Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks. The microtissues and tissue spheroids are living materials with certain measurable, evolving and potentially controllable composition, material and biological properties. Closely placed tissue spheroids undergo tissue fusion - a process that represents a fundamental biological and biophysical principle of developmental biology-inspired directed tissue self-assembly. It is possible to engineer small segments of an intraorgan branched vascular tree by using solid and lumenized vascular tissue spheroids. Organ printing could dramatically enhance and transform the field of tissue engineering by enabling large-scale industrial robotic biofabrication of living human organ constructs with "built-in" perfusable intraorgan branched vascular tree. Thus, organ printing is a new emerging enabling technology paradigm which represents a developmental biology-inspired alternative to classic biodegradable solid scaffold-based approaches in tissue engineering.

Organ Printing: Tissue Spheroids as Building Blocks

Goal Additive manufacturing, also known as 3D printing, has begun to play a significant role in the field of medical devices. This review aims to provide a comprehensive overview and classification of additively manufactured medical instruments for diagnostics and surgery by identifying medical and technical aspects. Methods A scientific literature search on additively manufactured medical instruments was conducted using the Scopus database. Results We categorized the relevant articles (71) by considering the novelty of each proposed instrument and its clinical application. Then, we analyzed the relevant articles by examining the reasons behind choosing additive manufacturing technology to produce instruments for diagnostics and surgery. Possible customization (27%) and Cost-effectiveness (23%) were the main reasons expressed. Technical specifications of the additive manufacturing technology and the material used were also analyzed, and a tendency of using material extrusion technology (35% of the applications) and polymeric materials (86% of the applications) was shown. Conclusions Additive manufacturing is opening the door to a new approach in the production of medical devices, which allows the complexity of their designs to be pushed to the extreme. However, we found that technical limitations need to be tackled and important aspects such as sterilization or debris contamination are still not considered to be relevant factors during the design and fabrication process. Keeping in mind the challenges of such a new field, additive manufacturing technology can be considered as a great opportunity to provide easy access to healthcare in developing countries as well as an important step toward patient-specific medicine.

Additive manufacturing of medical instruments : A state-of-the-art review

Additive manufacturing in the field of regenerative medicine aims to fabricate organized tissue-equivalents. However, the control over shape and composition of biofabricated constructs is still a challenge and needs to be improved. The current research aims to improve shape, by converging a number of biocompatible, quality construction materials into a single three-dimensional fiber deposition process. To demonstrate this, several models of complex anatomically shaped constructs were fabricated by combined deposition of poly(vinyl alcohol), poly(ε-caprolactone), gelatin methacrylamide/gellan gum and alginate hydrogel. Sacrificial components were co-deposited as temporary support for overhang geometries and were removed after fabrication by immersion in aqueous solutions. Embedding of chondrocytes in the gelatin methacrylamide/gellan component demonstrated that the fabrication and the sacrificing procedure did not affect cell viability. Further, it was shown that anatomically shaped constructs can be successfully fabricated, yielding advanced porous thermoplastic polymer scaffolds, layered porous hydrogel constructs, as well as reinforced cell-laden hydrogel structures. In conclusion, anatomically shaped tissue constructs of clinically relevant sizes can be generated when employing multiple building and sacrificial materials in a single biofabrication session. The current techniques offer improved control over both internal and external construct architecture underscoring its potential to generate customized implants for human tissue regeneration.

Biofabrication of -material anatomically shaped tissue constructs

3D bioprinting is an additive biomanufacturing technology having potential to fast-forward the translational research, as it has the capability to fabricate artificial tissues and organs that closely mimic biological tissues or organs. As an emerging area of research in the field of tissue engineering, 3D bioprinting has scope in the development of implantable tissues and organs, construction of tissue/organ models and high-throughput diseased/cancer models for pharmaceutical and toxicological studies. Further, this area has diversified with the continuous upgradation of 3D bioprinters and biomaterials, which play major roles in the architectural quality and functionality of bioprinted construct. Addressing these technological complexities requires an integrated approach involving expertise from different areas of science and engineering with lateral thinking. In this review, we highlight the recent trends in 3D bioprinting of tissues and organs including recent developments in usage of material, printers and printing technologies. In addition, importance has been given to various target tissues printed using this technology with an emphasis on bioprinted tissue/cancer models.

3D Bioprinting: Recent Trends and Challenges

The need for advancement in biomaterials that stimulate the repair, replacement, or recovery of gentle body tissues and bones keeps growing as the population ages. Although substantial research has been carried out over the last decade to develop medical implants for bone regeneration and healing body tissues, implants still fail due to infection, fracture, corrosion, and extreme load. Depending upon the permanent or temporary implant requirement, various materials such as metals, ceramics, and polymers are used as implantable materials. The article discusses various metals, alloys and polymeric materials and their application as medical implants. Titanium implants have shown promising application as a bone replacement, and their alloys play a critical role in orthopaedic and dental procedures. However, they show various drawbacks such as Ti-6Al-4V alloy shows toxicity, Ti-Zr alloy exhibits lack of mechanical stability and complexity in processing and Ti-Ni alloy show toxicity and low thermal conductivity. Surface modification technique such as PIII&D, CVD, etc., contribute to attaining robust biocompatibility and improving their mechanical properties. Titanium alloys, their properties, and future scope as implantable material have been extensively discussed. Given that biocompatibility and bone response are important determinants of implants’ clinical performance, published studies of in-vitro and in-vivo research have been critically discussed in the article. Bioactivity is an essential characteristic required to stimulate biological response with host tissue and bond with the surrounding tissue. A critical discussion on bioactive materials and enhancement of bioactivity has been included in the article. The paper also examines and discusses several physical and chemical surface modification techniques and their utilization in the development of medical implants. This study discusses biomaterials’ overall performance and applications in biological systems, vital for enhancing medical implants and tissue engineering. This review contains critics for young researchers planning to embark on the development of implants for biomedical applications. 

Recent advancements in nanomaterials for biomedical implants

Bioprinting is a promising technology, which has gained a recent attention, for application in all aspects of human life and has specific advantages in different areas of medicines, especially in ophthalmology. The three-dimensional (3D) printing tools have been widely used in different applications, from surgical planning procedures to 3D models for certain highly delicate organs (such as: eye and heart). The purpose of this paper is to review the dedicated research efforts that so far have been made to highlight applications of 3D printing in the field of ophthalmology.,In this paper, the state-of-the-art review has been summarized for bioprinters, biomaterials and methodologies adopted to cure eye diseases. This paper starts with fundamental discussions and gradually leads toward the summary and future trends by covering almost all the research insights. For better understanding of the readers, various tables and figures have also been incorporated.,The usages of bioprinted surgical models have shown to be helpful in shortening the time of operation and decreasing the risk of donor, and hence, it could boost certain surgical effects. This demonstrates the wide use of bioprinting to design more precise biological research models for research in broader range of applications such as in generating blood vessels and cardiac tissue. Although bioprinting has not created a significant impact in ophthalmology, in recent times, these technologies could be helpful in treating several ocular disorders in the near future.,This review work emphasizes the understanding of 3D printing technologies, in the light of which these can be applied in ophthalmology to achieve successful treatment of eye diseases.

Rajkumar V. Patil

Papers

Bioprinting in ophthalmology: current advances and future pathways