3D Tissue Engineered in Vitro Models of Cancer in Bone

Abstract

Biological models are necessary tools for gaining insight into underlying mechanisms governing complex pathologies such as cancer in the bone. Models range from tissue culture systems to models and can be used with corresponding epidemiological and clinical data to understand disease etiology, progression, driver mutations, and signaling pathways. In bone cancer, as with many other cancers, models are often too complex to study specific cell-cell interactions or protein roles, and 2D models are often too simple to accurately represent disease processes. Consequently, researchers have increasingly turned to 3D tissue engineered models as a useful compromise. In this review, tissue engineered 3D models of bone and cancer are described in depth and compared to 2D models. Biomaterials and cell types used are described, and future directions in the field of tissue engineered bone cancer models are proposed.

Prostate Cancer Phenotype Influences Bone Mineralization at Metastasis: A Study Using an In Vitro Prostate Cancer Metastasis Testbed

“…One of the significant barriers for investigating the osteotropic nature of prostate cancer cells has been the lack of availability of an appropriate in vitro model that mimics closely the in vivo bone microenvironment in response to bone–cancer interaction. In recent years, with the development of 3D in vitro models as tools for investigating the molecular mechanism of cancer metastasis, a significant number of novel and innovative 3D models has been reported in an attempt to recapitulate the native tumor microenvironment . However, none of these models used 3D SC of MSCs to generate human bone tissue on bone‐meeting scaffolds prior to seeding prostate cancer cells to recapitulate the unique remodeling of the bone environment.…”

“…In recent years, with the development of 3D in vitro models as tools for investigating the molecular mechanism of cancer metastasis, a significant number of novel and innovative 3D models has been reported in an attempt to recapitulate the native tumor microenvironment. (55)(56)(57) However, none of these models used 3D SC of MSCs to generate human bone tissue on bonemeeting scaffolds prior to seeding prostate cancer cells to recapitulate the unique remodeling of the bone environment. Our 3D SC model consists of prostate cancer cells cultured within an engineered-bone tissue formed by differentiated MSCs.…”

In Vitro 3D Cultures to Reproduce the Bone Marrow Niche

“…Hydrogel, scaffold Breast, prostate, osteosarcoma (63)(64)(65) Chitosan-alginate Scaffold Prostate, glioblastoma, hepatocellular carcinoma (66,67) Hyaluronic acid Scaffold, hydrogel Renal cell carcinoma, MM (68,69) Bacterial nanocellulose Scaffold, hydrogel Neuroblastoma, osteosarcoma, prostate, renal cancer, breast (70,71) Native ECM Scaffold MM, breast (72,73) ECM/cartilaginous matrix/Matrigel Scaffold, hydrogel Breast (74) Chitosan (with or without HA or collagen) Scaffold Breast (75) Cell sheets over medical-grade polycaprolactone-tricalcium phosphate scaffold prostate (76) Synthetic materials Poly(ethylene) glycol Hydrogel Breast, prostate (77)(78)(79) Poly(ε-caprolactone) Hydrogel Breast, prostate, osteosarcoma, Ewing sarcoma (80)(81)(82) Poly(amino acid-)-based polymers Hydrogel Osteosarcoma (83) PLG (nonmineralized) and PLG mineralized with HA Scaffold Breast (84) Adapted with permission from Sitarski and colleagues. (33) BM = bone marrow; ECM = extracellular matrix; HA = hydroxyapatite; MM = multiple myeloma; PLG = poly(lactide-co-glycolide).…”

“…Tumor development is a multistep process, and a series of factors, such as phenotypical heterogeneity, biological context, and heterotypic crosstalk, as well as the microenvironment influence survival and proliferation . Although the 2D models cannot offer these requirements, they do offer some advantages in regard to ease of maintenance, simplicity, and cost effectiveness compared with other tissue culture models, such as 3D and animal models . To mimic human cancer growth, in vivo animal models are also widely used to study cancer cells.…”

“…(32) Although the 2D models cannot offer these requirements, they do offer some advantages in regard to ease of maintenance, simplicity, and cost effectiveness compared with other tissue culture models, such as 3D and animal models. (33) To mimic human cancer growth, in vivo animal models are also widely used to study cancer cells. Animal models can provide a complex physiologic structure that is reasonably similar to the human cell and organ system.…”