Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.

3D bioprinting of tissues and organs

Additive manufacturing (AM) alias 3D printing translates computer-aided design (CAD) virtual 3D models into physical objects. By digital slicing of CAD, 3D scan, or tomography data, AM builds objects layer by layer without the need for molds or machining. AM enables decentralized fabrication of customized objects on demand by exploiting digital information storage and retrieval via the Internet. The ongoing transition from rapid prototyping to rapid manufacturing prompts new challenges for mechanical engineers and materials scientists alike. Because polymers are by far the most utilized class of materials for AM, this Review focuses on polymer processing and the development of polymers and advanced polymer systems specifically for AM. AM techniques covered include vat photopolymerization (stereolithography), powder bed fusion (SLS), material and binder jetting (inkjet and aerosol 3D printing), sheet lamination (LOM), extrusion (FDM, 3D dispensing, 3D fiber deposition, and 3D plotting), and 3D bioprinting....

Polymers for 3D Printing and Customized Additive Manufacturing

A challenge for tissue engineering is producing three-dimensional (3D), vascularized cellular constructs of clinically relevant size, shape and structural integrity. We present an integrated tissue-organ printer (ITOP) that can fabricate stable, human-scale tissue constructs of any shape. Mechanical stability is achieved by printing cell-laden hydrogels together with biodegradable polymers in integrated patterns and anchored on sacrificial hydrogels. The correct shape of the tissue construct is achieved by representing clinical imaging data as a computer model of the anatomical defect and translating the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations. The incorporation of microchannels into the tissue constructs facilitates diffusion of nutrients to printed cells, thereby overcoming the diffusion limit of 100-200 μm for cell survival in engineered tissues. We demonstrate capabilities of the ITOP by fabricating mandible and calvarial bone, cartilage and skeletal muscle. Future development of the ITOP is being directed to the production of tissues for human applications and to the building of more complex tissues and solid organs.

A 3D bioprinting system to produce human-scale tissue constructs with structural integrity

http://www.tissueeng.net/lab/papers/1-s2.0-S014296121500719X-main.pdf

Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels

We demonstrate the additive manufacturing of complex three-dimensional (3D) biological structures using soft protein and polysaccharide hydrogels that are challenging or impossible to create using traditional fabrication approaches. These structures are built by embedding the printed hydrogel within a secondary hydrogel that serves as a temporary, thermoreversible, and biocompatible support. This process, termed freeform reversible embedding of suspended hydrogels, enables 3D printing of hydrated materials with an elastic modulus <500 kPa including alginate, collagen, and fibrin. Computer-aided design models of 3D optical, computed tomography, and magnetic resonance imaging data were 3D printed at a resolution of ~200 μm and at low cost by leveraging open-source hardware and software tools. Proof-of-concept structures based on femurs, branched coronary arteries, trabeculated embryonic hearts, and human brains were mechanically robust and recreated complex 3D internal and external anatomical architectures.

Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels.

Analyzing electrolytes in urine, such as sodium, potassium, calcium, chloride, and nitrite, has significant diagnostic value in detecting various conditions, such as kidney disorder, urinary stone disease, urinary tract infection, and cystic fibrosis. Ideally, by regularly monitoring these ions with the convenience of dipsticks and portable tools, such as cellphones, informed decision making is possible to control the consumption of these ions. Here, we report a paper-based sensor for measuring the concentration of sodium, potassium, calcium, chloride, and nitrite in urine, accurately quantified using a smartphone-enabled platform. By testing the device with both Tris buffer and artificial urine containing a wide range of electrolyte concentrations, we demonstrate that the proposed device can be used for detecting potassium, calcium, chloride, and nitrite within the whole physiological range of concentrations, and for binary quantification of sodium concentration.

/pdf/sensing-of-electrolytes-in-urine-using-a-miniaturized-paper-4798lnreo3.pdf

Sensing of electrolytes in urine using a miniaturized paper-based device.

