Nanobiotech engineering for future coral reefs

Abstract

Advances in bioengineering and nanotechnology are revolutionizing how we approach problems deemed unsolvable only a decade ago. Nanotechnology has transformed biomedicine, agriculture, and energy science, with broad translational capacity to natural systems. Coral reef ecosystems provide immense biodiversity and economic value but are being degraded at an unprecedented rate, triggering calls for human interventions such as those that have been applied to biomedical systems. Here, we propose that next-generation nanobiotechnology (nanocarriers, nanobiosensors, 3D bioprinting) can be leveraged to provide solutions for the persistence of future reefs. We advocate initiating critical dialogues and developing translational tools to apply to coral reef ecosystems. We challenge and invite the scientific community and industry to harness and expand the available bioengineering and nanotechnology toolkits for applied monitoring, rehabilitation, restoration, and conservation of coral reefs worldwide. Advances in bioengineering and nanotechnology are revolutionizing how we approach problems deemed unsolvable only a decade ago. Nanotechnology has transformed biomedicine, agriculture, and energy science, with broad translational capacity to natural systems. Coral reef ecosystems provide immense biodiversity and economic value but are being degraded at an unprecedented rate, triggering calls for human interventions such as those that have been applied to biomedical systems. Here, we propose that next-generation nanobiotechnology (nanocarriers, nanobiosensors, 3D bioprinting) can be leveraged to provide solutions for the persistence of future reefs. We advocate initiating critical dialogues and developing translational tools to apply to coral reef ecosystems. We challenge and invite the scientific community and industry to harness and expand the available bioengineering and nanotechnology toolkits for applied monitoring, rehabilitation, restoration, and conservation of coral reefs worldwide. Reef-building corals are colonial cnidarian animals that partner with unicellular endosymbiotic dinoflagellate algae of the family Symbiodiniaceae and a highly heterogeneous suite of bacteria, archaea, viruses, and fungi, collectively known as the coral holobiont. In this nutritional symbiosis, the endosymbiotic algae can supply the daily metabolic carbon demands of the coral host,1McCloskey L. Muscatine L. Production and respiration in the Red Sea coral Stylophora pistillata as a function of depth.Proc. Roy. Soc. Lond. B Biol. Sci. 1984; 222: 215-230Crossref Scopus (123) Google Scholar which, combined with heterotrophic feeding, fuels coral growth and reef accretion essential to the formation of the 3D structure characteristic of coral reefs. Increasing ocean temperatures and marine heat waves are threatening the persistence of coral reef ecosystems.2Hughes T.P. Kerry J.T. Simpson T. Large-scale bleaching of corals on the great barrier reef.Ecology. 2018; 99: 501https://doi.org/10.1002/ecy.2092Crossref PubMed Scopus (91) Google Scholar Thermal stress can disrupt cnidarian-algal symbiosis,3Venn A.A. Loram J.E. Douglas A.E. Photosynthetic symbioses in animals.J. Exp. Bot. 2008; 59: 1069-1080https://doi.org/10.1093/jxb/erm328Crossref PubMed Scopus (266) Google Scholar culminating in the massive loss of endosymbiotic dinoflagellates; this dysbiosis is known as coral bleaching. Although projections about the rate of coral loss are continuously being adjusted, the unanimous consensus is that climate change is causing the rapid disappearance of tropical coral reefs and threatening their extinction within this century.4IPCCPörtner H.-O. Roberts D.C. Tignor M. Poloczanska E.S. Mintenbeck K. Alegría A. Craig M. Langsdorf S. Löschke S. Möller V. Climate Change 2022: Impacts, Adaptation, and Vulnerability. Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change. Cambridge University Press, 2022Google Scholar Combined with ocean acidification, coral disease, eutrophication, and overfishing, these global and local stressors have led to a substantial decline in successful coral recruitment,5Hughes T.P. Kerry J.T. Baird A.H. Connolly S.R. Chase T.J. Dietzel A. Hill T. Hoey A.S. Hoogenboom M.O. 