Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments

Abstract

Purpose of Review Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. Recent Findings 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment. This review will discuss 3D models including polyurethane, silk, and collagen scaffolds that have been developed to study tumor-induced bone disease. In addition, we discuss 3D printing techniques used to better replicate the structure of bone. Summary 3D models that better replicate the bone microenvironment will help researchers better understand the dynamic interactions between tumors and the bone microenvironment, ultimately leading to better models for testing therapeutics and predicting patient outcomes.

Hallmarks of Bone Metastasis

“…There is now ample evidence that breast cancer cells sense the modulus and mechanics of the local environment both in the primary tumor and at the bone metastatic site through integrin signaling. Cancer cells alter downstream signaling in response to mechanical changes in the environment, where increased stiffness of the environment typically promotes tumor progression [43–45]. Tumor cells seeded onto rigid substrates up-regulate factors that directly promote osteolysis through downstream osteoclast activation (e.g., via PTHrP).…”

Scaffolding Strategies for Tissue Engineering and Regenerative Medicine Applications

“…Several studies have focused on the 3D character and multi-cellular interactions of native tissues, envisioning these 3D technologies as ideal for TERM in vitro model processing. The superior complexity and hierarchy of 3D engineered models have proved to better mimic the natural ECM of damaged tissues, simulating interactions between healthy–unhealthy cell types and the influence of the physical microstructure and mechanical properties of the native tissues [36]. Thus, the biomaterials, approaches, and emerging technologies applied for 3D scaffolds and processing of hydrogel matrices according to the final TERM application and native tissue complexity are herein presented.…”

Biomedical applications of silkworm ( Bombyx Mori ) proteins in regenerative medicine (a narrative review)

“…Despite advances in bone regenerative medicine, current treatments options such as autograftings and allograftings are still severely limited; therefore, musculoskeletal tissue engineering has been used for bone tissue reconstruction (Ma et al, 2018) has an inherent ability to regenerate; however, in many situations, strategies to improve bone repair capacity are still required. Not only the type of defect has a great impact on bone regeneration, but also age, metabolic condition, and the severity of the trauma, influence the likelihood of normal bone healing of those bone fractures (Farokhi et al, 2018;Kwakwa et al, 2017). Silk fibroin has been used to prepare a variety of nanoscale structures, including a nanofibrous matrix and nanoparticles that could be used in bone tissue engineering (Midha et al, 2016).…”