1932

Abstract

Uncontrolled bleeding is a major problem in trauma and emergency medicine. While materials for trauma applications would certainly find utility in traditional surgical settings, the unique environment of emergency medicine introduces additional design considerations, including the need for materials that are easily deployed in austere environments. Ideally, these materials would be available off the shelf, could be easily transported, and would be able to be stored at room temperature for some amount of time. Both natural and synthetic materials have been explored for the development of hemostatic materials. This review article provides an overview of classes of materials used for topical hemostats and newer developments in the area of injectable hemostats for use in emergency medicine.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-bioeng-012521-101942
2022-06-06
2024-06-23
Loading full text...

Full text loading...

/deliver/fulltext/bioeng/24/1/annurev-bioeng-012521-101942.html?itemId=/content/journals/10.1146/annurev-bioeng-012521-101942&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Kauvar DS, Lefering R, Wade CE 2006. Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J. Trauma Acute Care Surg. 60:6S3–11
    [Google Scholar]
  2. 2.
    Dickinson LE, Gerecht S. 2016. Engineered biopolymeric scaffolds for chronic wound healing. Front. Physiol. 7:341
    [Google Scholar]
  3. 3.
    Thiruvoth FM, Mohapatra DP, Kumar D, Chittoria SRK, Nandhagopal V. 2015. Current concepts in the physiology of adult wound healing. Plast. Aesthetic Res. 2:250–56
    [Google Scholar]
  4. 4.
    Ozgok Kangal MK, Regan JP. 2022. Wound Healing Treasure Island, FL: StatPearls Publishing https://www.ncbi.nlm.nih.gov/books/NBK535406/
    [Google Scholar]
  5. 5.
    Wallace HA, Basehore BM, Zito PM. 2022. Wound Healing Phases Treasure Island, FL: StatPearls Publishing https://www.ncbi.nlm.nih.gov/books/NBK470443/
    [Google Scholar]
  6. 6.
    Sen Gupta A. 2017. Bio-inspired nanomedicine strategies for artificial blood components. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 9:6e1464
    [Google Scholar]
  7. 7.
    Tompeck AJ, Gajdhar AUR, Dowling M, Johnson SB, Barie PS et al. 2020. A comprehensive review of topical hemostatic agents: the good, the bad, and the novel. J. Trauma Acute Care Surg. 88:1e1–21
    [Google Scholar]
  8. 8.
    Hu Z, Zhang D-Y, Lu S-T, Li P-W, Li S-D. 2018. Chitosan-based composite materials for prospective hemostatic applications. Mar. Drugs 16:8273
    [Google Scholar]
  9. 9.
    He Q, Gong K, Ao Q, Ma T, Yan Y et al. 2013. Positive charge of chitosan retards blood coagulation on chitosan films. J. Biomater. Appl. 27:81032–45
    [Google Scholar]
  10. 10.
    Nainggolan I, Nasution TI, Putri SRE, Azdena D, Balyan M, Agusnar H. 2018. Study on chitosan film properties as a green dielectric. IOP Conf. Ser. Mater. Sci. Eng. 309:012081
    [Google Scholar]
  11. 11.
    Kunio NR, Riha GM, Watson KM, Differding JA, Schreiber MA, Watters JM. 2013. Chitosan based advanced hemostatic dressing is associated with decreased blood loss in a swine uncontrolled hemorrhage model. Am. J. Surg. 205:5505–10
    [Google Scholar]
  12. 12.
    Wang X, Zheng C, Wu Z, Teng D, Zhang X et al. 2009. Chitosan-NAC nanoparticles as a vehicle for nasal absorption enhancement of insulin. J. Biomed. Mater. Res. B Appl. Biomater. 88B:1150–61
    [Google Scholar]
  13. 13.
    Huang Y, Feng L, Zhang Y, He L, Wang C et al. 2017. Hemostasis mechanism and applications of N-alkylated chitosan sponge. Polym. Adv. Technol. 28:91107–14
    [Google Scholar]
  14. 14.
    Hattori H, Amano Y, Nogami Y, Takase B, Ishihara M 2010. Hemostasis for severe hemorrhage with photocrosslinkable chitosan hydrogel and calcium alginate. Ann. Biomed. Eng. 38:123724–32
    [Google Scholar]
  15. 15.
