3D Bio-Printed Glioblastoma-Vascular Niche Models

Introduction Glioblastoma multiforme(GBM),a malignant brain tumor,is highly invasive and use brain microvessels to migrate and invade.Studying the perivascular invasion/migration of GBM may enable new possibilities in GBM therapy.However,the lack proper 3D study models that recapitulate GBM hallmarks restricts investigating cell-cell/cell-molecular interactions in tumor microenvironments.In this study,we created GBM-vascular niche models through 3D bioprinting [1-2] using patient-derived GBM cells with sternness(GSC:glioblastoma stem cells),vasculature endothelial cells(ECs),mural cells,and various hydrogels.Materials and methods Three GBM-vascular models were designed:Model A with large vessels and GBM spheroid;Model B with large-and micro-vessels,and GBM spheroid;Model C with large-and micro-vessels and scattered GBM cells.Large channels were created by sacrificial bioprinting.Microvessel network was formed through self-assembly of ECs(HUVEC or brain EC)and mural cells(fibroblast,pericytes,and/or astrocytes).Three GBM cell types were used in the study:SD02 and SD03 are GSCs;U87MG is a commercially-available GBM cell line.Collagen type I or fibrin hydrogel have been used as major scaffold materials.For drug treatment,Temozolomide in culture medium was perfused through large vasculatures in Model A.Results and discussion Three different GBM-vascular models were successfully fabricated and culture for 2-10.GSCs cultured in these models maintained sternness and heterogeneity during the long-term cultures.In Model A,GSCs actively invaded into the surrounding tissues(~Day26),initially regressed in response to the drug(~Day50),then developed therapeutic resistance and resumed aggressive invasion(~Day57).In Model B and C,three GBM types presented distinctive invasion patterns and EC-interactions.SD02 cells showed a spiky invasion pattern with elongated morphology.SD03 cells showed a more dispersed invasion pattern with many single cell migrations towards surrounding microvessels.U87MG cells showed a blunt invasion pattern,caused EC death in the spheroid form;however,the EC death was significantly reduced in the scattered single cell form.Conclusions In this study,we have created GBM-vascular niche models that can recapitulate various GBM characteristics such as cancer sternness,tumor type-specific invasion patterns,and drug responses with therapeutic resistance.Our models have a great potential in investigating patient-specific tumor behaviors under chemo-/radio-therapy conditions and consequentially helping to tailor personalized treatment strategy.The model platform is capable of modifying multiples variables including ECMs,cell types,vascular structures,and dynamic culture condition.Thus,it can be adapted to other biological systems and serve as a valuable tool for generating customized microenvironments.

Composite bioabsorbable vascular stents via 3D bio-printing and electrospinning for treating stenotic vessels

A new type of vascular stent is designed for treating stenotic vessels. Aiming at overcoming the shortcomings of existing equipment and technology for preparing a bioabsorbable vascular stent （BVS）, a new method which combines 3D bio-printing and electrospinning to prepare the composite bioabsorbable vascular stent （CBVS） is proposed. The inner layer of the CBVS can be obtained through 3D bio- printing using poly-p-dioxanone （PPDO）. The thin nanofiber film that serves as the outer layer can be built through electrospinning using mixtures of chitosan-PVA （poly （vinyl alcohol））. Tests of mechanical properties show that the stent prepared through 3D bio-printing combined with electrospinning is better than that prepared through 3D bio- printing alone. Cells cultivated on the CBVS adhere and proliferate better due to the natural, biological chitosan in the outer layer. The proposed complex process and method can provide a good basis for preparing a controllable drug-carrying vascular stent. Overall, the CBVS can be a good candidate for treating stenotic vessels.

Three-dimensional bio-printing: A new frontier in oncology research

Current research in oncology deploys methods that rely principally on two-dimensional(2D) mono-cell cultures and animal models.Although these methodologies have led to significant advancement in the development of novel experimental therapeutic agents with promising anticancer activity in the laboratory, clinicians still struggle to manage cancer in the clinical setting.The disappointing translational success is attributable mainly to poor representation and recreation of the cancer microenvironment present in human neoplasia.Threedimensional(3D) bio-printed models could help to simulate this micro-environment, with recent bio-printing of live human cells demonstrating that effective in vitro replication is achievable.This literature review outlines up-to-date advancements and developments in the use of 3D bio-printed models currently being used in oncology research.These innovative advancements in 3D bio-printing open up a new frontier for oncology research and could herald an era of progressive clinical cancer therapeutics.