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The repercussions of coral reef degradation are far reaching and include the loss of food security and coastal protection, as well as tourism and trade; these major ecosystem goods and services are estimated to amount to over $30 billion USD annually.9Santavy D.L. Horstmann C.L. Sharpe L.M. Yee S.H. Ringold P. What is it about coral reefs? Translation of ecosystem goods and services relevant to people and their well-being.Ecosphere. 2021; 12: 1-27Crossref PubMed Scopus (4) Google Scholar,10Spalding M. Burke L. Wood S.A. Ashpole J. Hutchison J. Zu Ermgassen P. Mapping the global value and distribution of coral reef tourism.Mar. Pol. 2017; 82: 104-113Crossref Scopus (0) Google Scholar Beyond governmental agreements and carbon dioxide emission caps, human interventions have included responses such as the creation of marine protected areas,11Kelleher G. Kenchington R.A. Guidelines for Establishing Marine Protected Areas. Iucn, 1991Google Scholar,12Maestro M. Pérez-Cayeiro M.L. 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USA. 2015; 112: 2307-2313https://doi.org/10.1073/pnas.1422301112Crossref PubMed Scopus (524) Google Scholar,16National Academies of Sciences, Engineering, and MedicineA Research Review of Interventions to Increase the Persistence and Resilience of Coral Reefs.2018Google Scholar and therapeutic treatments including the engineering of antibiotic materials and probiotics.17Anthony K. Bay L.K. Costanza R. Firn J. Gunn J. Harrison P. Heyward A. Lundgren P. Mead D. Moore T. et al.New interventions are needed to save coral reefs.Nat. Ecol. Evol. 2017; 1: 1420-1422Crossref PubMed Scopus (144) Google Scholar,18Peixoto R.S. Rosado P.M. de Assis Leite D.C. Rosado A.S. Bourne D.G. Beneficial microorganisms for corals (BMC): proposed mechanisms for coral health and resilience.Front. Microbiol. 2017; 8: 341Crossref PubMed Scopus (259) Google Scholar We believe that the development of such transformative human interventions on coral reefs could substantially benefit from exploiting breakthrough technologies from adjacent engineering fields, specifically nanotechnology (Box 1) and 3D biofabrication (Box 2) (collectively referred to as nanobiotechnology). Here, we outline how next-generation nanobiotechnology could revolutionize coral reef research and provide solutions for future coral reefs.Box 1NanotechnologyNanotechnology is the science, engineering, and technology that measure and manipulate materials (e.g., CNTs, carbon nanotubes; TiO2, titanium dioxide) in the range of 1–100 nm (10−9 m) compared with common biological units (e.g., human egg, frog egg, DNA, H2O water molecule). At this scale, the surface area-to-volume (SA/V) ratios of nanoparticles (NPs) are orders of magnitude larger than their bulk equivalents, which confers significantly enhanced catalytic capacity, sensitivity to stimuli, and other unique physical, optical, electronic, and magnetic properties. The benefits of nanotechnology are readily evident in medicine, which has been permanently changed by nanobased optical probes, radiation and chemical sensors, cell actuators, drug carriers, catalysts, and surface modifiers. Nanosensors can detect analytes that serve as biomarkers for organismal health and transduce signals in real time via optical, electronic, and physical outputs.19Chauhan V.M. Orsi G. Brown A. Pritchard D.I. Aylott J.W. Mapping the pharyngeal and intestinal pH of Caenorhabditis elegans and real-time luminal pH oscillations using extended dynamic range pH-sensitive nanosensors.ACS Nano. 2013; 7: 5577-5587https://doi.org/10.1021/nn401856uCrossref PubMed Scopus (77) Google Scholar Sensitivity and versatility of nanosensors are rapidly improving, and state-of-the-art nanosensors can specifically detect single molecules, enabling sensing of living cells, organisms, and their associated environments.20Rong G. Tuttle E.E. Neal Reilly A. Clark H.A. Recent developments in nanosensors for imaging applications in biological systems.Annu. Rev. Anal. Chem. 2019; 12: 109-128Crossref PubMed Scopus (24) Google Scholar,21Sharma P. Pandey V. Sharma M.M.M. Patra A. Singh B. Mehta S. Husen A. A review on biosensors and nanosensors application in agroecosystems.Nanoscale Res. Lett. 2021; 16: 136https://doi.org/10.1186/s11671-021-03593-0Crossref PubMed Scopus (54) Google Scholar Nanosensors are being packaged in wearable devices and textiles, which streamlines sensing of environmental temperature, salinity, and drought/dehydration with real-time automated responses in the field.22Kim J. Campbell A.S. de Ávila B.E.F. Wang J. Wearable biosensors for healthcare monitoring.Nat. Biotechnol. 