Engineering osteoblastic metastases to delineate the adaptive response of androgen-deprived prostate cancer in the bone metastatic microenvironment

Bock, Nathalie; Shokoohmand, Ali; Kryza, Thomas; Röhl, Joan; Meijer, Jonelle; Tran, Phong A.; Nelson, Colleen C.; Clements, Judith A.

doi:10.1038/s41413-019-0049-8

Cited by 34 publications

(46 citation statements)

References 53 publications

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“…In scaffolds with aligned microstructures, cells show better cellular organization when compared with scaffolds where the same microstructures are randomly oriented. 71,72 For example, Bock et al 71 used 3D printing to create a medical-grade polycaprolactone (mPCL) scaffold treated with calcium phosphate to culturing primary human osteoprogenitor cells ( Fig. 4a-Left panel).…”

Section: Applications Of Smart Biomaterials Responding To Internal Mamentioning

confidence: 99%

On the road to smart biomaterials for bone research: definitions, concepts, advances, and outlook

et al. 2021

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The demand for biomaterials that promote the repair, replacement, or restoration of hard and soft tissues continues to grow as the population ages. Traditionally, smart biomaterials have been thought as those that respond to stimuli. However, the continuous evolution of the field warrants a fresh look at the concept of smartness of biomaterials. This review presents a redefinition of the term “Smart Biomaterial” and discusses recent advances in and applications of smart biomaterials for hard tissue restoration and regeneration. To clarify the use of the term “smart biomaterials”, we propose four degrees of smartness according to the level of interaction of the biomaterials with the bio-environment and the biological/cellular responses they elicit, defining these materials as inert, active, responsive, and autonomous. Then, we present an up-to-date survey of applications of smart biomaterials for hard tissues, based on the materials’ responses (external and internal stimuli) and their use as immune-modulatory biomaterials. Finally, we discuss the limitations and obstacles to the translation from basic research (bench) to clinical utilization that is required for the development of clinically relevant applications of these technologies.

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Section: Applications Of Smart Biomaterials Responding To Internal Mamentioning

confidence: 99%

On the road to smart biomaterials for bone research: definitions, concepts, advances, and outlook

et al. 2021

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“…Improved in vitro models that more accurately predict in vivo behavior are vital to the development of the next generation of bone metastatic PCa treatments. Another 3D in vitro platform to study the progression of PCa and its adaptive response in bone microenvironment was developed by Bock et al [ 55 ]. Here, they bioengineered a human osteoblast-derived mineralized microtissue (hOBMT) by seeding human primary osteoprogenitor cells on a calcium phosphate-coated 3D printed scaffold consist of medical-grade poly(caprolactone).…”

Section: Nanomedicine and Prostate Cancer Bone Metastasismentioning

confidence: 99%

Recent Advances in Nanomedicine for the Diagnosis and Treatment of Prostate Cancer Bone Metastasis

et al. 2021

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Patients with advanced prostate cancer can develop painful and debilitating bone metastases. Currently available interventions for prostate cancer bone metastases, including chemotherapy, bisphosphonates, and radiopharmaceuticals, are only palliative. They can relieve pain, reduce complications (e.g., bone fractures), and improve quality of life, but they do not significantly improve survival times. Therefore, additional strategies to enhance the diagnosis and treatment of prostate cancer bone metastases are needed. Nanotechnology is a versatile platform that has been used to increase the specificity and therapeutic efficacy of various treatments for prostate cancer bone metastases. In this review, we summarize preclinical research that utilizes nanotechnology to develop novel diagnostic imaging tools, translational models, and therapies to combat prostate cancer bone metastases.