    Leonhardt EE, Kang N, Hamad MA, Wooley KL, Elsabahy M. 2019. Absorbable hemostatic hydrogels comprising composites of sacrificial templates and honeycomb-like nanofibrous mats of chitosan. Nat. Commun. 10:12307
    [Google Scholar]
  16. 16.
    Zhong YT, Hu HY, Min NN, Wei YF, Li XD, Li XR 2021. Application and outlook of topical hemostatic materials: a narrative review. Ann. Transl. Med. 9:7577
    [Google Scholar]
  17. 17.
    Yuan H, Chen L, Hong FF 2020. A biodegradable antibacterial nanocomposite based on oxidized bacterial nanocellulose for rapid hemostasis and wound healing. ACS Appl. Mater. Interfaces 12:33382–92
    [Google Scholar]
  18. 18.
    Udangawa RN, Mikael PE, Mancinelli C, Chapman C, Willard CF et al. 2019. Novel cellulose-halloysite hemostatic nanocomposite fibers with a dramatic reduction in human plasma coagulation time. ACS Appl. Mater. Interfaces 11:1715447–56
    [Google Scholar]
  19. 19.
    Kattula S, Byrnes JR, Wolberg AS. 2017. Fibrinogen and fibrin in hemostasis and thrombosis. Arterioscler. Thromb. Vasc. Biol. 37:3e13–21
    [Google Scholar]
  20. 20.
    Brown AC, Barker TH. 2014. Fibrin-based biomaterials: modulation of macroscopic properties through rational design at the molecular level. Acta Biomater. 10:41502–14
    [Google Scholar]
  21. 21.
    Quinn JV. 2005. Tissue Adhesives in Clinical Medicine Hamilton, Ontario, Canada: PMPH-USA. , 2nd ed..
    [Google Scholar]
  22. 22.
    Chiara O, Cimbanassi S, Bellanova G, Chiarugi M, Mingoli A et al. 2018. A systematic review on the use of topical hemostats in trauma and emergency surgery. BMC Surg. 18:168
    [Google Scholar]
  23. 23.
    US Food Drug Admin 2019. EVARREST (fibrin sealant patch). Regul. Doc. US Food Drug Admin. Silver Spring, MD: https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/evarrest-fibrin-sealant-patch
    [Google Scholar]
  24. 24.
    Li Z, Milionis A, Zheng Y, Yee M, Codispoti L et al. 2019. Superhydrophobic hemostatic nanofiber composites for fast clotting and minimal adhesion. Nat. Commun. 10:15562
    [Google Scholar]
  25. 25.
    Spotnitz WD. 2014. Fibrin sealant patches: powerful and easy-to-use hemostats. Open Access Surg. 7:71–79
    [Google Scholar]
  26. 26.
    Chandrashekar A, Singh G, Garry J, Sikalas N, Labropoulos N. 2018. Mechanical and biochemical role of fibrin within a venous thrombus. Eur. J. Vasc. Endovasc. Surg. 55:3417–24
    [Google Scholar]
  27. 27.
    Fakhari A, Berkland C. 2013. Applications and emerging trends of hyaluronic acid in tissue engineering, as a dermal filler, and in osteoarthritis treatment. Acta Biomater. 9:77081–92
    [Google Scholar]
  28. 28.
    Luo J-W, Liu C, Wu J-H, Zhao D-H, Lin L-X et al. 2020. In situ forming gelatin/hyaluronic acid hydrogel for tissue sealing and hemostasis. J. Biomed. Mater. Res. B Appl. Biomater. 108:3790–97
    [Google Scholar]
  29. 29.
    Wang D, Xu P, Wang S, Li W, Liu W 2020. Rapidly curable hyaluronic acid-catechol hydrogels inspired by scallops as tissue adhesives for hemostasis and wound healing. Eur. Polym. J. 134:109763
    [Google Scholar]
  30. 30.
    Lewis KM, Kuntze CE, Gulle H. 2015. Control of bleeding in surgical procedures: critical appraisal of HEMOPATCH (sealing hemostat). Med. Devices 9:1–10
    [Google Scholar]
  31. 31.
