Development of 3D-bioprinted artificial blood vessels loaded with rapamycin-nanoparticles for ischemic repair
Vascular diseases, including ischemic conditions and restenosis, pose significant challenges in clinical practice. Restenosis, the re-narrowing of blood vessels after interventions such as stent placement, remains a major concern despite advances in medical interventions. Addressing these challenges requires innovative approaches that promote vascular regeneration and prevent restenosis. By leveraging the capabilities of three-dimensional (3D) printing technology, artificial blood vessels with lumen can be precisely constructed in customizable sizes, closely mimicking the natural vascular architecture. This approach allows for the incorporation of therapeutic agents and cells to enhance the functionality of the fabricated vessels. In the present study, we investigated the fabrication and characterization of artificial blood vessels using 3D printing technology, with the focus on achieving precise control over the vessel dimensions and architecture to ensure optimal functionality. The use of 3D printing enabled the creation of patient-specific blood vessels with tailored sizes and geometries, providing a personalized solution for vascular treatment. Furthermore, we explored the integration of nanoparticles loaded with therapeutic drugs within the 3D-printed blood vessels. Specifically, rapamycin, a potent drug for preventing restenosis, was encapsulated within the nanoparticles to enable controlled drug release. This approach aimed to address the challenge of restenosis by delivering the drug directly to the affected site and maintaining its therapeutic concentration over an extended period. Additionally, the study investigated the incorporation of endothelial progenitor cells (EPCs), which promote re-endothelialization essential for vascular regeneration and long-term vessel functionality, within the artificial blood vessels. The 3D-printed blood vessels provide an ideal environment for the integration and growth of these cells, further enhancing their regenerative potential. By combining 3D printing technology, drug-loaded nanoparticles, and EPCs, this study demonstrated the potential of this approach in fabricating functional artificial blood vessels.
- Pittman RN, 2011, Regulation of tissue oxygenation, in Integrated Systems Physiology: From Molecule to Function to Disease, San Rafael, CA.
- Tang QR, Xue H, Zhang Q, et al., 2021, Evaluation of the clinical efficacy of stem cell transplantation in the treatment of spinal cord injury: A systematic review and meta-analysis. Cell Transplant, 30:9636897211067804. doi: 10.1177/09636897211067804
- Mao AS, Mooney DJ, 2015, Regenerative medicine: Current therapies and future directions. Proc Natl Acad Sci U S A, 112(47):14452-14459. doi: 10.1073/pnas.1508520112
- Zakrzewski W, Dobrzynski M, Szymonowicz M, et al., 2019, Stem cells: Past, present, and future. Stem Cell Res Ther, 10(1):68. doi: 10.1186/s13287-019-1165-5
- Dzobo K, Thomford NE, Senthebane DA, et al., 2018, Advances in regenerative medicine and tissue engineering: innovation and transformation of medicine. Stem Cells Int, 2018:2495848. doi: 10.1155/2018/2495848
- Serbo JV, Gerecht S, 2013, Vascular tissue engineering: Biodegradable scaffold platforms to promote angiogenesis. Stem Cell Res Ther, 4(1):8. doi: 10.1186/scrt156
- Kwon SG, Kwon YW, Lee TW, et al., 2018, Recent advances in stem cell therapeutics and tissue engineering strategies. Biomater Res, 22:36. doi: 10.1186/s40824-018-0148-4
- Song HG, Rumma RT, Ozaki CK, et al., 2018, Vascular tissue engineering: Progress, challenges, and clinical promise. Cell Stem Cell, 22(3):340-354. doi: 10.1016/j.stem.2018.02.009
- Wakabayashi T, Naito H, 2023, Cellular heterogeneity and stem cells of vascular endothelial cells in blood vessel formation and homeostasis: Insights from single-cell RNA sequencing. Front Cell Dev Biol, 11:1146399. doi: 10.3389/fcell.2023.1146399