Interaction and the Genesis of Experience: A Phenomenological Contribution for Meaningful Embodied Artificial Intelligence

In this article I will address the issue of the meaning of Embodied Artificial Intelligence(EAI)as it is configured today.My starting point is the refined interactive perspective on the semantics of EAI,as was recently suggested by Froese and colleagues.This perspective rests on the assumption that the concept of human bodily subjectivity must be extended to include meaning-making processes,which are enabled by advanced AI systems that may be incorporated in the human biological body.After having clarified the technical background,I will introduce the genetic component of the phenomenological method as a suitable tool to face the aforementioned issue.Towards this end,I will place the genetic method in the context of the so-called New Human-Machine Interaction(New HMI).I will further outline a genetic phenomenology of visual embodiment,suggesting a futuristic application based on the thesis of the“technological supplementation of phenomenological methodology”through the synthetic method.The case at stake is that of patients with a severe clinical picture characterised by the loss of corneal function,who in the near future could be treated with synthetic corneal prosthetic implants produced by a 3D bio-printing process by using an advanced EAI technique.I will conclude this article with a brief review of the main problems that still remain open.

Three-dimensional printing: review of application in medicine and hepatic surgery

Three-dimensional(3D) printing(3DP) is a rapid prototyping technology that has gained increasing recognition in many different fields. Inherent accuracy and low-cost property enable applicability of 3DP in many areas, such as manufacturing, aerospace,medical, and industrial design. Recently, 3DP has gained considerable attention in the medical field. The image data can be quickly turned into physical objects by using 3DP technology. These objects are being used across a variety of surgical specialties. The shortage of cadaver specimens is a major problem in medical education. However, this concern has been solved with the emergence of 3DP model. Custom-made items can be produced by using 3DP technology. This innovation allows 3DP use in preoperative planning and surgical training. Learning is difficult among medical students because of the complex anatomical structures of the liver. Thus, 3D visualization is a useful tool in anatomy teaching and hepatic surgical training. However,conventional models do not capture haptic qualities. 3DP can produce highly accurate and complex physical models. Many types of human or animal differentiated cells can be printed successfully with the development of 3D bio-printing technology. This progress represents a valuable breakthrough that exhibits many potential uses, such as research on drug metabolism or liver disease mechanism. This technology can also be used to solve shortage of organs for transplant in the future.

Three-dimensional bio-printing of decellularized extracellular matrix-based bio-inks for cartilage regeneration:a systematic review

Cartilage injuries are common problems that increase with the population aging.Cartilage is an avascular tissue with a relatively low level of cellular mitotic activity,which makes it impossible to heal spontaneously.To compensate for this problem,three-dimensional bio-printing has attracted a great deal of attention in cartilage tissue engineering.This emerging technology aims to create three-dimensional functional scaffolds by accurately depositing layer-by-layer bio-inks composed of biomaterial and cells.As a novel bio-ink,a decellularized extracellular matrix can serve as an appropriate substrate that contains all the necessary biological cues for cellular interactions.Here,this review is intended to provide an overview of decellularized extracellular matrix-based bio-inks and their properties,sources,and preparation process.Following this,decellularized extracellular matrix-based bio-inks for cartilage tissue engineering are discussed,emphasizing cell behavior and in-vivo applications.Afterward,the current challenges and future outlook will be discussed to determine the conclusing remarks.

Tumor organoids:synergistic applications,current challenges,and future prospects in cancer therapy

Patient-derived cancer cells(PDCs)and patient-derived xenografts(PDXs)are often used as tumor models,but have many shortcomings.PDCs not only lack diversity in terms of cell type,spatial organization,and microenvironment but also have adverse effects in stem cell cultures,whereas PDX are expensive with a low transplantation success rate and require a long culture time.In recent years,advances in three-dimensional(3D)organoid culture technology have led to the development of novel physiological systems that model the tissues of origin more precisely than traditional culture methods.Patient-derived cancer organoids bridge the conventional gaps in PDC and PDX models and closely reflect the pathophysiological features of natural tumorigenesis and metastasis,and have led to new patient-specific drug screening techniques,development of individualized treatment regimens,and discovery of prognostic biomarkers and mechanisms of resistance.Synergistic combinations of cancer organoids with other technologies,for example,organ-on-a-chip,3D bio-printing,and CRISPR-Cas9-mediated homology-independent organoid transgenesis,and with treatments, such as immunotherapy, have been useful in overcoming their limitations and led to the development of more suitable model systems that recapitulate the complex stroma of cancer, inter-organ and intra-organ communications,and potentially multiorgan metastasis. In this review, we discuss various methods for the creation of organ-specific cancer organoids and summarize organspecific advances and applications, synergistic technologies, and treatments aswell as current limitations and future prospects for cancer organoids. Furtheradvances will bring this novel 3D organoid culture technique closer to clinicalpractice in the future.