    Lewis KM, Spazierer D, Slezak P, Baumgartner B, Regenbogen J, Gulle H 2014. Swelling, sealing, and hemostatic ability of a novel biomaterial: a polyethylene glycol-coated collagen pad. J. Biomater. Appl. 29:5780–88
    [Google Scholar]
  32. 32.
    Wei W, Liu J, Peng Z, Liang M, Wang Y, Wang X 2020. Gellable silk fibroin-polyethylene sponge for hemostasis. Artif. Cells Nanomed. Biotechnol. 48:128–36
    [Google Scholar]
  33. 33.
    Bu Y, Zhang L, Sun G, Sun F, Liu J et al. 2019. Tetra-PEG based hydrogel sealants for in vivo visceral hemostasis. Adv. Mater. 31:281901580
    [Google Scholar]
  34. 34.
    Daristotle JL, Zaki ST, Lau LW, Torres L, Zografos A et al. 2019. Improving the adhesion, flexibility, and hemostatic efficacy of a sprayable polymer blend surgical sealant by incorporating silica particles. Acta Biomater. 90:205–16
    [Google Scholar]
  35. 35.
    Xu L-C, Bauer J, Siedlecki CA. 2014. Proteins, platelets, and blood coagulation at biomaterial interfaces. Colloids Surf. B Biointerfaces 124:49–68
    [Google Scholar]
  36. 36.
    Lubich C, Allacher P, de la Rosa M, Bauer A, Prenninger T et al. 2016. The mystery of antibodies against polyethylene glycol (PEG)—what do we know?. Pharm. Res. 33:92239–49
    [Google Scholar]
  37. 37.
    Ganson NJ, Povsic TJ, Sullenger BA, Alexander JH, Zelenkofske SL et al. 2016. Pre-existing anti-polyethylene glycol antibody linked to first-exposure allergic reactions to pegnivacogin, a PEGylated RNA aptamer. J. Allergy Clin. Immunol. 137:51610–13.e7
    [Google Scholar]
  38. 38.
    Park S, Han U, Choi D, Hong J. 2018. Layer-by-layer assembled polymeric thin films as prospective drug delivery carriers: design and applications. Biomater. Res. 22:129
    [Google Scholar]
  39. 39.
    Alkekhia D, Hammond PT, Shukla A. 2020. Layer-by-layer biomaterials for drug delivery. Annu. Rev. Biomed. Eng. 22:1–24
    [Google Scholar]
  40. 40.
    Shukla A, Almeida B. 2014. Advances in cellular and tissue engineering using layer-by-layer assembly. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 6:5411–21
    [Google Scholar]
  41. 41.
    Decher G, Hong JD. 1991. Buildup of ultrathin multilayer films by a self-assembly process: II. Consecutive adsorption of anionic and cationic bipolar amphiphiles and polyelectrolytes on charged surfaces. Berichte Bunsenges. Phys. Chem. 95:111430–34
    [Google Scholar]
  42. 42.
    Decher G, Hong JD. 1991. Buildup of ultrathin multilayer films by a self-assembly process, 1: Consecutive adsorption of anionic and cationic bipolar amphiphiles on charged surfaces. Makromol. Chem. Macromol. Symp. 46:1321–27
    [Google Scholar]
  43. 43.
    Decher G. 1997. Fuzzy nanoassemblies: toward layered polymeric multicomposites. Science 277:53301232–37
    [Google Scholar]
  44. 44.
    Alkekhia D, Shukla A 2019. Influence of poly-l-lysine molecular weight on antibacterial efficacy in polymer multilayer films. J. Biomed. Mater. Res. A 107:61324–39
    [Google Scholar]
  45. 45.
    Zhuk I, Jariwala F, Attygalle AB, Wu Y, Libera MR, Sukhishvili SA. 2014. Self-defensive layer-by-layer films with bacteria-triggered antibiotic release. ACS Nano 8:87733–45
    [Google Scholar]
  46. 46.
    Shukla A, Fang JC, Puranam S, Hammond PT 2012. Release of vancomycin from multilayer coated absorbent gelatin sponges. J. Control. Release 157:164–71
    [Google Scholar]
  47. 47.
    Shukla A, Avadhany SN, Fang JC, Hammond PT. 2010. Tunable vancomycin releasing surfaces for biomedical applications. Small Weinh. Bergstr. Ger. 6:212392–404
    [Google Scholar]
  48. 48.