- Carmeliet P, Jain RK, 2011, Molecular mechanisms and clinical applications of angiogenesis. Nature, 473(7347):298-307. doi: 10.1038/nature10144
- Majewska A, Wilkus K, Brodaczewska K, et al., 2021, Endothelial cells as tools to model tissue microenvironment in hypoxia-dependent pathologies. Int J Mol Sci, 22(2). doi: 10.3390/ijms22020520
- Phelps EA, Garcia AJ, 2010, Engineering more than a cell: Vascularization strategies in tissue engineering. Curr Opin Biotechnol, 21(5):704-709. doi: 10.1016/j.copbio.2010.06.005
- Munisso MC, Yamaoka T, 2020, Circulating endothelial progenitor cells in small-diameter artificial blood vessel. J Artif Organs, 23(1):6-13. doi: 10.1007/s10047-019-01114-6
- Chambers SEJ, Pathak V, Pedrini E, et al., 2021, Current concepts on endothelial stem cells definition, location, and markers. Stem Cells Transl Med, 10(Suppl 2):S54-S61. doi: 10.1002/sctm.21-0022
- Yoder MC, 2012, Human endothelial progenitor cells. Cold Spring Harb Perspect Med, 2(7):a006692. doi: 10.1101/cshperspect.a006692
- Peters EB, 2018, Endothelial progenitor cells for the vascularization of engineered tissues. Tissue Eng Part B Rev, 24(1):1-24. doi: 10.1089/ten.TEB.2017.0127
- Zhang F, King MW, 2022, Immunomodulation strategies for the successful regeneration of a tissue-engineered vascular graft. Adv Healthc Mater, 11(12):e2200045. doi: 10.1002/adhm.202200045
- Wang D, Xu Y, Li Q, et al., 2020, Artificial small-diameter blood vessels: Materials, fabrication, surface modification, mechanical properties, and bioactive functionalities. J Mater Chem B, 8(9):1801-1822. doi: 10.1039/c9tb01849b
- Hu K, Li Y, Ke Z, et al., 2022, History, progress and future challenges of artificial blood vessels: A narrative review. Biomater Transl, 3(1):81-98. doi: 10.12336/biomatertransl.2022.01.008
- Ozbolat IT, Hospodiuk M, 2016, Current advances and future perspectives in extrusion-based bioprinting. Biomaterials, 76:321-343. doi: 10.1016/j.biomaterials.2015.10.076
- Fu Z, Naghieh S, Xu C, et al., 2021, Printability in extrusion bioprinting. Biofabrication, 13(3). doi: 10.1088/1758-5090/abe7ab
- Yang GH, Kang D, An S, et al., 2022, Advances in the development of tubular structures using extrusion-based 3D cell-printing technology for vascular tissue regenerative applications. Biomater Res, 26(1):73. doi: 10.1186/s40824-022-00321-2
- Angelopoulos I, Allenby MC, Lim M, et al., 2020, Engineering inkjet bioprinting processes toward translational therapies. Biotechnol Bioeng, 117(1):272-284. doi: 10.1002/bit.27176
- Li X, Liu B, Pei B, et al., 2020, Inkjet bioprinting of biomaterials. Chem Rev, 120(19):10793-10833. doi: 10.1021/acs.chemrev.0c00008
- Suntornnond R, Ng WL, Huang X, et al., 2022, Improving printability of hydrogel-based bio-inks for thermal inkjet bioprinting applications via saponification and heat treatment processes. J Mater Chem B, 10(31): 5989-6000. doi: 10.1039/d2tb00442a
- Li W, Mille LS, Robledo JA, et al., 2020, Recent advances in formulating and processing biomaterial inks for vat polymerization-based 3D printing. Adv Healthc Mater, 9(15):e2000156. doi: 10.1002/adhm.202000156
- Yu C, Schimelman J, Wang P, et al., 2020, Photopolymerizable biomaterials and light-based 3D printing strategies for biomedical applications. Chem Rev, 120(19): 10695-10743. doi: 10.1021/acs.chemrev.9b00810
- Xu X, Awad A, Robles-Martinez P, et al., 2021, Vat photopolymerization 3D printing for advanced drug delivery and medical device applications. J Control Release, 329:743-757. doi: 10.1016/j.jconrel.2020.10.008
- Ali A, Saeed S, Hussain R, et al., 2023, Synthesis and characterization of silica, silver-silica, and zinc oxide-silica nanoparticles for evaluation of blood biochemistry, oxidative stress, and hepatotoxicity in albino rats. Acs Omega, 8(23):20900-20911. doi: 10.1021/acsomega.3c01674
