NPs are far less toxic than household cleaning products, insecticides used on family pets, or over-the-counter dandruff remedies, which are present at order-of-magnitude higher levels than the engineered NPs [ 89 ]. Moreover, in their use as carriers of chemotherapeutics in cancer treatment, engineered NPs are much less toxic than the drugs they carry.
As to toxicity, amorphous silica solubility (~120–170 ppm, at the temperature and pH of the body fluids, 36–37 °C and 7.35–7.45, respectively), allowed an easier silica elimination (as silicic or poly(silicic) acid) which are non-toxic and diffuse through the blood stream or the lymphatic system to be eventually cleared in the urine, preventing its accumulation in kidneys, liver or spleen (contrary to the crystalline polymorphs counterparts) [ 87 , 88 ]. Amorphous silica phases lacked the regular long-range order purposed by the classical crystal growth and dissolution models which difficult the understanding of its dissolution mechanism. Yet, a-SiO 2 phases shared with the silica crystalline polymorphs the fundamental unit, the (SiO 4 ) 4− tetrahedron, and short range structural order (at length scales up to 20 Å), despite variations in Si-O-Si bond lengths and angles. The a-SiO 2 atomic scale disorder enabled the loss of surface (SiO 4 ) 4− Q 3 units into solution (creating vacancy islands) and keeping unchanged the a-SiO 2 surface Gibbs energy. As a consequence, dissolution rates of amorphous silica phases, which involves an equilibrium between the solid phase and dissolve monomer Si(OH) 4 , scaled linearly with increasing driving force (undersaturation). At pH values above 8, the presence of [H 3 SiO 4 ] ion in addition to Si(OH) 4 is responsible for the high silica solubility at this pH values (as the concentration of Si(OH) 4 in equilibrium with the solid silica phase is not pH dependent).
Several methods have been developed to mask or camouflage NPs from the MPS or renal clearance. The most preferred of these methods is the adsorption or grafting of poly (ethylene glycol) (PEG) to the surface of NPs. Addition of PEG and PEG-containing copolymers to the surface of NPs resulted in an increase in the blood circulation half-life of the NPs by several orders of magnitude. This method created a hydrophilic protective layer around the NPs that is able to repel the absorption of opsonin proteins via steric hindrance, thereby blocking and delaying the first step in the opsonization process [ 81 ]. Moreover, PEGylation prevents NPs aggregation in solution, which helps keep them from forming a cluster once in blood vessels, where they could otherwise embolize and occlude blood flow resulting in microinfarctions at distant sites and organs.
Renal clearance (based on physical filtration, dialysis) is a second optimal method for expelling NPs from the body. As a first approximation, removal by the renal system occurs only for polymeric molecules with a molecular weight of around 5000 or less, or inorganic NPs with hydrodynamic diameters smaller than 8 nm. Dendrimers (with molecular weights as high as 100,000) and NPs larger than 8 nm (if somehow broken down into fragments smaller than 6 nm after drug release) may also be cleared by the renal system [ 86 ]. Non-biodegradable NPs and degradation molecules with a molecular weight higher than the renal threshold typically become sequestered in the MPS organs ( ).
Finally clearance occurs. The phagocytes begin to secret enzymes and other oxidative molecules (like superoxides, oxyhalide molecules, nitric oxide, and hydrogen peroxide) to ingest (chemically break down) the phagocytosed material [ 81 ]. Unfortunately, most non-biodegradable NPs cannot be degraded significantly by this process and, depending on their relative size and molecular weight will either be removed by the renal system or sequestered and stored in one of the mononuclear phagocyte system (MPS) organs.
After opsonization, phagocytosis occurs. Macrophages (typically Kupffer cells of the liver or spleen) cannot directly identify the NPs themselves, but rather recognize (through specific, non-specific receptors or complement activation) opsonin proteins adsorbed to the NPs surface [ 81 ]. Macrophages may uptake foreign materials within a matter of minutes (after opsonization), increasing the phagocytosis rate for positively charged and bacteria-specific proteins and render them ineffective as nanocarriers [ 83 ].
Opsonization is the process by which a foreign organism or particle becomes covered with biologic proteins (opsonins), forming a coating (named corona by materials scientists or opsonins in pharmaceutics) thereby making it more visible to phagocytic cells. The exact mechanism through which opsonization is activated is complex and is not yet fully understood. When the opsonin proteins (blood serum components like laminin, fibronectin, C-reactive protein, type I collagen, components of the complement proteins such as C3, C4, and C5 and immunoglobulins [ 81 , 82 ]) come into close contact with engineered NPs, typically by random Brownian motion, they may adsorb on NPs surface through van der Walls, electrostatic, ionic or hydrophobic/hydrophilic attractive forces. Protein opsonization usually takes place in the blood circulation system and may hold from few seconds to many days to complete.
The biological performance (pharmacokinetics profiles, biodistribution, target recognition, therapeutic efficacy, inflammatory reactions and toxicity) of intravenously injected NPs is controlled by a complex array of interrelated physicochemical and biological factors, starting with opsonization, followed by phagocyte ingestion and ending with NPs clearance. [ 81 , 82 , 83 , 84 ]. Rapid blood clearance limits drugs/gene/therapeutic molecules/markers accumulation at target delivery sites, while NPs accumulation in macrophages (within clearance organs) initiates inflammatory responses, inducing toxicity [ 85 ].
As regards the renal system, neutral surface charge gives the highest chance to pass through renal filtration (and being excreted in urine), while both positively and negatively charged NPs adsorbed more serum proteins, increasing their hydrodynamic diameter and thus reducing their ability to be eliminated [ 91 ]. Unlike the long time clearance process taken by bile (or other MPS organs), the renal system removes the NPs from the body through the urine, with minimal side effects [ 88 ].
NPs may differ in surface chemical composition, a critical parameter in determining their drug-loading efficiency, releasing profile, circulation half-life, tumor targeting and clearance from the body. A hydrophilic surface makes the NPs more resistant to the plasma proteins adsorption (preventing the formation of corona) and thus avoiding their recognition and uptake by the MPS. Coating the NP surface with a hydrophilic polymer (like PEG) or directly synthesizing NPs with hydrophilic surface compounds (in situ synthesis) are two strategies to overcome the challenge. Rapid opsonization and clearance is observed for NPs with excess positive surface charges [ 90 ].
As to shape, NPs may exhibit an extensive range of geometries—from spherical to tubular, through centric, eccentric and star like. While spherical NPs are good candidates for drug delivery, anisotropic structures can sometimes provide higher efficiencies in drug deliver (due to a more favorable configuration with the cell), although the sharp edges and corners may induce injuries to blood vessels. NPs may be hollow, dense, nanostructured, or in core-shell (eventually with multiple cores) structures, enhancing the NP load capacity and specific targeting ability.
As far as size is concerned, NPs may exhibit different size profiles and different shell thicknesses (in core-shell structures), showing in all cases an outstanding surface-to-volume ratio, responsible for an extremely active/reactive surface performance. Size determines in vivo distribution, intracellular uptake, toxicity, and targeting ability, influencing drug loading, drug release, and in vivo and in vitro stability. Smaller particles have a great risk of aggregation during storage and incubation in vitro, but have higher mobility and longer circulation half-life in vivo. To run an effective and reproducible biomedical NPs system, monosized distribution is required, usually between 10 and less than 200 nm.