    Shukla A, Fuller RC, Hammond PT. 2011. Design of multi-drug release coatings targeting infection and inflammation. J. Control. Release 155:2159–66
    [Google Scholar]
  49. 49.
    Choi KY, Correa S, Min J, Li J, Roy S et al. 2019. Binary targeting of siRNA to hematologic cancer cells in vivo using layer-by-layer nanoparticles. Adv. Funct. Mater. 29:201900018
    [Google Scholar]
  50. 50.
    Wang S, Battigelli A, Alkekhia D, Fairman A, Antoci V et al. 2020. Controlled delivery of a protein tyrosine phosphatase inhibitor, SHP099, using cyclodextrin-mediated host-guest interactions in polyelectrolyte multilayer films for cancer therapy. RSC Adv. 10:3420073–82
    [Google Scholar]
  51. 51.
    Deng ZJ, Morton SW, Ben-Akiva E, Dreaden EC, Shopsowitz KE, Hammond PT. 2013. Layer-by-layer nanoparticles for systemic codelivery of an anticancer drug and siRNA for potential triple-negative breast cancer treatment. ACS Nano 7:119571–84
    [Google Scholar]
  52. 52.
    Kapadia CH, Ioele SA, Day ES. 2020. Layer-by-layer assembled PLGA nanoparticles carrying miR-34a cargo inhibit the proliferation and cell cycle progression of triple-negative breast cancer cells. J. Biomed. Mater. Res. A 108:3601–13
    [Google Scholar]
  53. 53.
    Zeng J, Matsusaki M. 2019. Layer-by-layer assembly of nanofilms to control cell functions. Polym. Chem. 10:232960–74
    [Google Scholar]
  54. 54.
    Shah NJ, Hyder MN, Quadir MA, Courchesne N-MD, Seeherman HJ et al. 2014. Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction. PNAS 111:3512847–52
    [Google Scholar]
  55. 55.
    Zhang S, Xing M, Li B 2018. Biomimetic layer-by-layer self-assembly of nanofilms, nanocoatings, and 3D scaffolds for tissue engineering. Int. J. Mol. Sci. 19:61641
    [Google Scholar]
  56. 56.
    Kharlampieva E, Kozlovskaya V, Chan J, Ankner JF, Tsukruk VV 2009. Spin-assisted layer-by-layer assembly: variation of stratification as studied with neutron reflectivity. Langmuir 25:2414017–24
    [Google Scholar]
  57. 57.
    Krogman KC, Lowery JL, Zacharia NS, Rutledge GC, Hammond PT. 2009. Spraying asymmetry into functional membranes layer-by-layer. Nat. Mater. 8:6512–18
    [Google Scholar]
  58. 58.
    Castleberry SA, Li W, Deng D, Mayner S, Hammond PT 2014. Capillary flow layer-by-layer: a microfluidic platform for the high-throughput assembly and screening of nanolayered film libraries. ACS Nano 8:76580–89
    [Google Scholar]
  59. 59.
    Shukla A, Fang JC, Puranam S, Jensen FR, Hammond PT. 2012. Hemostatic multilayer coatings. Adv. Mater. 24:4492–96
    [Google Scholar]
  60. 60.
    Huang X, Jia J, Wang Z, Hu Q 2015. A novel chitosan-based sponge coated with self-assembled thrombin/tannic acid multilayer films as a hemostatic dressing. Chin. J. Polym. Sci. 33:2284–90
    [Google Scholar]
  61. 61.
    Guillot R, Gilde F, Becquart P, Sailhan F, Lapeyrere A et al. 2013. The stability of BMP loaded polyelectrolyte multilayer coatings on titanium. Biomaterials 34:235737–46
    [Google Scholar]
  62. 62.
    Shukla A, Puranam S, Hammond PT 2012. Vancomycin storage stability in multilayer thin film coatings for on-demand care. J. Biomater. Sci. Polym. Ed. 23:151895–902
    [Google Scholar]
  63. 63.
    Hsu BB, Conway W, Tschabrunn CM, Mehta M, Perez-Cuevas MB et al. 2015. Clotting mimicry from robust hemostatic bandages based on self-assembling peptides. ACS Nano 9:99394–406
    [Google Scholar]
  64. 64.
