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Engineered liver-derived decellularized extracellular matrix-based three-dimensional tumor constructs for enhanced

Shengchang Luo1,2, Qingqing Wang1,2, Miaoting Li1,2

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Summary

This study engineered a 3D tumor model using decellularized extracellular matrix (dECM) within porous microspheres. This novel platform enhances drug screening accuracy by better mimicking the tumor microenvironment (TME) and improving cell viability.

Keywords:
cancerdecellularized extracellular matrixmicrofluidicspreclinical drug screeningthree-dimensional tumor model

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Area of Science:

  • Biomaterials Science
  • Cancer Biology
  • Microfluidics

Background:

  • Decellularized extracellular matrix (dECM) mimics the tumor microenvironment (TME) for drug screening.
  • Existing dECM models face challenges with morphology control and cell viability.
  • Accurate 3D tumor models are crucial for effective chemotherapeutic agent evaluation.

Purpose of the Study:

  • To engineer a 3D tumor model with improved morphology and cell viability using dECM-PLGA microspheres.
  • To assess the efficacy of this model in replicating tumor drug resistance.
  • To provide a scalable platform for pharmaceutical drug testing.

Main Methods:

  • Utilized a microfluidic approach to encapsulate porcine liver dECM in poly(lactic-co-glycolic acid) (PLGA) porous microspheres (dECM-PLGA PMs).
  • Engineered a 3D tumor model using these dECM-PLGA PMs.
  • Analyzed hepatoma carcinoma cell (HepG2) proliferation and drug resistance (IC50 values).
  • Performed proteomic analysis of dECM to identify bioactive components.

Main Results:

  • dECM-PLGA PMs significantly promoted HepG2 cell proliferation compared to PLGA microspheres alone.
  • The dECM-PLGA PMs model demonstrated replication of tumor drug resistance traits.
  • Proteomic analysis identified bioactive fragments within the dECM contributing to model efficacy.
  • The model overcame challenges of unregulated microstructure and suboptimal cell viability.

Conclusions:

  • Engineered dECM-PLGA PMs provide a robust 3D tumor model with enhanced cell viability and controlled morphology.
  • This model effectively replicates key aspects of the TME, including drug resistance.
  • The developed platform offers a sustainable and scalable solution for preclinical drug testing and pharmaceutical evaluations.