Spatially patterned 3D model mimics key features of cancer metastasis to bone.

Bone is the most common target of metastasis in breast cancer and prostate cancer, leading to significant mortality due to lack of effective treatments. The discovery of novel therapies has been hampered by a lack of physiologically relevant in vitro models that can mimic key clinical features of bone metastases. To fill this critical gap, here we report spatially patterned, tissue engineered 3D models of breast cancer and prostate cancer bone metastasis which mimic bone-specific invasion, cancer aggressiveness, cancer-induced dysregulation of bone remodeling, and in vivo drug response.

A 3D Osteosarcoma Model with Bone-Mimicking Cues Reveals a Critical Role of Bone Mineral and Informs Drug Discovery.

Osteosarcoma (OS) is an aggressive bone cancer for which survival has not improved over three decades. While biomaterials have been widely used to engineer 3D soft-tissue tumor models, the potential of engineering 3D biomaterials-based OS models for comprehensive interrogation of OS pathology and drug discovery remains untapped. Bone is characterized by high mineral content, yet the role of bone mineral in OS progression and drug response remains unknown.

Tissue-engineered 3D models for elucidating primary and metastatic bone cancer progression.

Malignant bone tumors are aggressive neoplasms which arise from bone tissue or as a result of metastasis. The most prevalent types of cancer, such as breast, prostate, and lung cancer, all preferentially metastasize to bone, yet the role of the bone niche in promoting cancer progression remains poorly understood. Tissue engineering has the potential to bridge this knowledge gap by providing 3D in vitro systems that can be specifically designed to mimic key properties of the bone niche in a more physiologically relevant context than standard 2D culture.

Mineralized Biomaterials Mediated Repair of Bone Defects Through Endogenous Cells.

Synthetic biomaterials that create a dynamic calcium (Ca)-, phosphate (PO) ion-, and calcium phosphate (CaP)-rich microenvironment, similar to that found in native bone tissue, have been shown to promote osteogenic commitment of stem cells in vitro and in vivo. The intrinsic osteoconductivity and osteoinductivity of such biomaterials make them promising bone grafts for the treatment of bone defects. We thus aimed to evaluate the potential of mineralized biomaterials to induce bone repair of a critical-sized cranial defect in the absence of exogenous cells and growth factors.

Hydrogels as Extracellular Matrix Analogs.

The extracellular matrix (ECM) is the non-cellular component of tissue that provides physical scaffolding to cells. Emerging studies have shown that beyond structural support, the ECM provides tissue-specific biochemical and biophysical cues that are required for tissue morphogenesis and homeostasis. Hydrogel-based platforms have played a key role in advancing our knowledge of the role of ECM in regulating various cellular functions.