2019; 37: 389-406Crossref PubMed Scopus (1400) Google Scholar Additionally, NP surface engineering can be used to specifically target plant pathogens,23Abd-Elsalam K.A. Prasad R. Nanobiotechnology Applications in Plant Protection. Springer, 2018Crossref Google Scholar thus promoting plant growth and stress tolerance.24Zhao L. Lu L. Wang A. Zhang H. Huang M. Wu H. Xing B. Wang Z. Ji R. Nano-biotechnology in agriculture: use of nanomaterials to promote plant growth and stress tolerance.J. Agric. Food Chem. 2020; 68: 1935-1947https://doi.org/10.1021/acs.jafc.9b06615Crossref PubMed Scopus (228) Google ScholarSince NPs are 103–106 times smaller than eukaryotic cells, they possess high intrinsic rates of cell penetration. Once inside a cell, the NPs can degrade, transform, and react with biological molecules, potentially inducing toxicities. Strategies to minimize toxicity while maintaining performance include designing biomimetic NPs based on cell membranes, extracellular vesicles, viruses, and other biological structures (reviewed in Chen et al.25Chen L. Hong W. Ren W. Xu T. Qian Z. He Z. Recent progress in targeted delivery vectors based on biomimetic nanoparticles.Signal Transduct. Target. Ther. 2021; 6 (225-25)Google Scholar).Box 23D biofabricationView Large Image Figure ViewerDownload Hi-res image Download (PPT)The growing need for personalized medicine is constantly driving research efforts toward on-demand organ fabrication.26Truby R.L. Lewis J.A. Printing soft matter in three dimensions.Nature. 2016; 540: 371-378https://doi.org/10.1038/nature21003Crossref PubMed Scopus (932) Google Scholar,27Yu C. Schimelman J. Wang P. Miller K.L. Ma X. You S. Guan J. Sun B. Zhu W. Chen S. Photopolymerizable biomaterials and light-based 3D printing strategies for biomedical applications.Chem. Rev. 2020; 120: 10695-10743https://doi.org/10.1021/acs.chemrev.9b00810Crossref PubMed Scopus (180) Google Scholar 3D bioprinting allows for controlled 3D organization of living cells to form tissue- and organ-mimicking scaffolds.28Grigoryan B. Paulsen S.J. Corbett D.C. Sazer D.W. Fortin C.L. Zaita A.J. Greenfield P.T. Calafat N.J. Gounley J.P. Ta A.H. et al.Multivascular networks and functional intravascular topologies within biocompatible hydrogels.Science. 2019; 364: 458-464Crossref PubMed Scopus (705) Google Scholar It has revolutionized regenerative medicine, drug screening and delivery, and disease monitoring.26Truby R.L. Lewis J.A. Printing soft matter in three dimensions.Nature. 2016; 540: 371-378https://doi.org/10.1038/nature21003Crossref PubMed Scopus (932) Google Scholar Major breakthroughs include the biofabrication of heart muscles,29Lee A. Hudson A.R. Shiwarski D.J. Tashman J.W. Hinton T.J. Yerneni S. Bliley J.M. Campbell P.G. Feinberg A.W. 3D bioprinting of collagen to rebuild components of the human heart.Science. 2019; 365: 482-487https://doi.org/10.1126/science.aav9051Crossref PubMed Scopus (832) Google Scholar synthetic liver,30Ma X. Qu X. Zhu W. Li Y.S. Yuan S. Zhang H. Liu J. Wang P. Lai C.S.E. Zanella F. et al.Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting.Proc. Natl. Acad. Sci. USA. 2016; 113: 2206-2211https://doi.org/10.1073/pnas.1524510113Crossref PubMed Scopus (578) Google Scholar and multifunctional living materials for bioremediation, bioenergy,31Wangpraseurt D. You S. Azam F. Jacucci G. Gaidarenko O. Hildebrand M. Kühl M. Smith A.G. Davey M.P. Smith A. et al.Bionic 3D printed corals.Nat. Commun. 2020; 11: 1748https://doi.org/10.1038/s41467-020-15486-4Crossref PubMed Scopus (47) Google Scholar and living devices (“organ on a chip”).32Wangpraseurt D. You S. Sun Y. Chen S. Biomimetic 3D living materials powered by microorganisms.Trends Biotechnol. 2022; 40: 843-857https://doi.org/10.1016/j.tibtech.2022.01.003Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Beyond issues of printability, the grand challenge of bioprinting is the addition of essential nutrients and the removal of waste products from the system.Current bioprinting techniques can be broadly categorized into material-deposition-based 3D printing and light-assisted 3D printing. Inkjet and extrusion 3D printing deposit materials in a drop-by-drop or line-by-line manner, respectively. Once deposited, the material must polymerize quickly to counteract shear stress and support the growing 3D structure. Light-assisted 3D printing uses a prepolymer that is crosslinked during light exposure. Crosslinking or photopolymerization is induced when light