    Komachi T, Sumiyoshi H, Inagaki Y, Takeoka S, Nagase Y, Okamura Y. 2017. Adhesive and robust multilayered poly(lactic acid) nanosheets for hemostatic dressing in liver injury model. J. Biomed. Mater. Res. B Appl. Biomater. 105:71747–57
    [Google Scholar]
  65. 65.
    Hsu BB, Hagerman SR, Jamieson K, Castleberry SA, Wang W et al. 2015. Multifunctional self-assembled films for rapid hemostat and sustained anti-infective delivery. ACS Biomater. Sci. Eng. 1:3148–56
    [Google Scholar]
  66. 66.
    Tan L, Zhou X, Wu K, Yang D, Jiao Y, Zhou C 2020. Tannic acid/CaII anchored on the surface of chitin nanofiber sponge by layer-by-layer deposition: integrating effective antibacterial and hemostatic performance. Int. J. Biol. Macromol. 159:304–15
    [Google Scholar]
  67. 67.
    Che C, Liu L, Wang X, Zhang X, Luan S et al. 2020. Surface-adaptive and on-demand antibacterial sponge for synergistic rapid hemostasis and wound disinfection. ACS Biomater. Sci. Eng. 6:31776–86
    [Google Scholar]
  68. 68.
    Zheng W, Chen C, Zhang X, Wen X, Xiao Y et al. 2021. Layer-by-layer coating of carboxymethyl chitosan-gelatin-alginate on cotton gauze for hemostasis and wound healing. Surf. Coat. Technol. 406:126644
    [Google Scholar]
  69. 69.
    Liu J-Y, Hu Y, Li L, Wang C, Wang J et al. 2020. Biomass-derived multilayer-structured microparticles for accelerated hemostasis and bone repair. Adv. Sci. 7:222002243
    [Google Scholar]
  70. 70.
    Zhang L, Sun J, Zhou Y, Zhong Y, Ying Y et al. 2017. Layer-by-layer assembly of Cu3(BTC)2 on chitosan non-woven fabrics: a promising haemostatic decontaminant composite material against sulfur mustard. J. Mater. Chem. B 5:306138–46
    [Google Scholar]
  71. 71.
    Chan LW-G, Wang X, Wei H, Pozzo LD, White NJ, Pun SH. 2015. A synthetic fibrin-crosslinking polymer for modulating clot properties and inducing hemostasis. Sci. Transl. Med. 7:277277ra29
    [Google Scholar]
  72. 72.
    Nandi S, Brown AC. 2016. Platelet-mimetic strategies for modulating the wound environment and inflammatory responses. Exp. Biol. Med. 241:101138–48
    [Google Scholar]
  73. 73.
    Anselmo AC, Modery-Pawlowski CL, Menegatti S, Kumar S, Vogus DR et al. 2014. Platelet-like nanoparticles: mimicking shape, flexibility, and surface biology of platelets to target vascular injuries. ACS Nano 8:1111243–53
    [Google Scholar]
  74. 74.
    Dyer MR, Hickman D, Luc N, Haldeman S, Loughran P et al. 2018. Intravenous administration of synthetic platelets (SynthoPlate) in a mouse liver injury model of uncontrolled hemorrhage improves hemostasis. J. Trauma Acute Care Surg. 84:6917–23
    [Google Scholar]
  75. 75.
    Girish A, Sekhon U, Sen Gupta A. 2020. Bioinspired artificial platelets for transfusion applications in traumatic hemorrhage. Transfusion 60:2229–31
    [Google Scholar]
  76. 76.
    Hickman DA, Pawlowski CL, Shevitz A, Luc NF, Kim A et al. 2018. Intravenous synthetic platelet (SynthoPlate) nanoconstructs reduce bleeding and improve ‘golden hour’ survival in a porcine model of traumatic arterial hemorrhage. Sci. Rep. 8:3118
    [Google Scholar]
  77. 77.
    Nandi S, Sproul EP, Nellenbach K, Erb M, Gaffney L et al. 2019. Platelet-like particles dynamically stiffen fibrin matrices and improve wound healing outcomes. Biomater. Sci. 7:2669–82
    [Google Scholar]
  78. 78.