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“…While this has been heavily investigated for in vivo applications, mPCL is now also used in in vitro cancer models, mostly printed as microfiber 3D architectures enabling seeding and culture of bone cells. In our work (Shokoohmand et al, 2016, 2019; Bock et al, 2019), we have used melt electrospinning combined with additive manufacturing (“melt electrowriting”) to print mPCL microfibers into linear or tubular porous scaffolds populated with primary osteoprogenitors isolated from human bone tissue (Figures 5A–C). By coating the fibers with calcium phosphate and using osteogenic differentiation media, the resulting osteoblast-derived microtissues contained osteoblastic and osteocytic cells with abundant key ECM deposition.…”

Section: Engineering Patient-specific Tumor Microenvironment Modelsmentioning

confidence: 99%

“…By coating the fibers with calcium phosphate and using osteogenic differentiation media, the resulting osteoblast-derived microtissues contained osteoblastic and osteocytic cells with abundant key ECM deposition. The patient-derived microtissues were used as an in vitro mineralized model platform to study prostate cancer growth in bone, by co-culturing cancer lines (Bock et al, 2019) and PDXs (Shokoohmand et al, 2019). In the PDX study (Figures 5D–I), prostate cancer PDX models were used; from lymph node metastasis (LuCaP35) and bone metastasis (BM18).…”

Section: Engineering Patient-specific Tumor Microenvironment Modelsmentioning

confidence: 99%

“…In future, Matrigel could be replaced by attractive synthetic options such GelMA, to avoid a murine component in this otherwise fully human model. Using a similar scaffold design as in Bock et al (2019), melt mPCL electrowritten scaffolds were used to create a osteoblast-like microenvironment, although using differentiated immortalized human MSCs (Figures 5J–M). Two patient-derived PDX samples were dissociated and cultured on top of the mineralized microtissue up to 50 days for 1 patient and 30 days for the other.…”

Section: Engineering Patient-specific Tumor Microenvironment Modelsmentioning

confidence: 99%

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Addressing Patient Specificity in the Engineering of Tumor Models

Bray

Hutmacher

2019

Front. Bioeng. Biotechnol.

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Cancer treatment is challenged by the heterogeneous nature of cancer, where prognosis depends on tumor type and disease stage, as well as previous treatments. Optimal patient stratification is critical for the development and validation of effective treatments, yet pre-clinical model systems are lacking in the delivery of effective individualized platforms that reflect distinct patient-specific clinical situations. Advances in cancer cell biology, biofabrication, and microengineering technologies have led to the development of more complex in vitro three-dimensional (3D) models to act as drug testing platforms and to elucidate novel cancer mechanisms. Mostly, these strategies have enabled researchers to account for the tumor microenvironment context including tumor-stroma interactions, a key factor of heterogeneity that affects both progression and therapeutic resistance. This is aided by state-of-the-art biomaterials and tissue engineering technologies, coupled with reproducible and high-throughput platforms that enable modeling of relevant physical and chemical factors. Yet, the translation of these models and technologies has been impaired by neglecting to incorporate patient-derived cells or tissues, and largely focusing on immortalized cell lines instead, contributing to drug failure rates. While this is a necessary step to establish and validate new models, a paradigm shift is needed to enable the systematic inclusion of patient-derived materials in the design and use of such models. In this review, we first present an overview of the components responsible for heterogeneity in different tumor microenvironments. Next, we introduce the state-of-the-art of current in vitro 3D cancer models employing patient-derived materials in traditional scaffold-free approaches, followed by novel bioengineered scaffold-based approaches, and further supported by dynamic systems such as bioreactors, microfluidics, and tumor-on-a-chip devices. We critically discuss the challenges and clinical prospects of models that have succeeded in providing clinical relevance and impact, and present emerging concepts of novel cancer model systems that are addressing patient specificity, the next frontier to be tackled by the field.

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Engineering osteoblastic metastases to delineate the adaptive response of androgen-deprived prostate cancer in the bone metastatic microenvironment

Cited by 34 publications

References 53 publications

On the road to smart biomaterials for bone research: definitions, concepts, advances, and outlook

On the road to smart biomaterials for bone research: definitions, concepts, advances, and outlook

Recent Advances in Nanomedicine for the Diagnosis and Treatment of Prostate Cancer Bone Metastasis

Addressing Patient Specificity in the Engineering of Tumor Models

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