Regenerative therapies for tympanic membrane

It is estimated that by 2050 one in every ten people will be suffering from disabling hearing loss. Perforated tympanic membranes (TMs) are the most common injury to the human ear, resulting in a partial or complete hearing loss due to inept sound conduction. Commonly known as the eardrum, the TM is a thin, concave tissue of the middle ear that captures sound pressure waves from the environment and transmits them as mechanical vibrations to the inner ear. Microsurgical placement of autologous tissue graft has been the “gold standard” for treating damaged TMs; however, the incongruent structural and mechanical properties of these autografts often impair an optimal hearing restoration following recovery. Moreover, given the lack of available tissues for transplantations, regenerative medicine has emerged as a promising alternative. Several tissue engineered approaches applying bio-instructive scaffolds and stimuli have been reported for the TM regeneration, which can be broadly classified into TM repair and TM reconstruction. This review evaluates the current advantages and challenges of both strategies with a special focus on the use of recent biofabrication technologies for advancing TM tissue engineering

Tympanic Membrane Collagen Expression by Dynamically Cultured Human Mesenchymal Stromal Cell/Star-Branched Poly(ε-Caprolactone) Nonwoven Constructs

The tympanic membrane (TM) primes the sound transmission mechanism due to special fibrous layers mainly of collagens II, III, and IV as a product of TM fibroblasts, while type I is less represented. In this study, human mesenchymal stromal cells (hMSCs) were cultured on star-branched poly("-caprolactone) (*PCL)-based nonwovens using a TM bioreactor and proper dierentiating factors to induce the expression of the TM collagen types. The cell cultures were carried out for one week under static and dynamic conditions. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were used to assess collagen expression. A Finite Element Model was applied to calculate the stress distribution on the scaolds under dynamic culture. Nanohydroxyapatite (HA) was used as a filler to change density and tensile strength of *PCL scaolds. In dynamically cultured *PCL constructs, fibroblast surface marker was overexpressed, and collagen type II was revealed via IHC. Collagen types I, III and IV were also detected. Von Mises stress maps showed that during the bioreactor motion, the maximum stress in *PCL was double that in HA/*PCL scaolds. By using a *PCL nonwoven scaold, with suitable physico-mechanical properties, an oscillatory culture, and proper dierentiative factors, hMSCs were committed into fibroblast lineage-producing TM-like collagens

Cell bioprinting: The 3D-bioplotter™ case

The classic cell culture involves the use of support in two dimensions, such as a well plate or a Petri dish, that allows the culture of different types of cells. However, this technique does not mimic the natural microenvironment where the cells are exposed to. To solve that, three-dimensional bioprinting techniques were implemented, which involves the use of biopolymers and/or synthetic materials and cells. Because of a lack of information between data sources, the objective of this review paper is, to sum up, all the available information on the topic of bioprinting and to help researchers with the problematics with 3D bioprinters, such as the 3D-Bioplotter™. The 3D-Bioplotter™ has been used in the pre-clinical field since 2000 and could allow the printing of more than one material at the same time, and therefore to increase the complexity of the 3D structure manufactured. It is also very precise with maximum flexibility and a user-friendly and stable software that allows the optimization of the bioprinting process on the technological point of view. Different applications have resulted from the research on this field, mainly focused on regenerative medicine, but the lack of information and/or the possible misunderstandings between papers makes the reproducibility of the tests dicult. Nowadays, the 3D Bioprinting is evolving into another technology called 4D Bioprinting, which promises to be the next step in the bioprinting field and might promote great applications in the future

Analysis of cognitive framework and biomedical translation of tissue engineering in otolaryngology

Tissue engineering is a relatively recent research area aimed at developing artificial tissues that can restore, maintain, or even improve the anatomical and/or functional integrity of injured tissues. Otolaryngology, as a leading surgical specialty in head and neck surgery, is a candidate for the use of these advanced therapies and medicinal products developed. Nevertheless, a knowledge-based analysis of both areas together is still needed. The dataset was retrieved from the Web of Science database from 1900 to 2020. SciMAT software was used to perform the science mapping analysis and the data for the biomedical translation identification was obtained from the iCite platform. Regarding the analysis of the cognitive structure, we find consolidated research lines, such as the generation of cartilage for use as a graft in reconstructive surgery, reconstruction of microtia, or the closure of perforations of the tympanic membrane. This last research area occupies the most relevant clinical translation with the rest of the areas presenting a lower translational level. In conclusion, Tissue engineering is still in an early translational stage in otolaryngology, otology being the field where most advances have been achieved. Therefore, although otolaryngologists should play an active role in translational research in tissue engineering, greater multidisciplinary efforts are required to promote and encourage the translation of potential clinical applications of tissue engineering for routine clinical use.Spanish State Research Agency through the project PID2019-105381GAI00/ AEI/10.13039/501100011033 (iScience)CTS-115 (Tissue Engineering Research Group, University of Granada) from Junta de Andalucia, Spai