- Chen S, Greasley SL, Ong ZY, et al., 2020, Biodegradable zinc-containing mesoporous silica nanoparticles for cancer therapy. Mater Today Adv, 6:100066. doi: 10.1016/j.mtadv.2020.100066
- Waksman R, Ajani AE, Pichard AD, et al., 2004, Oral rapamycin to inhibit restenosis after stenting of de novo coronary lesions: The Oral rapamune to inhibit restenosis (ORBIT) study. J Am Coll Cardiol, 44(7):1386-1392. doi: 10.1016/j.jacc.2004.06.069
- Rosner D, McCarthy N, Bennett M, 2005, Rapamycin inhibits human in stent restenosis vascular smooth muscle cells independently of pRB phosphorylation and p53. Cardiovasc Res, 66(3):601-610. doi: 10.1016/j.cardiores.2005.01.006
- Voisard R, Zellmann S, Muller F, et al., 2007, Sirolimus inhibits key events of restenosis in vitro/ex vivo: Evaluation of the clinical relevance of the data by SI/MPL- and SI/DES-ratios. BMC Cardiovasc Disord, 7:15. doi: 10.1186/1471-2261-7-15
- Brara PS, Moussavian M, Grise MA, et al., 2003, Pilot trial of oral rapamycin for recalcitrant restenosis. Circulation, 107(13):1722-1724. doi: 10.1161/01.CIR.0000066282.05411.17
- Kim J, Kim HS, Lee N, et al., 2008, Multifunctional uniform nanoparticles composed of a magnetite nanocrystal core and a mesoporous silica shell for magnetic resonance and fluorescence imaging and for drug delivery. Angew Chem Int Ed Engl, 47(44):8438-8441. doi: 10.1002/anie.200802469
- Zhou Q, Doherty J, Akk A, et al., 2022, Safety profile of rapamycin perfluorocarbon nanoparticles for preventing cisplatin-induced kidney injury. Nanomaterials (Basel), 12(3). doi: 10.3390/nano12030336
- Earla R, Cholkar K, Gunda S, et al., 2012, Bioanalytical method validation of rapamycin in ocular matrix by QTRAP LC-MS/ MS: Application to rabbit anterior tissue distribution by topical administration of rapamycin nanomicellar formulation. J Chromatogr B Analyt Technol Biomed Life Sci, 908:76-86. doi: 10.1016/j.jchromb.2012.09.014
- Lee JH, Lee SH, Choi SH, et al., 2015, The sulfated polysaccharide fucoidan rescues senescence of endothelial colony-forming cells for ischemic repair. Stem Cells, 33(6):1939-1951. doi: 10.1002/stem.1973
- Bonaca MP, Hamburg NM, Creager MA, 2021, Contemporary medical management of peripheral artery disease. Circ Res, 128(12):1868-1884. doi: 10.1161/CIRCRESAHA.121.318258
- Gul F, Janzer SF, 2023, Peripheral Vascular Disease, StatPearls, Treasure Island (FL).
- Chin K, 2011, In-stent restenosis: The gold standard has changed. EuroIntervention, 7(Suppl K):K43-K46. doi: 10.4244/EIJV7SKA7
- Rao J, Pan Bei H, Yang Y, et al., 2020, Nitric oxide-producing cardiovascular stent coatings for prevention of thrombosis and restenosis. Front Bioeng Biotechnol, 8:578. doi: 10.3389/fbioe.2020.00578
- Perkins LE, 2010, Preclinical models of restenosis and their application in the evaluation of drug-eluting stent systems. Vet Pathol, 47(1):58-76. doi: 10.1177/0300985809352978
- Nowicki M, Castro NJ, Rao R, et al., 2017, Integrating three-dimensional printing and nanotechnology for musculoskeletal regeneration. Nanotechnology,28(38):382001. doi: 10.1088/1361-6528/aa8351
- Fischetti T, Borciani G, Avnet S, et al., 2023, Incorporation/ enrichment of 3D bioprinted constructs by biomimetic nanoparticles: Tuning printability and cell behavior in bone models. Nanomaterials (Basel), 13(14). doi: 10.3390/nano13142040
- Johannesson J, Pathare MM, Johansson M, et al., 2023, Synergistic stabilization of emulsion gel by nanoparticles and surfactant enables 3D printing of lipid-rich solid oral dosage forms. J Colloid Interface Sci, 650(Pt B):1253-1264. doi: 10.1016/j.jcis.2023.07.055
- Remaggi G, Bergamonti L, Graiff C, et al., 2023, Rapid prototyping of 3D-printed AgNPs- and nano-TiO(2)-embedded hydrogels as novel devices with multiresponsive antimicrobial capability in wound healing. Antibiotics (Basel), 12(7). doi: 10.3390/antibiotics12071104