Three-dimensional neural tissue engineering has made great strides in developing neural disease models and replacement tissues for patients. However, the need for biomimetic tissue models and effective patient therapies remains unmet. The recent push to expand 2D neural tissue engineering into the third dimension shows great potential to advance the field. Another area which has much to offer to neural tissue engineering is stem cell research. Stem cells are well known for their self-renewal and differentiation potential and have been shown to give rise to tissues with structural and functional properties mimicking natural organs. Application of these capabilities to 3D neural tissue engineering may be highly useful for basic research on neural tissue structure and function, engineering disease models, designing tissues for drug development, and generating replacement tissues with a patient's genetic makeup. Here, we discuss the vast potential, as well as the current challenges, unique to integration of 3D fabrication strategies and stem cells into neural tissue engineering. We also present some of the most significant recent achievements, including nerve guidance conduits to facilitate better healing of nerve injuries, functional 3D biomimetic neural tissue models, physiologically relevant disease models for research purposes, and rapid and effective screening of potential drugs.

/pdf/utilizing-stem-cells-for-three-dimensional-neural-tissue-282smnq3dj.pdf

Utilizing stem cells for three-dimensional neural tissue engineering

Since a three-dimensional (3D) printed drug was first approved by the Food and Drug Administration in 2015, there has been a growing interest in 3D printing for drug manufacturing There are multiple 3D printing methods - including selective laser sintering, binder deposition, stereolithography, inkjet printing, extrusion-based printing, and fused deposition modeling - which are compatible with printing drug products, in addition to both polymer filaments and hydrogels as materials for drug carriers We see the adaptability of 3D printing as a revolutionary force in the pharmaceutical industry Release characteristics of drugs may be controlled by complex 3D printed geometries and architectures Precise and unique doses can be engineered and fabricated via 3D printing according to individual prescriptions On-demand printing of drug products can be implemented for drugs with limited shelf life or for patient-specific medications, offering an alternative to traditional compounding pharmacies For these reasons, 3D printing for drug manufacturing is the future of pharmaceuticals, making personalized medicine possible while also transforming pharmacies

http://ijb.whioce.com/index.php/int-j-bioprinting/article/download/119/pdf

3D printing for drug manufacturing: A perspective on the future of pharmaceuticals.

Readily deployable, low-cost point-of-care medical devices such as lateral flow assays (LFAs), microfluidic paper-based analytical devices (μPADs), and microfluidic thread-based analytical devices (μTADs) are urgently needed in resource-poor settings. Governed by the ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverability) set by the World Health Organization, these reliable platforms can screen a myriad of chemical and biological analytes including viruses, bacteria, proteins, electrolytes, and narcotics. The Ebola epidemic in 2014 and the ongoing pandemic of SARS-CoV-2 have exemplified the ever-increasing importance of timely diagnostics to limit the spread of diseases. This review provides a comprehensive survey of LFAs, μPADs, and μTADs that can be deployed in resource-limited settings. The subsequent commercialization of these technologies will benefit the public health, especially in areas where access to healthcare is limited.

Low-Cost Optical Assays for Point-of-Care Diagnosis in Resource-Limited Settings.

Human papillomavirus (HPV) has been shown in many studies as a prerequisite for the development of cervical cancer, which is the second most common and predominant form of malignancy among women worldwide, with 270 000 deaths (80% of whom live in developing countries) and 500 000 new cases per year. Early diagnosis of cervical cancer allows patients to be fully treated. Therefore, there is high clinical utility of HPV diagnostics even with binary positive/negative indication of the presence of HPV in patient samples. Although the Pap smear is widely used for cervical cancer screening, this method still suffers from low sensitivity and specificity. Thus, simple, rapid and inexpensive diagnostic methods are needed to detect the etiology of cervical cancer, i.e., HPV, especially high-risk oncogenic subtypes 16 and 18. Here, we review the existing assays and platforms employed for HPV diagnosis, and highlight recent advances in nanotechnology and microfluidics that potentially enable new approaches for HPV diagnosis.

Savas Tasoglu

Papers

Sensing of electrolytes in urine using a miniaturized paper-based device.

Utilizing stem cells for three-dimensional neural tissue engineering

3D printing for drug manufacturing: A perspective on the future of pharmaceuticals.

Low-Cost Optical Assays for Point-of-Care Diagnosis in Resource-Limited Settings.

Advances in Nanotechnology and Microfluidics for Human Papillomavirus Diagnostics