During the last decades, remarkable efforts have been made to develop novel NPs synthesis methodologies. Today, it is generally accepted that nanosize cannot be efficiently achieved by the traditional top-down methodologies (such as ball milling and lithography) but rather by bottom-up techniques. A bottom-up strategy looks faster, precise, and cost-effective.
A bottom-up strategy holds a large number of techniques (flame spray pyrolysis, chemical vapor deposition, and wet-chemistry methodologies like co-precipitation, hydrothermal, solvothermal and sol-gel) but research has been focused on sol-gel, as the synthesis is straightforward, scalable, easily controllable, time and energy saving. The sol-gel chemistry comprises chemical reactions involving colloidal particles in a sol, or between alkoxide-precursors and water, in a solution, leading to a highly porous amorphous gel product, in which a liquid phase (solvent, catalyst and eventually excess reactants) may be retained in bulks (3D), films (2D), fibers (1D), powders, and NPs (0D) products [39,92]. The sol-gel SiO2 NPs synthesis comprises four common methods: (i) colloidal routes, (ii) biomimetic syntheses, (iii) solution routes (base- and acid catalyzed)) and (iv) templated syntheses (the last one dedicated to mesoporous silica NPs, a topic outside the scope of this short review).
In colloidal routes, sol-gel SiO2 NPs are formed in an aqueous medium through the supersaturation, polymerization and (eventual) precipitation of silica polymorphs. In the geological world silica NPs of ~1 nm (basically orthosilicic acid, a weakly acidic molecule with pKa ~9.8) undergo rapid growth to 2–4 nm, at pH 2–3 (as pHPZC ~2.2; ζ ~0 mV at pH ~2–3, facilitating NPs growth). As silica solubility increases well above pH 7 particles grow up to 4–6 µm by coalescence and Ostwald ripening (pH >> pHPZC, and ζ < −30 mV). At pH > 9 (the ionized form of monomeric silicic acid Si(OH)3O− predominates) silica NPs cement to form a bulk gel, originating opal-like structures [38,39]. Ostwald ripening of silica particles originates from surface instability of silicon dioxide and is driven by differences in chemical potential between particles of different size and shape. The local radius of curvature and ratio of surface area to volume accounts for the particle’s surface energy, which is greater in the case of small particles or those with rough surfaces. Under kinetically favorable conditions these high surface energy particles dissolve preferentially, with the material being deposited onto particles with the largest radius. Silica dissolution proceeds via cleavage of siloxane bonds on the NPs’ surface (which is faster in amorphous structures), resulting in the release of soluble silicic acid ( ).
Open in a separate windowCommercial precipitated silica, formed from sodium silicate solution and sulfuric acid, has the largest share of global market of silica particles (in classical industries), a position that is expected to grow in the next decade [2,3,4].
In the biological world plants, diatoms and sponges are capable of accumulating, storing and processing Si to create biogenic silica (at mild ambient conditions and under-saturated aqueous solutions of silicic acid). Several factors affected the process of natural silica condensation, namely concentration of silicic acid, temperature, pH, and the concentration of co-precipitating/nucleating agents (external small molecules and polymers) [93]. Plants started by taking up Si in the form of Si(OH)4] or Si(OH)3O− (present in soils at concentrations as low as few mg kg−1). When the silicic acid concentration is in excess of 100–200 mg kg−1, polycondensation reactions occur at final location, forming silica polymers equal or higher in size than the critical nuclei size. The viable nuclei grow to form spherical NPs, as the absence of crystallographic patterns promotes isotropic spherical growth. The final SiO2 NPs are amorphous at the 1-nm length scale [94], built up from SiO4 tetrahedron with variable Si-O-Si angles and Si-O bond distances. However, a great variety of medium/long range order patterns may be found in nature (branched chains, structural motifs or even hierarchical patterned structures) resulting in different density, hardness, solubility, viscosity and composition values [54,55,93]. As the silica NPs reach 1–3 nm in size, they interact with plant cell walls (due to the negatively charged silica NPs surfaces, at neutral pH).
As to diatoms, there are more than 105 species with unique frustule architectures ( ). The micro- and nano-sized diatoms can be also produced by cultivation, and here purification and chemical modification protocols are well established to generate pure active biohybrid materials [95]. Furthermore, the production of diatoms is environmentally friendly (compared to synthetic silica-based NPs), due to absence of toxic waste products and low energy consumption. Diatoms are considered to be harmless thanks to the amorphous silica structure [96], and food grade diatomaceous earth has been approved in the USA to feed animals and there are already several human grade diatomite silica microparticles products on the market in Europe and Australia [97]. The potential of silica diatoms for oral drug delivery applications, in intestinal (pH 7.2) and simulated GIT (pH 1.2–7.4) fluids [98,99,100] was recently demonstrated ( ).
Open in a separate windowMimetic natural SiO2 production is gaining ground, and represents a source of inspiration for green eco-production processes. In biomimetic silica synthesis particle formation can occur by the use of certain co-precipitating/nucleating (biologic or biomimetic) agents, under neutral or acidic conditions. As research on the biogenic silica production has progressed, key molecules (such as silicateins, silaffin R5, proteins, peptides, carbohydrates, lipids, metal ions and phenolic compounds) that participate in the silicification of microorganisms have been found. Several studies have identified alternate amine-molecules as candidates for inducing silica precipitation from precursor compounds in vitro. These amine groups thus impart the silica with a strong positive surface charge (populated with -NH3+ groups, ζ ≥ 30 mV) in acid and neutral pH, thus stabilizing the silica sol and allowing the NPs growth through Ostwald ripening [113,114]. Spherical porphyrin-functionalized SiO2 NPs were biomimetically synthesized with diameters between 50 nm and 800 nm. However, high quality silica NPs with a diameter less than 50 nm still remains a long term challenge [115,116,117,118]. Nearly monodisperse SiO2 NPs, with tunable size between 10 nm and 200 nm, were synthesized in aqueous media by using lysine [119,120] and arginine [121,122] as base catalysis. Cationic block copolymer micelles [123] and cationic poly(acrylamine-co-2-(dimethylamine) ethyl methacrylate, methyl chloride quaternized) (poly (AM-co-DMC)) [124] and polyalylamine hydrochloride (PAH) [125] were used as colloidal template for the biomimetic deposition of 35 nm silica NPs. Protein immobilization (biomolecules encapsulation) within biomimetic silica NPs has been investigated for a wide variety of enzymes [126,127,128,129,130], bovine serum albumin (BSA) protein [131] and has even proved successful for the entrapment of different enzymatic proteins [132].
The solution route is the most common sol-gel synthesis process. Here metallic salts, metal alkoxides, or other organometallic precursors undergo hydrolysis and condensation, to form a wide range of sol-gel products. The right choice of catalyst, pH, water to silica precursor’s ratio (to control hydrolysis rate), type of solvent and solvent to water ratio (to enhance reactants mixing), type of silicon precursor (as R may have inductive and steric effects on hydrolysis rate), the presence of chelating agent (to control the relative hydrolysis to condensation rate) and finally the temperature, allow the control of SiO2 structure, size and/or morphology ( ). Due to the hydrophobic nature of the alkyl groups organometallic precursors and water are not miscible, and the addition of a common solvent (usually an alcohol) becomes mandatory to promote miscibility between reactants. In the case of silica synthesis, the low polarity of the Si-O bond in silicon alkoxide (the Si atom bear δ+ = 0.32 low positive charge in TEOS) is responsible for the slow sol-gel progress, rendering catalysis essential.
