A Tumor‐on‐a‐Chip System with Bioprinted Blood and Lymphatic Vessel Pair
Current in vitro antitumor drug screening strategies insufficiently mimic biological systems. They tend to lack true perfusion and draining microcirculation systems, which may post significant limitations in explicitly reproducing the transport kinetics of cancer therapeutics. Herein, the fabricatio...
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Published in | Advanced functional materials Vol. 29; no. 31 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
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Wiley Subscription Services, Inc
01.08.2019
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Abstract | Current in vitro antitumor drug screening strategies insufficiently mimic biological systems. They tend to lack true perfusion and draining microcirculation systems, which may post significant limitations in explicitly reproducing the transport kinetics of cancer therapeutics. Herein, the fabrication of an improved tumor model consisting of a bioprinted hollow blood vessel and a lymphatic vessel pair, hosted in a 3D tumor microenvironment‐mimetic hydrogel matrix is reported, termed as the tumor‐on‐a‐chip with a bioprinted blood and a lymphatic vessel pair (TOC‐BBL). The bioprinted blood vessel is a perfusable channel with an opening on both ends, while the bioprinted lymphatic vessel is blinded on one end, both of which are embedded in a hydrogel tumor mass, with vessel permeability individually tunable through optimization of the compositions of the bioinks. It is demonstrated that systems with different combinations of these bioprinted blood/lymphatic vessels exhibit varying levels of diffusion profiles for biomolecules and anticancer drugs. The results suggest that this unique in vitro tumor model containing the bioprinted blood/lymphatic vessel pair may have the capacity of simulating the complex transport mechanisms of certain pharmaceutical compounds inside the tumor microenvironment, potentially providing improved accuracy in future cancer drug screening.
A tumor model consisting of a bioprinted hollow blood vessel and a lymphatic vessel pair hosted in a 3D hydrogel matrix is fabricated, which may have the capacity to simulate the complex transport mechanisms of pharmaceutical compounds inside the tumor microenvironment, potentially providing improved accuracy in future cancer drug screening. |
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AbstractList | Current in vitro antitumor drug screening strategies insufficiently mimic biological systems. They tend to lack true perfusion and draining microcirculation systems, which may post significant limitations in explicitly reproducing the transport kinetics of cancer therapeutics. Herein, the fabrication of an improved tumor model consisting of a bioprinted hollow blood vessel and a lymphatic vessel pair, hosted in a 3D tumor microenvironment‐mimetic hydrogel matrix is reported, termed as the tumor‐on‐a‐chip with a bioprinted blood and a lymphatic vessel pair (TOC‐BBL). The bioprinted blood vessel is a perfusable channel with an opening on both ends, while the bioprinted lymphatic vessel is blinded on one end, both of which are embedded in a hydrogel tumor mass, with vessel permeability individually tunable through optimization of the compositions of the bioinks. It is demonstrated that systems with different combinations of these bioprinted blood/lymphatic vessels exhibit varying levels of diffusion profiles for biomolecules and anticancer drugs. The results suggest that this unique in vitro tumor model containing the bioprinted blood/lymphatic vessel pair may have the capacity of simulating the complex transport mechanisms of certain pharmaceutical compounds inside the tumor microenvironment, potentially providing improved accuracy in future cancer drug screening. Current in vitro antitumor drug screening strategies insufficiently mimic biological systems. They tend to lack true perfusion and draining microcirculation systems, which may post significant limitations in explicitly reproducing the transport kinetics of cancer therapeutics. Herein, the fabrication of an improved tumor model consisting of a bioprinted hollow blood vessel and a lymphatic vessel pair, hosted in a 3D tumor microenvironment‐mimetic hydrogel matrix is reported, termed as the tumor‐on‐a‐chip with a bioprinted blood and a lymphatic vessel pair (TOC‐BBL). The bioprinted blood vessel is a perfusable channel with an opening on both ends, while the bioprinted lymphatic vessel is blinded on one end, both of which are embedded in a hydrogel tumor mass, with vessel permeability individually tunable through optimization of the compositions of the bioinks. It is demonstrated that systems with different combinations of these bioprinted blood/lymphatic vessels exhibit varying levels of diffusion profiles for biomolecules and anticancer drugs. The results suggest that this unique in vitro tumor model containing the bioprinted blood/lymphatic vessel pair may have the capacity of simulating the complex transport mechanisms of certain pharmaceutical compounds inside the tumor microenvironment, potentially providing improved accuracy in future cancer drug screening. A tumor model consisting of a bioprinted hollow blood vessel and a lymphatic vessel pair hosted in a 3D hydrogel matrix is fabricated, which may have the capacity to simulate the complex transport mechanisms of pharmaceutical compounds inside the tumor microenvironment, potentially providing improved accuracy in future cancer drug screening. Current in vitro anti-tumor drug screening strategies are insufficiently portrayed lacking true perfusion and draining microcirculation systems, which may post significant limitation in reproducing the transport kinetics of cancer therapeutics explicitly. Herein, we report the fabrication of an improved tumor model consisting of bioprinted hollow blood vessel and lymphatic vessel pair, hosted in a three-dimensional (3D) tumor microenvironment-mimetic hydrogel matrix, termed as the tumor-on-a-chip with bioprinted blood and lymphatic vessel pair (TOC-BBL). The bioprinted blood vessel was perfusable channel with opening on both ends while the bioprinted lymphatic vessel was blinded on one end, both of which were embedded in a hydrogel tumor mass, with vessel permeability individually tunable through optimization of the composition of the