    Nandi S, Sommerville L, Nellenbach K, Mihalko E, Erb M et al. 2020. Platelet-like particles improve fibrin network properties in a hemophilic model of provisional matrix structural defects. J. Colloid Interface Sci. 577:406–18
    [Google Scholar]
  79. 79.
    Brown AC, Stabenfeldt SE, Ahn B, Hannan RT, Dhada KS et al. 2014. Ultrasoft microgels displaying emergent platelet-like behaviours. Nat. Mater. 13:121108–14
    [Google Scholar]
  80. 80.
    Chee E, Nandi S, Nellenbach K, Mihalko E, Snider DB et al. 2020. Nanosilver composite pNIPAm microgels for the development of antimicrobial platelet-like particles. J. Biomed. Mater. Res. B Appl. Biomater. 108:62599–609
    [Google Scholar]
  81. 81.
    Hubbard WB, Lashof-Sullivan MM, Lavik EB, VandeVord PJ. 2015. Steroid-loaded hemostatic nanoparticles combat lung injury after blast trauma. ACS Macro Lett. 4:4387–91
    [Google Scholar]
  82. 82.
    Hubbard WB, Lashof-Sullivan M, Greenberg S, Norris C, Eck J et al. 2018. Hemostatic nanoparticles increase survival, mitigate neuropathology and alleviate anxiety in a rodent blast trauma model. Sci. Rep. 8:10622
    [Google Scholar]
  83. 83.
    Onwukwe C, Maisha N, Holland M, Varley M, Groynom R et al. 2018. Engineering intravenously administered nanoparticles to reduce infusion reaction and stop bleeding in a large animal model of trauma. Bioconjug. Chem. 29:72436–47
    [Google Scholar]
  84. 84.
    Peng HT. 2020. Hemostatic agents for prehospital hemorrhage control: a narrative review. Mil. Med. Res. 7:113
    [Google Scholar]
  85. 85.
    Gao Y, Sarode A, Kokoroskos N, Ukidve A, Zhao Z et al. 2020. A polymer-based systemic hemostatic agent. Sci. Adv. 6:31eaba0588
    [Google Scholar]
  86. 86.
    Lokhande G, Carrow JK, Thakur T, Xavier JR, Parani M et al. 2018. Nanoengineered injectable hydrogels for wound healing application. Acta Biomater. 70:35–47
    [Google Scholar]
  87. 87.
    Gaharwar AK, Avery RK, Assmann A, Paul A, McKinley GH et al. 2014. Shear-thinning nanocomposite hydrogels for the treatment of hemorrhage. ACS Nano 8:109833–42
    [Google Scholar]
  88. 88.
    Gkikas M, Peponis T, Mesar T, Hong C, Avery RK et al. 2019. Systemically administered hemostatic nanoparticles for identification and treatment of internal bleeding. ACS Biomater. Sci. Eng. 5:52563–76
    [Google Scholar]
  89. 89.
    Baylis JR, Chan KYT, Kastrup CJ 2016. Halting hemorrhage with self-propelling particles and local drug delivery. Thromb. Res. 141:S36–39
    [Google Scholar]
  90. 90.
    Baylis JR, Finkelstein-Kulka A, Macias-Valle L, Manji J, Lee M et al. 2017. Rapid hemostasis in a sheep model using particles that propel thrombin and tranexamic acid. Laryngoscope 127:4787–93
    [Google Scholar]
  91. 91.
    Sproul EP, Nandi S, Chee E, Sivadanam S, Igo BJ et al. 2020. Development of biomimetic antimicrobial platelet-like particles comprised of microgel nanogold composites. Regen. Eng. Transl. Med. 6:299–309
    [Google Scholar]
  92. 92.
    Zhu J, Li F, Wang X, Yu J, Wu D 2018. Hyaluronic acid and polyethylene glycol hybrid hydrogel encapsulating nanogel with hemostasis and sustainable antibacterial property for wound healing. ACS Appl. Mater. Interfaces 10:1613304–16
    [Google Scholar]
/content/journals/10.1146/annurev-bioeng-012521-101942
Loading
/content/journals/10.1146/annurev-bioeng-012521-101942
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error