Open in a separate windowSol-gel basic conditions confer negative surface charges to the silica monomers (pH >> pHPZC, and ζ ≤ −30 mV), which (kinetically) stabilize the silica suspension, allowing the formation of NPs. Above pH 7, maximum NPs growth is achieved, as a consequence of the increase in silica solubility, which promotes depolymerization of siloxane bonds, and produces monomeric silica necessary for the aging process. As to NPs, Stöber developed a mild synthetic protocol (room temperature, pH ~9–11) for growing (quasi)monodispersed spherical NPs (with diameters between 50 nm and 2 mm) based on sol-gel silicon alkoxides and sodium silicate solution (SSS) as seeds ( ). An alkoxide precursor (such as TEOS) is hydrolyzed (in an ethanol solution) to produce silicic acid, which then undergoes a condensation reaction to form amorphous silica NPs. Arkhireeva and Hay [133] obtained sub-200 nm NPs by slightly modifying the Stöber method. On the other hand, synthesized SiO2 NPs (in sub-100 nm size range) present high polydispersity and irregular shape. Zou et al. [30] proposed a procedure to produce monodisperse spherical SiO2 NPs with sizes ranging between 30–100 nm, based in the classical two-dimensional LaMer [134] model. The strategy is built upon an effective selection of reaction conditions for the Stöber method, and relies on a modification of the conceptual classical LaMer model of nucleation and particle growth. The LaMer methodology, supported on the protocols by Arkhireeva et al. [133] allow the synthesis of NPs at room temperature in less than 1 h.
Open in a separate windowGenerally acid conditions favor the production of gels, as the silica formed in acid solutions possesses little or no surface charge (zeta potential will be in the tricky range of ζ < |30 eV|, PZC silica ~ pH = 2.2) facilitating flocculation/connectivity between silica species. Here the hydrolysis step is typically the fastest, but condensation begins before hydrolysis is complete. Condensation often occurs in terminal silanols, resulting in chain like structures in the sol and network-like gels. Linear or highly branched polymeric species are formed, given rise to 3D structures.
To synthetize SiO2 NPs under acid-catalyzed process a reverse-micelle (or water-in-oil microemulsion) system is formed by adding water, oil and surfactant. The hydrolysis and condensation reactions will develop in the confined reaction vessels (formed by the dispersed aqueous phase in the continuous oil matrix ( )). The confined nanoreactor environment is shown to yield highly monodisperse NPs and allow the incorporation of non-bonded non-polar molecules, which are often difficult to incorporate into the hydrophilic silica matrix. In the last few years, several dye-doped SiO2 NPs have been synthesized by the reverse microemulsion technique in which polar dye molecules are used to ensure successfully encapsulation into SiO2 NPs [135].
Open in a separate windowThe reverse microemulsion process is widely used in silica NPs synthesis. However, besides having low yields, the reverse microemulsion process uses a large amount of potentially toxic surfactants and organic solvents, and demands previous washing to biological application, in order to avoid disruption or lyses of biomembranes. The Stöber’s method arises as more eco-friendly alternative, in which the hydrolysis and condensation of a mixture of alkoxysilanes takes place in mild basic aqueous medium, to create monodisperse, spherical, electrostatically-stabilized particles. Recently (ammonia free) Stöber silica NPs were synthesized under basic catalyzed ensured by hydrothermal water (SPA Cabeço de Vide, Portugal, pH ~11) [136].
The Stöber method is a promising method for producing surfactant free silica NPs or coatings; yet the final particles size remain in the hundreds of nanometers to micron regime, which are too large to some of the biological studies. LaMer alternative allows the control of particles size and dispersion, but a regular shape (silica NPs < 100 nm) is still difficult to obtain. NPs prepared through the microemulsion method, exhibited smooth surfaces and low polydispersity. However, for use in biomedicine, the microemulsion method is not as safe as the Stöber one; the use of surfactants in the NPs synthesis carries a higher risk of cytotoxicity.
Stöber silica NPs are largely used in oral applications on account of their chemical stability and intrinsic hydrophilicity, being thus appropriate for biological environments. AEROPERL® 300 Pharma (particle size of 30 mm) is used in formulations of hesperidin oral delivery carrier [137], hydrophylic Aerosil 380 (7 nm in size) is used to stabilize Pickering emulsions in lipid-based oral delivery systems [138,139,140]. Oral insulin bioavailability was tested in a SiO2 nanoplatform (silica NPs associated with insulin and then coated with mucoadhesive polymer, like chitosan or PEG) [100,102] ( ).
Sol-gel allows in situ incorporation of a variety of functional (non-hydrolysable) organic groups within the silica matrix, in order to increase their biocompatibility, improve its resistance to enzymatic action, internalization efficiency and gene targeting (either in Stöber or reverse emulsion methods). The ORganically MOdified SILica matrix (known as ORMOSIL [141,142]) is an alternative material with even better and more versatile properties than silica: the presence of non-hydrolysable organic groups in the alkoxisilane precursors makes these behave like glass modifiers, reducing the degree of silica network cross-linking as well as increasing the network flexibility as the unhydrolyzed—Si-R bond apparently dangles, causing higher mobility during gelation and undergoing weaker contraction during drying. A tunable wettability, by a judicious choice of the ratio of hydrophilic to hydrophobic sol-gel precursor monomers, a tailor made porosity (size and shape) and a shell hardness/complacency making ORMOSIL a very competitive material. Furthermore, ORMOSIL NPs surfaces will be populated with both silanol and non-hydrolysable organic groups, allowing an easier chemical conjugation/decoration of biomolecules at the NPs surface and/or be loaded with either hydrophilic or hydrophobic drugs or dyes. Mammalian cells take up and internalize easily silica/ORMOSIL NPs (without any cytotoxic effect) opening the door to its use in health science [143].
Among the commonly used functionalizing groups, amine (–NH2) is the first choice when gene transfection is designed for gene therapy or vaccination. The –NH2 groups electrostatically interact with proteins, enhancing their absorption, biding and protecting pDNA from enzymatic digestion allowing cell transfection in vitro. ORMOSIL NPs have great potential in DNA delivery; ORMOSIL transfection efficiency was equal to or even better than Herpes Simplex Virus-1 (HSV-1)) and does not cause any damage to the tissue nor has immunological side effects that have commonly been observed with viral-mediated gene delivery [144]. ORMOSIL NPs crossed the blood brain barrier (BBB) in fruit fly insects [145] where no toxic effects on the whole insect organism or their neuronal cells were observed. Biodistribution and clearance in vivo studies (mice) using ORMOSIL NPs showed a greater accumulation in liver, spleen and stomach than in kidney, heart and lungs. Although, clearance studies carried out over 15 days period indicated hepatobiliary excretion of the NPs in the same mice [146].
Core-shell structures have great potential in future biomedical applications, since they constitute a scaffold to create multifunctional NPs, applied to several medical fields, from theranosis to gene delivery performance. Sol-gel Stöber method, by simply replacing the nucleating agent SSS (commonly used in the synthesis of plain SiO2 NPs) by another nanosized system, enables its coating. Superparamagnetic iron oxide NPs (SPIONs) [48], and liposomes [147] are selected nanosystems, due to their academic and industrial relevance ( ).