interacts with a light-sensitive photoinitiator compound that polymerizes a covalently crosslinked hydrogel.27Yu C. Schimelman J. Wang P. Miller K.L. Ma X. You S. Guan J. Sun B. Zhu W. Chen S. Photopolymerizable biomaterials and light-based 3D printing strategies for biomedical applications.Chem. Rev. 2020; 120: 10695-10743https://doi.org/10.1021/acs.chemrev.9b00810Crossref PubMed Scopus (180) Google Scholar Because light can be precisely manipulated via focusing optics, light-assisted techniques have high spatial resolution. Stereolithography uses a laser beam to selectively polymerize in a point scanning fashion. Digital light processing (DLP)-based printing uses patterned light to rapidly polymerize an area. The technique is based on a digital micromirror device (DMD) that controls millions of micromirrors that each correspond to a pixel of the digital mask that is printed. Printing is performed in a layer-by-layer manner, facilitating the printing of large-scale areas rapidly. In contrast, two-photon polymerization can achieve the highest spatial resolution (submicrometer) but is comparatively slow. Nanotechnology is the science, engineering, and technology that measure and manipulate materials (e.g., CNTs, carbon nanotubes; TiO2, titanium dioxide) in the range of 1–100 nm (10−9 m) compared with common biological units (e.g., human egg, frog egg, DNA, H2O water molecule). At this scale, the surface area-to-volume (SA/V) ratios of nanoparticles (NPs) are orders of magnitude larger than their bulk equivalents, which confers significantly enhanced catalytic capacity, sensitivity to stimuli, and other unique physical, optical, electronic, and magnetic properties. The benefits of nanotechnology are readily evident in medicine, which has been permanently changed by nanobased optical probes, radiation and chemical sensors, cell actuators, drug carriers, catalysts, and surface modifiers. Nanosensors can detect analytes that serve as biomarkers for organismal health and transduce signals in real time via optical, electronic, and physical outputs.19Chauhan V.M. Orsi G. Brown A. Pritchard D.I. Aylott J.W. Mapping the pharyngeal and intestinal pH of Caenorhabditis elegans and real-time luminal pH oscillations using extended dynamic range pH-sensitive nanosensors.ACS Nano. 2013; 7: 5577-5587https://doi.org/10.1021/nn401856uCrossref PubMed Scopus (77) Google Scholar Sensitivity and versatility of nanosensors are rapidly improving, and state-of-the-art nanosensors can specifically detect single molecules, enabling sensing of living cells, organisms, and their associated environments.20Rong G. Tuttle E.E. Neal Reilly A. Clark H.A. Recent developments in nanosensors for imaging applications in biological systems.Annu. Rev. Anal. Chem. 2019; 12: 109-128Crossref PubMed Scopus (24) Google Scholar,21Sharma P. Pandey V. Sharma M.M.M. Patra A. Singh B. Mehta S. Husen A. A review on biosensors and nanosensors application in agroecosystems.Nanoscale Res. Lett. 2021; 16: 136https://doi.org/10.1186/s11671-021-03593-0Crossref PubMed Scopus (54) Google Scholar Nanosensors are being packaged in wearable devices and textiles, which streamlines sensing of environmental temperature, salinity, and drought/dehydration with real-time automated responses in the field.22Kim J. Campbell A.S. de Ávila B.E.F. Wang J. Wearable biosensors for healthcare monitoring.Nat. Biotechnol. 2019; 37: 389-406Crossref PubMed Scopus (1400) Google Scholar Additionally, NP surface engineering can be used to specifically target plant pathogens,23Abd-Elsalam K.A. Prasad R. Nanobiotechnology Applications in Plant Protection. Springer, 2018Crossref Google Scholar thus promoting plant growth and stress tolerance.24Zhao L. Lu L. Wang A. Zhang H. Huang M. Wu H. Xing B. Wang Z. Ji R. Nano-biotechnology in agriculture: use of nanomaterials to promote plant growth and stress tolerance.J. Agric. Food Chem. 2020; 68: 1935-1947https://doi.org/10.1021/acs.jafc.9b06615Crossref PubMed Scopus (228) Google Scholar Since NPs are 103–106 times smaller than eukaryotic cells, they possess high intrinsic rates of cell penetration. Once inside a cell, the NPs can degrade, transform, and react with biological molecules, potentially inducing toxicities. Strategies to minimize toxicity while maintaining performance include designing biomimetic NPs based on cell membranes, extracellular vesicles, viruses, and other biological structures (reviewed in Chen et al.25Chen L. Hong W. Ren W. Xu T. Qian Z. He Z. Recent progress in targeted delivery vectors based on biomimetic nanoparticles.Signal Transduct. Target. Ther. 2021; 6 (225-25)Google Scholar). The growing need for personalized medicine is constantly driving research efforts toward on-demand organ fabrication.26Truby R.L. Lewis J.A. Printing soft matter in three dimensions.Nature. 