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 inAdvanced functional materials Vol. 29; no. 31
Main Authors Cao, Xia, Ashfaq, Ramla, Cheng, Feng, Maharjan, Sushila, Li, Jun, Ying, Guoliang, Hassan, Shabir, Xiao, Haiyan, Yue, Kan, Zhang, Yu Shrike
Format Journal Article
LanguageEnglish
Published Hoboken 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.
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
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  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
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fadfm.201807173
https://www.proquest.com/docview/2265696574
https://www.proquest.com/docview/2449994348
https://pubmed.ncbi.nlm.nih.gov/PMC7546431
Volume 29
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