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SPIONs, the only clinically approved metal oxide NPs [48], have an excellent response to external magnetic fields. However, administration route and SPIONs surface properties dictate their ultimate effect in terms of the efficiency of cellular uptake, biodistribution, and potential toxicity. SPIONs with hydrophobic surfaces are rapidly and efficiently opsonized and cleared from mammal’s circulation system, while SPIONs with hydrophilic surfaces resist these processes being slowly cleared. Silica/ORMOSIL coating emerge as an interesting coating material, granting hydrophilic surface properties, decreasing SPIONs high aggregation tendency, protecting SPIONs from oxidation and thus increasing their blood circulation time [148].
Liposomes are excellent carriers due to their capacity to load hydrophilic and/or hydrophobic molecules, to penetrate in altered vasculatures (due to pathological situations like in cancer or inflammation), to drug release at target sites (over prolonged periods which may vary from hours to weeks) [149]. In clinic, for intravenous administration, there are already several pharmaceutical systems where drugs are encapsulated in liposomal structure. However, when oral administration is envisaged and gastrointestinal tract mucus and epithelium barrier need to be overcome, the protection of liposomes from anticipated disruption becomes a promising strategy [150]. The emerging of silica-based drug delivery carriers for oral route administration was the leitmotiv for silica-coating of liposomes, LIPOSIL for short [151].
Simply silica hollow-sphere NPs (another core-shell possibility) are capable of carrying large amounts of payload or fill their cores with other desirable materials such as polymers, gold or silver along with the gene delivery performance. They can be created through the condensation of alkoxysilanes onto polymer based templates, metal organic frameworks or other nanomaterials, lately removed by chemical etching or thermal degradation [150].
Template synthesis is dedicated to the production of mesoporous materials, topic out of the scope of this short review. A very short summary of synthesis process is presented. The seminal work conducted by researchers at the Mobil Oil Corporation in the early 1990s on the synthesis of mesoporous silicates has led to a number of syntheses in which surfactants are used as templates [152]. Ordered mesoporous materials are unique materials that are defined by an ordered and repetitive mesostructured of pores and disordered arrangement at the atomic level. Their synthesis is based on the use of surfactants that act as templates to direct the morphology of the final amorphous material. Simply, the synthesis process starts with the dissolution of surfactant molecules into polar solvents to yield liquid crystal suspensions. The pair surfactant/solvent defines the working phase diagram. When the surfactant concentration is above the critical micellar concentration (CMC) then the surfactant molecules self-assembly into micelles. Higher surfactant concentrations allow the formation of micellar cubic, hexagonal or lamellar self-assembly structures. Once the (liquid crystal) aggregates are formed, the silica precursors are added to the suspension, the sol-gel reactions occurs and a mesoporous silica material is produced. Finally, the surfactant is removed by chemical or thermal degradation [29] ( ).
Open in a separate windowA definite breakthrough in drug delivery was the use of mesoporous silica NPs to host drugs/therapeutic-molecules/markers. A correct selection of the mesoporous design depends on the molecule to be hosted, and is the first criterion used. The most used mesoporous silica NPs in drug or bioencapsulation are MCM-41 and SBA-15. The synthesis of MCM-41 (from the Mobil Composition of Matter series) involves liquid crystal templating commonly cetyl trimethylammonium bromide (CTAB) that lead to a 2D hexagonal pore channel array with 3.6 nm in size. The diameters of MCM-41 NPs can be controlled in a size range from 25 nm to 100–150 nm. The SBA-15 (Santa Barbara type) is also largely used as biocarrier. This type of mesoporous silica material is prepared by cooperative self-assembly with a pluronic P123 (a non-ionic block co-polymer). The channels adopt also a 2D hexagonal packing with a diameter varying from 6 to 10 nm depending on the synthesis conditions.
The release of the drug from the host mesoporous NP is definitely the big challenge. This may occur through diffusion all through the pore channels (in passive drug delivery) or released under specific stimuli as pH, temperature, ultra-sons or light (in stimuli-responsive systems). Although an impressive variety of mesoporous NPs have design, synthesized and (in vitro and in vivo) tested no products have reached the market so far.
Reshored c-Si PV manufacturing tackles logistic challenges, but whether it directly reduces GHG emissions and energy use has not yet been discovered based on quantitative analysis. Exploring the climate change and energy impacts help us understand if reshored manufacturing aligns with the climate target. We perform a comparative and prospective life cycle assessment (LCA) study of several reshored manufacturing scenarios and outsourced manufacturing cases to examine the energy and climate impacts of fully eliminating dependence on foreign PV supplies. We define three cases (2010, 2015, 2020 offshore manufacturing) and seven scenarios (2020, 2025, 2030, 2035, 2040, 2045, 2050 reshored manufacturing). The reshored scenario in 2020 is studied to examine the climate impacts of solely bringing manufacturing back to the U.S. by comparing it with the outsourced manufacturing case in 2020. Moreover, reshored scenarios from 2025 to 2050 in 5-year increments are forecasted with cleaner power compositions such as wind, solar, geothermal, etc., building up from 21% renewable power contribution in 2020 to 42% in 20508. We project and examine future scenarios spanning a wide range of time points from the near term to mid-century because of the potential uncertainties regarding the speed of domestic PV production scaling and the rate of equipment and workforce training expansion. Past studies expressed concern that trade restrictions and emphases on reshoring might slow the adoption of sustainable energy technologies, and the U.S. might not be fully equipped for rapidly upscaling domestic solar panel production23,24. Trade wars may also affect the environment by altering the global supply and consumption systems25,26, which become less conducive for less-developed regions to transition to clean energy27. Manufacturing efforts face an unpredictable future, and uncertainties remain regarding exactly when the reshoring of PV panels can be accomplished due to trade barriers, financing problems, workforce limitations, and so on. That is why multiple future reshored manufacturing scenarios at different time points, ranging from 2025 to 2050, are included in this study. These projections of different reshoring levels at various time points can be regarded as a sensitivity analysis to incorporate the temporal variations for when reshoring can be achieved. We study reshored manufacturing scenarios because legislations not only include targeted tax incentives aimed at manufacturing U.S.-sourced solar materials but also include key requirements around domestic sourcing. The Inflation Reduction Act opens up an opportunity for spurring U.S. solar technology supply chain as countries around the world race to lead the clean energy economy28,29. Reasonable predictions for these scenarios are made regarding the U.S.-centered domestic supplies as we foresee opportunities to grow a competitive supply chain of module components in regions like Alabama, Florida, Georgia, and so on30. We also study outsourced manufacturing cases in 2010 and 2015 to understand the impacts of the ever-changing global PV module supply chain structure on decarbonization.
For PV power plants, the majority of GHGs are emitted upstream of module manufacturing31. Solar panels do not produce emissions while generating electricity, but the operations and maintenance life cycle stage and the end-of-life treatment stage are included in this study to emphasize the relative emission reductions from panel manufacturing reshoring in the context of PV panel lifetime emissions. The operation and maintenance life cycle phase involves tasks like module cleaning, preventive maintenance (such as replacing inverters), as well as the repair of broken components, and the end-of-life treatment stage involves dismantling and shredding solar panels32. Based on the best available data33,34, a 1 m2 PV panel emits 0.27 kg CO2 eq GHG and demands 48 MJ of energy during its use stage, and emits 0.57 kg CO2 eq GHG and demands 74 MJ of energy at its end-of-life treatment stage. The energy and environmental impacts of the operations and maintenance life cycle stage and the end-of-life treatment stage can be useful to understand the relative emission reductions from PV panel manufacturing in the overall context of PV panel life cycle.