2016; 540: 371-378https://doi.org/10.1038/nature21003Crossref PubMed Scopus (932) Google Scholar,27Yu C. Schimelman J. Wang P. Miller K.L. Ma X. You S. Guan J. Sun B. Zhu W. Chen S. Photopolymerizable biomaterials and light-based 3D printing strategies for biomedical applications.Chem. Rev. 2020; 120: 10695-10743https://doi.org/10.1021/acs.chemrev.9b00810Crossref PubMed Scopus (180) Google Scholar 3D bioprinting allows for controlled 3D organization of living cells to form tissue- and organ-mimicking scaffolds.28Grigoryan B. Paulsen S.J. Corbett D.C. Sazer D.W. Fortin C.L. Zaita A.J. Greenfield P.T. Calafat N.J. Gounley J.P. Ta A.H. et al.Multivascular networks and functional intravascular topologies within biocompatible hydrogels.Science. 2019; 364: 458-464Crossref PubMed Scopus (705) Google Scholar It has revolutionized regenerative medicine, drug screening and delivery, and disease monitoring.26Truby R.L. Lewis J.A. Printing soft matter in three dimensions.Nature. 2016; 540: 371-378https://doi.org/10.1038/nature21003Crossref PubMed Scopus (932) Google Scholar Major breakthroughs include the biofabrication of heart muscles,29Lee A. Hudson A.R. Shiwarski D.J. Tashman J.W. Hinton T.J. Yerneni S. Bliley J.M. Campbell P.G. Feinberg A.W. 3D bioprinting of collagen to rebuild components of the human heart.Science. 2019; 365: 482-487https://doi.org/10.1126/science.aav9051Crossref PubMed Scopus (832) Google Scholar synthetic liver,30Ma X. Qu X. Zhu W. Li Y.S. Yuan S. Zhang H. Liu J. Wang P. Lai C.S.E. Zanella F. et al.Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting.Proc. Natl. Acad. Sci. USA. 2016; 113: 2206-2211https://doi.org/10.1073/pnas.1524510113Crossref PubMed Scopus (578) Google Scholar and multifunctional living materials for bioremediation, bioenergy,31Wangpraseurt D. You S. Azam F. Jacucci G. Gaidarenko O. Hildebrand M. Kühl M. Smith A.G. Davey M.P. Smith A. et al.Bionic 3D printed corals.Nat. Commun. 2020; 11: 1748https://doi.org/10.1038/s41467-020-15486-4Crossref PubMed Scopus (47) Google Scholar and living devices (“organ on a chip”).32Wangpraseurt D. You S. Sun Y. Chen S. Biomimetic 3D living materials powered by microorganisms.Trends Biotechnol. 2022; 40: 843-857https://doi.org/10.1016/j.tibtech.2022.01.003Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Beyond issues of printability, the grand challenge of bioprinting is the addition of essential nutrients and the removal of waste products from the system. Current bioprinting techniques can be broadly categorized into material-deposition-based 3D printing and light-assisted 3D printing. Inkjet and extrusion 3D printing deposit materials in a drop-by-drop or line-by-line manner, respectively. Once deposited, the material must polymerize quickly to counteract shear stress and support the growing 3D structure. Light-assisted 3D printing uses a prepolymer that is crosslinked during light exposure. Crosslinking or photopolymerization is induced when light interacts with a light-sensitive photoinitiator compound that polymerizes a covalently crosslinked hydrogel.27Yu C. Schimelman J. Wang P. Miller K.L. Ma X. You S. Guan J. Sun B. Zhu W. Chen S. Photopolymerizable biomaterials and light-based 3D printing strategies for biomedical applications.Chem. Rev. 2020; 120: 10695-10743https://doi.org/10.1021/acs.chemrev.9b00810Crossref PubMed Scopus (180) Google Scholar Because light can be precisely manipulated via focusing optics, light-assisted techniques have high spatial resolution. Stereolithography uses a laser beam to selectively polymerize in a point scanning fashion. Digital light processing (DLP)-based printing uses patterned light to rapidly polymerize an area. The technique is based on a digital micromirror device (DMD) that controls millions of micromirrors that each correspond to a pixel of the digital mask that is printed. Printing is performed in a layer-by-layer manner, facilitating the printing of large-scale areas rapidly. In contrast, two-photon polymerization can achieve the highest spatial resolution (submicrometer) but is comparatively slow. 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