Abstract

After cardiovascular disease, cancer is the leading cause of death worldwide with devastating health and economic consequences, particularly in developing countries. Inter-patient variations in anti-cancer drug responses further limit the success of therapeutic interventions. Therefore, personalized medicines approach is key for this patient group involving molecular and genetic screening and appropriate stratification of patients to treatment regimen that they will respond to. However, the knowledge related to adequate risk stratification methods identifying patients who will respond to specific anti-cancer agents is still lacking in many cancer types. Recent advancements in three-dimensional (3D) bioprinting technology, have been extensively used to generate representative bioengineered tumor in vitro models, which recapitulate the human tumor tissues and microenvironment for high-throughput drug screening. Bioprinting process involves the precise deposition of multiple layers of different cell types in combination with biomaterials capable of generating 3D bioengineered tissues based on a computer-aided design. Bioprinted cancer models containing patient-derived cancer and stromal cells together with genetic material, extracellular matrix proteins and growth factors, represent a promising approach for personalized cancer therapy screening. Both natural and synthetic biopolymers have been utilized to support the proliferation of cells and biological material within the personalized tumor models/implants. These models can provide a physiologically pertinent cell–cell and cell–matrix interactions by mimicking the 3D heterogeneity of real tumors. Here, we reviewed the potential applications of 3D bioprinted tumor constructs as personalized in vitro models in anticancer drug screening and in the establishment of precision treatment regimens.

Highlights

  • Despite extensive research, the survival and the quality of life with certain types of cancer are still poor, accounting for millions of deaths worldwide [1,2,3]

  • We provide a comprehensive summary of the collective findings in relation to various bioprinted cancer models utilized for chemotherapeutic drug screening. 2D and 3D cancer models are critically evaluated and comprehensively compared, in terms of their ability to recapitulate physiological tumors and their microenvironment

  • Skin cancer or melanoma is one of the most common forms of cancers especially in Caucasian people consisting of different cancer types including non-melanoma skin cancer (NMSC), malignant melanomas (MM), Merkel cell carcinomas (MCC), basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas, that affects over 300,000 people annually across the globe [152]

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Summary

Introduction

The survival and the quality of life with certain types of cancer are still poor, accounting for millions of deaths worldwide [1,2,3]. Hypoxia or low oxygen can lead to excessive cell proliferation within tumor tissue; highly proliferative cancer cells can generate local hypoxia within tumors under in vivo conditions increasing the percentage of non-proliferating viable hypoxic tumor and/or cancer stem cells [14] These features of tumor tissue are not recapitulated in 2D monolayer cultures [15] and 3D cancer models have better physiological relevance for testing drug treatments and understanding disease mechanisms. The bioprinting field has had substantial technological advances in the last five years becoming the most promising approach for developing 3D constructs of tumor tissue that can be used as models for studying cancer biology and screening anticancer agents [18]. This review clearly outlines current challenges and prospects for 3D bioprinting technologies in cancer research by focusing on the clinical application of these technologies for chemotherapeutic drug screening and the development of personalized treatment regimens for cancer patients

Precision anticancer drug screening
Two- and three-dimensional cell culture systems in cancer research
An overview of 3D bioprinting
Utilization of cancer cells and stromal cells in 3D bioprinted cancer models
Bioinks for cancer bioprinting
Bioprinted breast cancer models
Bioprinted brain tumor models
Bioprinted skin cancer models
Bioprinted colorectal cancer models
Bioprinted cervical cancer models
Bioprinted pancreatic cancer models
Bioprinted ovarian cancer models
Bioprinted lung cancer models
Bioprinted liver cancer models
Challenges and prospects
Findings
Conclusions

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