In this study, climate change mitigation potential and energy performance of PV panel manufacturing are presented to study the energy and decarbonization impacts of reshoring on solar panel production. The quantitative analysis is conducted based on two important climate-related metrics, global warming potential (GWP) and cumulative energy demand (CED)35. To investigate the impact of switching from offshore manufacturing to domestic production on the c-Si PV panels, we compare the reshored scenario (Fig. 1b, d, f) in 2020 with the outsourced case (Fig. 1a, c, e) in the same year. Figure 1a, c, and e present the GHG emissions for production across the entire supply chain for each trading partner (China, Malaysia, Japan, etc.) from silica sand production to panel manufacturing between 2010 and 2020 for three types of c-Si materials, and emissions from shipping of these panels to the U.S. are also included. Figure 1b, d, and f showcase the emissions from U.S. domestic production of PV panels from 2020 to 2050 in five-year increments. Compared with relying on global supplies (offshore case) in 2020, domestic manufacturing of c-Si PV modules in the U.S. reduces GHG emissions by 23% and energy use by 4%. The offshore case in 2020 mainly relied on supplies from Malaysia (38%), Vietnam (21%), Thailand (17%), South Korea (9%), China (6%), and Singapore (3%)36,37. Manufacturing PV panels in Malaysia under the 2020 offshore case generates 42% more GHG emissions than manufacturing in the U.S., mainly due to the high emissions (26%-29% of all emissions) from solar grade silicon manufacturing stage for all three types of c-Si technologies (Fig. 1a, c, e), and the sc-Si crystal production stage that generates 26% to 28% of all emissions for sc-Si technology (Fig. 1a).
Fig. 1: Greenhouse gas emissions of crystalline silicon photovoltaic (PV) panel supplies to the U.S., with the breakdown of climate change impacts of each individual manufacturing stage and transportation.Results are presented for (a) single-crystalline silicon (sc-Si) PV in offshore cases, (b) sc-Si PV in reshored scenarios, (c) ribbon silicon (r-Si) in offshore cases, (d) r-Si in reshored scenarios, (e) multi-crystalline silicon (mc-Si) in offshore cases, as well as (f) mc-Si in reshored scenarios. Reshored manufacturing scenarios in (b, d, and f) illustrate the downward climate change impact trend over time, whereas offshore manufacturing cases in (a, c, and e) do not guarantee climate change mitigation over time, as illustrated by the higher emissions in 2015 than in 2010 in some regions. To study the impact of reshoring in 2020, we compare the 2020 case and the 2020 scenario. The sources of PV supplies in the 2020 case include China, South Korea, Malaysia, Singapore, Thailand, and Vietnam, as shown in (a, c, and e). The PV panels in the 2020 scenario are only manufactured in the U.S., as shown in (b, d, and f). We see a reduction of 23% global warming potential from PV panel manufacturing on average as a result of reshoring.
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Although the Malaysian government launched its Green Technology Policy in July 2009 to encourage and promote the use of renewable energy for Malaysia’s sustainable development38, almost half of its power generation still relied on coal (46%) a decade later after the policy was launched39. On the other hand, the U.S. relied heavily on natural gas (39%), which contributes almost twice as much to total electricity generation as coal source (20%)39. Besides the quartz mining stage, all stages require the use of electricity, as shown in Fig. 2. Among them, more high-voltage electricity power is needed in solar grade silicon manufacturing stage, which is on average six to ten times the amounts needed for electronics grade silicon and metallurgical grade silicon production. The power sector is one of the major sources of GHG emissions. The differences in power mixes between countries lead to discrepancies in climate change impacts of silicon manufacturing, which directly results in the gap in GHG emissions between the outsourced case and domestic scenario in 2020.
Fig. 2: Crystalline silicon photovoltaic panel manufacturing stages.The output from quartz mining stage is the silica sand, which is the input for the metallurgical grade silicon production (step 1). Metallurgical grade silicon is the input of both solar grade silicon production and electronics grade silicon production (step 2). Three types of crystalline silicon materials go through different paths for wafer production (step 3a & 4a for single-crystalline silicon, step 3b & 4b for multi-crystalline silicon, and step 3c for ribbon silicon). Photovoltaic cells are made from wafers (step 5), and photovoltaic panels are made from cells (step 6).
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Similarly, the energy performance of offshore cases (Fig. 3a, c, e) and reshored scenarios (Fig. 3b, d, f) are presented. Figure 3a, c, and e, similar with Fig. 1a, c, and e, exhibit the sources of PV supplies in cases from 2010 to 2020 across the entire supply chain for each trading partner (China, Malaysia, Japan, etc.), while Fig. 3b, d, and f showcase the scenarios in which production occurs in the U.S. itself. We see a 4% reduction in energy consumption when switching from offshore to reshored manufacturing in the same year, despite the decline in energy use being less significant than that of climate change mitigation. As opposed to the climate change impacts of reshored manufacturing in the U.S., which always results in lower GHG emissions than all offshore suppliers (30% lower than China, 17% lower than South Korea, 3% lower than Singapore, 18% lower than Thailand, as shown in Fig. 1), the energy consumption in the U.S. in the reshored scenario is not always lower than all suppliers in the offshore case in 2020, as shown in Fig. 3. Specifically, manufacturing c-Si PV in the U.S. requires more energy use than some of the suppliers in the outsourced case, such as Singapore (2% lower than the U.S.), Thailand (1% lower than the U.S.), and Vietnam (5% lower than the U.S.) (Fig. 3).
Fig. 3: Cumulative energy demand of crystalline silicon photovoltaic (PV) panel supplies to the U.S., with the breakdown of climate change impacts of each individual manufacturing stage and transportation.Results are presented for (a) single-crystalline silicon (sc-Si) PV in offshore cases, (b) sc-Si PV in reshored scenarios, (c) ribbon silicon (r-Si) in offshore cases, (d) r-Si in reshored scenarios, (e) multi-crystalline silicon (mc-Si) in offshore cases, as well as (f) mc-Si in reshored scenarios. Reshored manufacturing scenarios in (b, d, and f) illustrate the downward energy consumption trend over time, whereas offshore manufacturing cases in (a, c, and e) show that energy consumption can be higher when supplies change, as illustrated by the higher energy use in 2015 of some suppliers than in 2010. To study the impact of reshoring in 2020, we compare the 2020 case and the 2020 scenario. The sources of PV supplies in the 2020 case include China, South Korea, Malaysia, Singapore, Thailand, and Vietnam, as shown in (a, c, and e). The PV panels in the 2020 scenario are only manufactured in the U.S., as shown in (b, d, and f). We see a reduction of 4% energy use from PV panel manufacturing on average as a result of reshoring.
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We explore the reasons behind the lower energy footprint of manufacturing PV panels in offshore cases. Vietnam relied heavily on hydropower (28%), which is a much more efficient way to generate electricity than coal and natural gas. Modern hydro turbines can convert as much as 90% of energy into electricity, whereas the best fossil fuel plants are only 50% efficient40. Thus, less energy is required to manufacture PV panels in Vietnam due to more efficient energy usage. Meanwhile, transportation accounts for just 1% of CED, a minimal amount compared to the manufacturing stages. After oceanic shipping (1% of CED) is included for supplies from Vietnam, the total energy usage is still 5% lower than reshored manufacturing in the U.S. Despite the similar energy performance of production in Thailand and Singapore which also relied heavily on natural gas, as well as the lower energy use of c-Si PV production in Vietnam, the offshore manufacturing case still results in 4% higher CED compared with the reshored scenario in the same year. As mentioned earlier, the U.S. only attributed 41% of its PV supplies from these three countries in 2020 (21% from Vietnam, 17% from Thailand, and 3% from Singapore);36 the weighted average energy use when the U.S. relied on foreign suppliers is still higher than domestic production. However, reshored manufacturing does not guarantee an absolute energy performance advantage compared to offshore manufacturing due to the proximity (4% variation) of energy consumptions under the reshored scenario and the weighted average outsourced case.