bioinks. We demonstrated that systems with different combinations of these bioprinted blood/lymphatic vessels exhibited varying levels of diffusion profiles for biomolecules and anti-cancer drugs. Our TOC-BBL platform mimicking the natural pathway of drug-tumor interactions would have the drug introduced through the perfusable blood vessel, cross the vascular wall into the tumor tissue via diffusion, and eventually drained into the lymphatic vessel along with the carrier flow. Our results suggested that this unique in vitro tumor model containing the bioprinted blood/lymphatic vessel pair may have the capacity of simulating the complex transport mechanisms of certain pharmaceutical compounds inside the tumor microenvironment, potentially providing improved accuracy in future cancer drug screening.Current in vitro anti-tumor drug screening strategies are insufficiently portrayed lacking true perfusion and draining microcirculation systems, which may post significant limitation in reproducing the transport kinetics of cancer therapeutics explicitly. Herein, we report the fabrication of an improved tumor model consisting of bioprinted hollow blood vessel and lymphatic vessel pair, hosted in a three-dimensional (3D) tumor microenvironment-mimetic hydrogel matrix, termed as the tumor-on-a-chip with bioprinted blood and lymphatic vessel pair (TOC-BBL). The bioprinted blood vessel was perfusable channel with opening on both ends while the bioprinted lymphatic vessel was blinded on one end, both of which were embedded in a hydrogel tumor mass, with vessel permeability individually tunable through optimization of the composition of the bioinks. We demonstrated that systems with different combinations of these bioprinted blood/lymphatic vessels exhibited varying levels of diffusion profiles for biomolecules and anti-cancer drugs. Our TOC-BBL platform mimicking the natural pathway of drug-tumor interactions would have the drug introduced through the perfusable blood vessel, cross the vascular wall into the tumor tissue via diffusion, and eventually drained into the lymphatic vessel along with the carrier flow. Our results suggested that this unique in vitro tumor model containing the bioprinted blood/lymphatic vessel pair may have the capacity of simulating the complex transport mechanisms of certain pharmaceutical compounds inside the tumor microenvironment, potentially providing improved accuracy in future cancer drug screening. Current in vitro anti-tumor drug screening strategies are insufficiently portrayed lacking true perfusion and draining microcirculation systems, which may post significant limitation in reproducing the transport kinetics of cancer therapeutics explicitly. Herein, we report the fabrication of an improved tumor model consisting of bioprinted hollow blood vessel and lymphatic vessel pair, hosted in a three-dimensional (3D) tumor microenvironment-mimetic hydrogel matrix, termed as the tumor-on-a-chip with bioprinted blood and lymphatic vessel pair (TOC-BBL). The bioprinted blood vessel was perfusable channel with opening on both ends while the bioprinted lymphatic vessel was blinded on one end, both of which were embedded in a hydrogel tumor mass, with vessel permeability individually tunable through optimization of the composition of the bioinks. We demonstrated that systems with different combinations of these bioprinted blood/lymphatic vessels exhibited varying levels of diffusion profiles for biomolecules and anti-cancer drugs. Our TOC-BBL platform mimicking the natural pathway of drug-tumor interactions would have the drug introduced through the perfusable blood vessel, cross the vascular wall into the tumor tissue via diffusion, and eventually drained into the lymphatic vessel along with the carrier flow. Our results suggested that this unique in vitro tumor model containing the bioprinted blood/lymphatic vessel pair may have the capacity of simulating the complex transport mechanisms of certain pharmaceutical compounds inside the tumor microenvironment, potentially providing improved accuracy in future cancer drug screening. |
Author | Ashfaq, Ramla Maharjan, Sushila Li, Jun Ying, Guoliang Hassan, Shabir Xiao, Haiyan Cheng, Feng Cao, Xia Yue, Kan Zhang, Yu Shrike |
Author_xml | – sequence: 1 givenname: Xia surname: Cao fullname: Cao, Xia organization: Harvard Medical School Cambridge – sequence: 2 givenname: Ramla surname: Ashfaq fullname: Ashfaq, Ramla organization: University of the Punjab – sequence: 3 givenname: Feng surname: Cheng fullname: Cheng, Feng organization: Harvard Medical School Cambridge – sequence: 4 givenname: Sushila surname: Maharjan fullname: Maharjan, Sushila organization: Harvard Medical School Cambridge – sequence: 5 givenname: Jun surname: Li fullname: Li, Jun organization: Harvard Medical School Cambridge – sequence: 6 givenname: Guoliang surname: Ying fullname: Ying, Guoliang organization: Harvard Medical School Cambridge – sequence: 7 givenname: Shabir surname: Hassan fullname: Hassan, Shabir organization: Harvard Medical School Cambridge – sequence: 8 givenname: Haiyan surname: Xiao fullname: Xiao, Haiyan organization: South China University of Technology – sequence: 9 givenname: Kan surname: Yue fullname: Yue, Kan organization: South China University of Technology – sequence: 10 givenname: Yu Shrike orcidid: 0000-0002-0045-0808 surname: Zhang fullname: Zhang, Yu Shrike email: yszhang@research.bwh.harvard.edu organization: Harvard Medical School Cambridge |
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Snippet | Current in vitro antitumor drug screening strategies insufficiently mimic biological systems. They tend to lack true perfusion and draining microcirculation... Current in vitro anti-tumor drug screening strategies are insufficiently portrayed lacking true perfusion and draining microcirculation systems, which may post... Current in vitro anti-tumor drug screening strategies are insufficiently portrayed lacking true perfusion and draining microcirculation systems, which may post... |
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SubjectTerms | Bioengineering Biomolecules bioprinting Blood vessels Computer simulation diffusion Hydrogels lymphatic vessels Materials science Optimization Screening Three dimensional printing Transport Tumors tumor‐on‐a‐chip |
Title | A Tumor‐on‐a‐Chip System with Bioprinted Blood and Lymphatic Vessel Pair |
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