- Liu Y, Li K, Liu B, et al., 2010, A strategy for precision engineering of nanoparticles of biodegradable copolymers for quantitative control of targeted drug delivery. Biomaterials, 31(35):9145-9155. doi: 10.1016/j.biomaterials.2010.08.053
- Tripathi D, Srivastava M, Rathour K, et al., 2023, A promising approach of dermal targeting of antipsoriatic drugs via engineered nanocarriers drug delivery systems for tackling psoriasis. Drug Metab Bioanal Lett. doi: 10.2174/2949681016666230803150329
- Mitchell MJ, Billingsley MM, Haley RM, et al., 2021, Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov, 20(2):101-124. doi: 10.1038/s41573-020-0090-8
- Kasravi M, Ahmadi A, Babajani A, et al., 2023, Immunogenicity of decellularized extracellular matrix scaffolds: A bottleneck in tissue engineering and regenerative medicine. Biomater Res, 27(1):10. doi: 10.1186/s40824-023-00348-z
- Pinnock CB, Meier EM, Joshi NN, et al., 2016, Customizable engineered blood vessels using 3D printed inserts. Methods, 99:20-27. doi: 10.1016/j.ymeth.2015.12.015
- Kakisis JD, Liapis CD, Breuer C, et al., 2005, Artificial blood vessel: The Holy Grail of peripheral vascular surgery. J Vasc Surg, 41(2):349-354. doi: 10.1016/j.jvs.2004.12.026
- Marx SO, Totary-Jain H, Marks AR, 2011, Vascular smooth muscle cell proliferation in restenosis. Circ Cardiovasc Interv, 4(1):104-111. doi: 10.1161/CIRCINTERVENTIONS.110.957332
- Huang C, Zhao J, Zhu Y, 2020, Drug-eluting stent targeting Sp-1-attenuated restenosis by engaging YAP-mediated vascular smooth muscle cell phenotypic modulation. J Am Heart Assoc, 9(1):e014103. doi: 10.1161/JAHA.119.014103
- Huang C, Zhang W, Zhu Y, 2019, Drug-eluting stent specifically designed to target vascular smooth muscle cell phenotypic modulation attenuated restenosis through the YAP pathway. Am J Physiol Heart Circ Physiol, 317(3):H541-H551. doi: 10.1152/ajpheart.00089.2019
- Yetisgin AA, Cetinel S, Zuvin M, et al., 2020, Therapeutic nanoparticles and their targeted delivery applications. Molecules, 25(9). doi: 10.3390/molecules25092193
- Falke LL, van Vuuren SH, Kazazi-Hyseni F, et al., 2015, Local therapeutic efficacy with reduced systemic side effects by rapamycin-loaded subcapsular microspheres. Biomaterials, 42:151-160. doi: 10.1016/j.biomaterials.2014.11.042
- Cheng X, Xie Q, Sun Y, 2023, Advances in nanomaterial-based targeted drug delivery systems. Front Bioeng Biotechnol, 11:1177151. doi: 10.3389/fbioe.2023.1177151
- Chen EP, Toksoy Z, Davis BA, et al., 2021, 3D bioprinting of vascularized tissues for in vitro and in vivo applications. Front Bioeng Biotechnol, 9:664188. doi: 10.3389/fbioe.2021.664188
- Papaioannou TG, Manolesou D, Dimakakos E, et al., 2019, 3D bioprinting methods and techniques: Applications on artificial blood vessel fabrication. Acta Cardiol Sin, 35(3):284-289. doi: 10.6515/ACS.201905_35(3).20181115A
- Tajabadi M, Goran Orimi H, Ramzgouyan MR, et al., 2022, Regenerative strategies for the consequences of myocardial infarction: Chronological indication and upcoming visions. Biomed Pharmacother, 146:112584 doi: 10.1016/j.biopha.2021.112584
- Craparo EF, Cabibbo M, Conigliaro A, et al., 2021, Rapamycin-loaded polymeric nanoparticles as an advanced formulation for macrophage targeting in atherosclerosis. Pharmaceutics, 13(4). doi: 10.3390/pharmaceutics13040503
- Shi Y, Jiao C, Lu X, et al., 2022, Rapamycin nanoparticles improves drug bioavailability in PLAM treatment by interstitial injection. Orphanet J Rare Dis, 17(1):349. doi: 10.1186/s13023-022-02511-6
- Chen Y, Zeng Y, Zhu X, et al., 2021, Significant difference between sirolimus and paclitaxel nanoparticles in anti-proliferation effect in normoxia and hypoxia: The basis of better selection of atherosclerosis treatment. Bioact Mater, 6(3):880-889. doi: 10.1016/j.bioactmat.2020.09.005