Meeting the increasing demand for green power worldwide, growing shares of renewable energy sources over time as well as switching from global sourcing to reshored manufacturing would lead to greater climate change mitigation from c-Si PV module production in the future. The growing shares of renewable energy sources will not be possible without the increasing demand and supply of c-Si PV panels. Renewable penetration and expansion of c-Si PV panel manufacturing facilitate each other to achieve climate benefits. The amount of GHG emissions generated from reshored c-Si PV module production in the U.S. in 2050 is anticipated to reduce by 33% compared to relying on foreign supply in 2020 and 30% lower in 2035 than in 2020 (Fig. 1). The forecasted significant climate change mitigation is fulfilled by both reshoring manufacturing back to the U.S. and the large renewable penetration to the power grid, which is anticipated to happen in the U.S. in the next few decades41. The usage of renewable energy, including wind, solar, geothermal, etc., contributes to a 470% to 520% greater fraction of energy in 2050 than in 2010, exemplifying the far-reaching impacts of penetration of renewables into the power mix on CED impact analysis8. Compared to 2020, the coal-sourced share of electricity generation in the U.S. is projected to decrease by 18% in 2030, 33% in 2040, and 43% in 2050, while the nuclear source share would decrease by 27% in 2030, 37% in 2040, and 44% in 20508, as shown in Supplementary Methods 2: Electricity mix. As the U.S. transitions to greener sources of electricity, it is projected to rely on wind nearly twice as much starting merely from 2024, compared to the 2020 level. Among the renewable fuels, solar power is anticipated to increase by eightfold from 132 billion kWh in 2020 to 1071 billion kWh forecasted in 20508 (Supplementary Fig. 11). GHG emissions decrease appreciably over time as a result of both reshoring and the progression to more renewable power generation sources as a result of reshoring.
Despite the climate change mitigation, our results also shed light on the significant energy performance improvements. Compared with relying on global supplies in 2020, we project that domestic manufacturing of c-Si PV modules in the U.S. in 2035 and 2050 requires 13% and 17% less CED (Fig. 3 and Fig. 4), including 32% less non-renewable fossil energy (Fig. 4), indicating a significant energy reduction trend resulting from supply transition. Based on the projections on the energy decarbonization transition that happens alongside reshoring, we see not only larger shares of renewables accounting for primary energy consumption but, resultantly, overall lower primary energy consumptions over the years for all c-Si technology, as shown in Fig. 4.
Fig. 4: Impact analyses of the energy consumption of photovoltaic panel supplies to the U.S.Three cases in 2010, 2015, and 2020 are presented based on three types of crystalline silicon photovoltaic technologies: (a) single-crystalline silicon, (b) ribbon silicon, (c) multi-crystalline silicon. a–c represent the energy use for production across the entire supply chain for each trading partner. Seven scenarios in 2020, 2025, 2030, 2035, 2040, 2045, and 2050 are presented altogether in (d), with * indicating future scenarios.
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The trade structure significantly changed over the past few years, leading to an increased GHG emission from 2010 to 2015 (Fig. 1). The U.S. mainly relied on PV supplies from Taiwan (41%), Malaysia (29%), China mainland (14%), Germany (6%), Japan (6%), and Mexico (2%) in 2010, and Malaysia (32%), China mainland (31%), Taiwan (7%), Japan (6%), and Mexico (5%) in 2015, as shown in Fig. 5. The supply share of the PV system in Taiwan drastically reduced from 41% to 7%, and that of China mainland went up from 14% to 31% from 2010 to 2015, while other regions’ shares changed over time but not to any extent that would drive significant impacts (Fig. 5).
Fig. 5: Supply chain structure of solar photovoltaic panels shipped to the U.S. in 2010, 2015, and 2020. The suppliers involved in the 2010, 2015, and 2020 outsourced cases are determined based on the market share data.The U.S. mainly imported solar photovoltaic products from Asian trading partners. The market shares of module supplies changed dramatically over the years due to geopolitical tensions, safeguard tariffs, policies, etc. The rest of the world (RoW) includes all other suppliers other than the top six suppliers.
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The GHG emissions from panel production of the 2015 outsourced case are estimated to be even higher than the 2010 outsourced case. Although the life cycle carbon footprint of PV systems in China decreases by 5% (20 kg CO2 equivalent per 1 m2 of PV module manufactured) in 2015 compared to 2010, the U.S. imported more panels from mainland China in 2015 (31%) than in 2010 (14%). The GHG emissions from PV panel production in mainland China in 2015 are lower than in mainland China in 2010, but are still higher than the other suppliers (Germany, Japan, Mexico, Malaysia, Taiwan) in 2010, as shown in Fig. 1a, c, e, leading to a higher weighted sum of emissions from trading partners in 2015 than in 2010. Therefore, offshore manufacturing does not guarantee decreasing GHG emissions over time. The fluctuating GWP over the years is highly relevant to the displacements in the importing supply share of c-Si PVs. A supply chain crisis can occur at anytime that threatens the growth of the solar energy and the PV industry or even leads to increased GHG emissions in c-Si PV manufacturing. To stabilize the supply and to attain consistent emission reduction, reshoring is an option to consider, and growing efforts of reshoring manufacturing have been demonstrated5.
Similarly, the energy consumption of manufacturing PV panels in 2015 in some countries is higher than in the 2010 outsourced case. For instance, South Korea was not a major source of PV supplies to the U.S. in 2010, but it became one of the top six suppliers in 2015. Manufacturing PV panels in South Korea in 2015 requires 5% more energy than the average 2010 case, while Malaysia and Vietnam in 2015 requires 2% to 10% more energy than most suppliers (China, Germany, Japan, Mexico) in 2010. This indicates that when manufacturing locations shift from China, Germany, Japan, and Mexico in 2010 to South Korea, Malaysia, and Vietnam in 2015, the energy usage increases, as shown in Fig. 3. Clearly, with the ever-evolving pace of imported freight, the future of worldwide module production and the PV supply chain is uncertain, just as it was so easily disrupted by the supply crisis due to the COVID-19 pandemic42. Since the U.S. economy has faced many supply bottlenecks that contribute to high inflation, a strategy that ensures domestic manufacturing in the U.S. is encouraged43. As the U.S. PV demand growth continues, there might be an opportunity for further domestic manufacturing expansion, particularly given the potential supply chain disruption11.
Together with the impacts from reshoring and renewable penetration, we incorporate other factors with temporal or geographical variations, such as module efficiency, performance ratio, solar irradiation, and grid efficiency, in our analysis to study the energy and environmental impacts of these factors considered. Based on the Parameters under “Methods”, we estimate the carbon emission factor and the energy payback time (EPBT) of outsourced cases and domestic scenarios. We see that while other factors are taken into consideration, as illustrated in Fig. 6, the estimations of these two metrics also differ drastically between cases that rely on foreign supply and scenarios that depend on domestic production. As it stands, reshoring PV panel manufacturing sees a drastic reduction of carbon emission factor of 31% in 2035 and 33% in 2050 and EPBT decline of 14% in 2035 and 17% in 2050, compared with the 2020 offshore case (Fig. 6). The reductions can chiefly be accredited to the switch to reshored manufacturing and the changing breakdown of energy sources in the U.S. If reshored manufacturing can be achieved in 2035, among 31% of the reduction in carbon emission factor, reshoring leads to 23% of emission factor decrease while renewable penetration to the power grid contributes to 8%. On the other hand, when it comes to reductions in EPBT, 4% of EPBT decline is attributed to reshoring, while the remaining 10% are the credits of renewable penetration. We see that the act of reshoring has a greater impact on carbon emission reduction. The renewable penetration anticipated in the U.S. has a more significant influence on EPBT, but the projections on renewable penetration, including the soaring solar energy, can only be implemented if the PV panel supply surge in the next few years. Therefore, renewable penetration and reshored manufacturing for increasing PV demand are not mutually exclusive but rather in the same boat. They work together to drop carbon emission factors and lower EPBT of manufacturing c-Si PV panels.
Fig. 6: Carbon emission factor/greenhouse gas emission factor and energy payback time of outsourced cases (2010, 2015, 2020) and reshored scenarios (2020, 2025, 2030, 2035, 2040, 2045, 2050).The switch to reshored manufacturing and increasing renewable penetration to the power grid work together to drop (a) carbon emission factor and lower (b) energy payback time (EPBT) of manufacturing c-Si PV panels. The presented results are normalized and vary based on the colors shown on the color bar. In particular, the red and pink colors represent high carbon emission factors and high EPBT, suggesting more energy and environmental burdens, while the blue and green colors represent low carbon emission factors and low EPBT, indicating lower burdens. The 2020 outsourced case is defined as the reference for normalization.
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Besides our main analysis, we also study how other factors can have an impact on the energy and climate change profiles. We perform sensitivity analysis of various parameters on CED, GWP, carbon emission factor, EPBT, and energy return on energy invested (EROI) estimations. We first explore whether choosing the top six suppliers to represent the trading partners would or would not lead to significant bias in the energy and climate change results. As an additional litmus test for the number of global PV manufacturing locations to represent offshore locations, to ensure that the six suppliers chosen to represent the global supply sourcing market are appropriate, we conducted a sensitivity analysis on the number of suppliers designated in the market share calculations. We perform a sensitivity analysis specifically for the 2015 offshore case since the global supply of c-Si PV to the U.S. is less distinctly dominated by the top six suppliers (85% of supplies come from the top six) in 2015, whereas it was well-dominated by the top six in 2010 (99% from top six) and 2020 (93% from top six), as shown in Fig. 5. To perform this sensitivity analysis that includes more spatial variation, we study and compare the energy and environmental impacts of the top nine suppliers. Alongside the top six locations, we include Germany (4.07%), Singapore (3.16%), and Vietnam (2.90%) as the top suppliers. The calculated energy profile represented by CED decreases by less than 1% (0.97% for sc-Si, 0.89% for r-Si, and 0.94% for mc-Si), while environmental impact represented by GWP decreases by less than 2.5% (2.44% for sc-Si, 2.32% for r-Si, and 2.31% for mc-Si), as shown in Fig. 7a. The results thereby affirm that designating just the top six exporters as the major market share components is a succinct yet sufficiently representative group by which to assess the c-Si PV supply chain and trade structure before 2020.
Fig. 7: Sensitivity analysis of various parameters on cumulative energy demand, global warming potential, carbon emission factor, energy payback time, and energy return on investment estimations.The sensitivity analysis includes: (a) manufacturing supply chain structure (number of representative trading partners) and wafer manufacturing parameters on cumulative energy demand (CED) and global warming potential (GWP), (b) solar irradiation, performance ratio, module efficiency, lifetime, and grid efficiency on energy payback time (EPBT), carbon emission factor, and energy return on investment (EROI).
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We also perform sensitivity analysis of key parameters involved in the wafer manufacturing stage on energy and climate change impact. As an example of such an analysis, we show how reduced wafer thickness and kerf losses for slurry-based sawing would create an impact on CED and GWP when the wafers were manufactured in China in 2020. We find that the decline of these two parameters leads to a lessened amount of casted silicon and Czochralski silicon ingots needed for wafer production, which further leads to decreasing wafer weight input for PV cell and module production44. As a result, such changes in wafer thickness and kerf loss would cut CED by 27% (sc-Si) and 24% (mc-Si) and GWP by 29% (sc-Si) and 26% (mc-Si), as shown in Fig. 7a. On the other hand, according to the PV report by the Fraunhofer Institute for Solar Energy Systems that summarized the wafer thickness of c-Si PV cell development over the years45, the wafer thickness changed by no more than 5% from 2015 to 2020. Thus, we aim to mainly study and emphasize energy structure transitions and PV supplies instead, and the analysis regarding wafer thickness and kerf losses are considered in this sensitivity analysis.
We further investigate how variations in solar irradiation, performance ratio, module efficiency, lifetime, and grid efficiency can influence EPBT, carbon emission factor, and EROI. If grid efficiency increases from 30 to 70%46,47, EPBT can increase by 133%, and EROI can decrease by 57%, as shown in Fig. 7b. We see that through technological advancements, module efficiency is also anticipated to go up as a result of panel design improvements6, and we see an up to 17% increase in EROI and up to 15% decrease in carbon emission factor and EPBT as a result of improved module efficiency. We also take into consideration the degradation rates of c-Si PV panels which are reflected in their decreasing module efficiencies48. The results show that panel degradation leads to a 12% reduction in EROI for sc-Si and a 17% decrease for mc-Si, as well as a 14% increase in carbon emission factor and EPBT for sc-Si and a 20% increase for mc-Si. Another technological advancement we consider is the performance ratio49, which can lead to an 11% decrease in carbon emission factor if it reaches 90% and a 14% increase if it drops to 70%. Furthermore, we study the impacts of geographical location on these metrics from various levels of solar irradiation47. Regions with low solar irradiation come with higher carbon emission factors and EPBT, as shown by the 70% increase compared to medium irradiation regions, while regions with high solar irradiation demonstrate 26% lower carbon emission factor and EBPT. If the lifetime of the c-Si PV panel decreases by five years, the carbon emission factor would thus go up by 20%. The sensitivity analysis of various parameters can help us understand how technological advancements and geographical locations that place alongside manufacturing in the U.S. can have an impact on the energy and climate change metrics.
Reshoring c-Si PV manufacturing plays an important role in mitigating climate change. This study investigates the long-term implications of the current trend toward building a resilient and reliable reshored PV manufacturing supply. Departing from foreign supplies and instead bringing manufacturing back home will provide the PV industry with an alternative to fall back on when disruptions resurface. Reshored PV panel manufacturing is not only a strategy to protect domestic industry from supply bottlenecks but also aligns with the ambitious climate policy by substantially reducing carbon emissions.
In this study, the offshore manufacturing cases from 2010 to 2020 are considered as the U.S. previously relied on major PV panel imports from Asia12. The reshored manufacturing scenario in 2020 is studied unilaterally to examine whether the “Make it in America” strategy alone can support the climate agenda to realize decarbonization goals when compared with the offshore manufacturing case in the same year. More reshored manufacturing scenarios in 2025, 2030, 2035, 2040, 2045, and 2050 are forecasted to study how the reshored strategy and the climate policy interact in the next few centuries, given the disruptive nature that global politics could have on the PV supply chain.
Reshoring manufacturing reduces climate change impact from PV panel production by 23%, leading to tremendous benefits for the climate. Manufacturing and trade policies, significant financial support and incentives, as well as strategic actions focused on the workforce, will facilitate the rebuilding and continued operation of PV panel manufacturing facilities11. As the U.S. PV demand growth continues in the future, there may be opportunities for future domestic manufacturing expansion. If the reshored manufacturing can be achieved in 2035, a 30% climate change mitigation from manufacturing c-Si PV panels is expected. If the reshored manufacturing can be realized in 2050, a 33% mitigation of the climate change impact from panel production is projected. These reductions matter not only in the manufacturing stage but also in the overall scheme of the PV panel life cycle. The manufacturing stage of the c-Si PV life cycle is where the majority of GHG emissions occur31. Compared to the manufacturing stage, the operations life cycle stage of the solar PV system generates modest GHG emissions that are close to zero, due to the relatively low operational and maintenance requirements of PV systems31. A 1 m2 PV panel emits 0.27 kg CO2 eq GHG and demands 48 MJ of energy at its use stage33,34. Similarly, the amount of GHG emissions generated from the end-of-life treatment stage is minimal. A 1 m2 PV panel emits 0.57 kg CO2 eq GHG and demands 74 MJ of energy at its end-of-life treatment stage33,34. Putting them in the overall context of PV panel lifetime emissions and energy impact, the GHG emissions from the use stage contribute to less than 0.20% of PV lifetime emissions, and those from the end-of-life management stage contribute to less than 0.41%, as shown in Supplementary Fig. 4 under Supplementary Discussion 1: Manufacturing vs operations and maintenance vs end-of-life treatment. The energy use from the use stage contributes to less than 2.0% of lifetime energy use, and that from the end-of-life management stage contributes to less than 3.0%. Since most carbon emissions occur in the upstream manufacturing process, and contributions of emissions from the use stage and the disposal stage are generally low, we conclude that the climate change mitigations from panel manufacturing as a result of reshoring are significant in the overall lifetime emissions.
Based on our quantitative analysis, reshoring aligns with the ambitious climate target. As solar is expected to make up 40% of U.S. power by 2035 and up to 70–80% by 2050, this can only be made possible by producing more PV panels11. Although there are various emerging PV technologies, no alternative PV technology can displace c-Si quickly enough to achieve power sector decarbonization by 203550. Developing the U.S. c-Si PV domestic supply could mitigate challenges related to production disruption, compete with demand from other industries or countries, and maintain a robust U.S. domestic solar manufacturing leadership51,52. The Inflation Reduction Act encourages U.S. supply chains to span clean technologies, including solar technology, to create opportunities for small businesses and invest in American workers and the PV industry53. The legislation offers specific tax incentives for businesses that manufacture solar products domestically, and includes important requirements around domestic sourcing, such as the use of domestic panels in solar projects, as well as around prevailing wages and apprenticeships to ensure that good-paying jobs are offered to boost American manufacturing and competitiveness20. Policymakers have also stepped-up attempts to restart the American PV industry to renew efforts to bring manufacturing back. Such proposals draw on the momentum of a growing domestic movement in support of a “Green New Deal”, which has promised decent manufacturing jobs as a result of investments in low-carbon technologies and increasingly justified climate policies54. As of now, some policies explicitly aim at reshoring, such as tariffs put in place by past administrations, are still in effect, and a broad investigation into gaps in domestic supply chains has also been launched54.
Offshore manufacturing in the past does not always align with the climate target. Apart from the reshored manufacturing scenarios in the future that are assumption driven and formulated based on reasonable predictions, we also examine the past outsourced cases that relied on global supplies to interpret the impacts behind the ever-changing supply chain and manufacturing locations, as well as the power mix of trading partners from 2010 to 2020. Manufacturing c-Si PV panels from outsourced locations result in more GHG emissions in 2015 than in 2010. Moreover, as manufacturing locations shift from China, Germany, Japan, and Mexico in 2010 to South Korea, Malaysia, and Vietnam in 2015, the energy usage from panel production increases by up to 10% as well. As global dynamics shift quickly and more and more emerging supply crises demand our attention, it is difficult to determine an outsourced procurement strategy that not only complies with the ambitious national climate policies but also assures that geopolitical tensions would have no influence on it. Supply disruptions and bottlenecks can occur at any time to threaten the growth of renewable solar power and the PV industry, and the changing manufacturing deployment on account of policies and demand can increase GHG emissions. To stabilize supply and attain consistent carbon emission reduction, switching to leading-edge domestic manufacturing is an option to consider. Doing so will enable the pursuit of strategic objectives, particularly those in the energy, climate, and national security domains.
Manufacturing c-Si PV panels is attractive to pursue domestically as reshored production demonstrates many more benefits. The domestic production of solar products also aids in building broader coalitions and offers possible spillover benefits for climate policy. Outsourcing production to other countries over time is not a sustainable business model55. Offshoring can potentially result in job losses, wage reduction, and disruption of business innovation and productivity, which leads to policymakers proposing anti-offshoring or reshoring bills and policies that provide tax incentives for domestic production56. A reshored manufacturing base in solar PV may provide benefits such as more direct local employment and a more resilient energy supply system. Foreign manufacturers may be risky, impractical, or undesirable partners for public funds, whereas establishing a strong link between public funding of research and development and the domestic private sector has been identified as crucial to achieving climate goals, both by lowering the risks of scale-up and by granting access to markets57. The reshoring decision and climate agendas harmonize to ramp up climate actions, as carbon emission factors and EPBT of c-Si PV reshored manufacturing in the future reduce dramatically. If reshored manufacturing can be achieved in 2035, among 31% of the reduction in carbon emission factor from panel production, reshoring leads to a 23% of emission factor decrease while renewable penetration to the power grid contributes to 8%. On the other hand, among 14% of EPBT reductions from panel manufacturing, 4% of EPBT declines are attributed to reshoring, while the remaining 10% are the credits of renewable penetration. Renewable penetration and reshoring work together to create enormous energy and climate benefits. Renewable penetration to the power grid can only be made possible through more c-Si PV solar panel manufacturing and can only be achieved as the solar panel industry expands. As the U.S. achieves its energy transition goal by 2035 and 2050, the reshored panel manufacturing will benefit from large shares of renewables in the power grid by then in return. Besides energy and environmental strengths, the import costs of c-Si manufacturing inputs add 11% to the total expenditure, while a build-up in the domestic PV supply chain from “cradle-to-site” would dramatically reduce the cost11. Despite the minimized cost, c-Si PV manufacturing materials are mostly benign and available in very large quantities and have demonstrated long-term durability11. Besides, along with reshored manufacturing and increasing renewable power sources, technological innovations and breakthroughs can help achieve lower carbon emission factors and EPBT (15% by module efficiency advancement, 11% by performance ratio improvement) from PV panel production by 2050. Apart from withstanding supply crisis, reshored manufacturing is appealing to implement due to the numerous advantages listed above, which can be harmonized with technological advancements and renewable penetration to the power grid, and the conclusion of this study has important implications for other regions or industries to secure a reliable supply base.
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