Three-Dimensional Printing and Its Applications in Otorhinolaryngology–Head and Neck Surgery

Objective Three-dimensional (3D)-printing technology is being employed in a variety of medical and surgical specialties to improve patient care and advance resident physician training. As the costs of implementing 3D printing have declined, the use of this technology has expanded, especially within surgical specialties. This article explores the types of 3D printing available, highlights the benefits and drawbacks of each methodology, provides examples of how 3D printing has been applied within the field of otolaryngology–head and neck surgery, discusses future innovations, and explores the financial impact of these advances. Data Sources Articles were identified from PubMed and Ovid MEDLINE. Review Methods PubMed and Ovid Medline were queried for English articles published between 2011 and 2016, including a few articles prior to this time as relevant examples. Search terms included 3-dimensional printing, 3D printing, otolaryngology, additive manufacturing, craniofacial, reconstruction, temporal bone, airway, sinus, cost, and anatomic models. Conclusions Three-dimensional printing has been used in recent years in otolaryngology for preoperative planning, education, prostheses, grafting, and reconstruction. Emerging technologies include the printing of tissue scaffolds for the auricle and nose, more realistic training models, and personalized implantable medical devices. Implications for Practice After the up-front costs of 3D printing are accounted for, its utilization in surgical models, patient-specific implants, and custom instruments can reduce operating room time and thus decrease costs. Educational and training models provide an opportunity to better visualize anomalies, practice surgical technique, predict problems that might arise, and improve quality by reducing mistakes

Silk fibroin as a functional biomaterial for tissue engineering

Tissue engineering (TE) is the approach to combine cells with scaffold materials and appropriate growth factors to regenerate or replace damaged or degenerated tissue or organs. The scaffold material as a template for tissue formation plays the most important role in TE. Among scaffold materials, silk fibroin (SF), a natural protein with outstanding mechanical properties, biodegradability, biocompatibility, and bioresorbability has attracted significant attention for TE applications. SF is commonly dissolved into an aqueous solution and can be easily reconstructed into different material formats, including films, mats, hydrogels, and sponges via various fabrication techniques. These include spin coating, electrospinning, freeze drying, physical, and chemical crosslinking techniques. Furthermore, to facilitate fabrication of more complex SF-based scaffolds with high precision techniques including micro-patterning and bio-printing have recently been explored. This review introduces the physicochemical and mechanical properties of SF and looks into a range of SF-based scaffolds that have been recently developed. The typical TE applications of SF-based scaffolds including bone, cartilage, ligament, tendon, skin, wound healing, and tympanic membrane, will be highlighted and discussed, followed by future prospects and challenges needing to be addressed

Functional 3D Printed Polymeric Materials

Additive manufacturing (AM) is an emerging 3D printing technology that enables the design and rapid manufacturing of materials with complex microstructures. Advances in 3D printing have allowed manufacturing companies to expand from design and 3D printing of prototypes to the rapid manufacturing of end products. Additive manufacturing enables the manufacturing of components in a layer-by-layer fashion, opposite to common manufacturing methods that rely on machining, molding and subtractive methods to obtain the final product. AM employs a computer-aided design software that allows for the design of virtual objects and the control of the nozzle and/or stage of the 3D printer. Due to their versatility and wide range of mechanical and chemical properties, polymers are the most utilized materials for AM. Polymers used for AM covers thermoplastics, thermosets, elastomers, polymers with incorporated fillers, biopolymers, and polymers blended with biological materials. The architectural design and choice of polymers can lead to materials with enhanced functionalities, mechanical properties, porosity, and stability. This chapter focuses on the development of polymer-based 3D printing materials with multifunctionalities used specifically for the production of biomedical devices, electronic devices, and aerospace-relevant products

New frontiers and emerging applications of 3D printing in ENT surgery: A systematic review of the literature

3D printing systems have revolutionised prototyping in the industrial field by lowering production time from days to hours and costs from thousands to just a few dollars. Today, 3D printers are no more confined to prototyping, but are increasingly employed in medical disci- plines with fascinating results, even in many aspects of otorhinolaryngology. All publications on ENT surgery, sourced through updated electronic databases (PubMed, MEDLINE, EMBASE) and published up to March 2017, were examined according to PRISMA guidelines. Overall, 121 studies fulfilled specific inclusion criteria and were included in our systematic review. Studies were classified according to the specific field of application (otologic, rhinologic, head and neck) and area of interest (surgical and preclinical education, customised surgical planning, tissue engineering and implantable prosthesis). Technological aspects, clinical implications and limits of 3D printing processes are discussed focusing on current benefits and future perspectives

3D bioprinting for auricular reconstruction: A review and future perspectives

Congenital abnormalities or acquired trauma to the auricle can result in a need for ear reconstruction and negatively impact a person’s quality of life. Autografting, alloplastic implants, and prostheses are available to treat these issues, but each requires multiple surgical stages and has limitations and complications. Three-dimensional (3D) bioprinting promises to allow the creation of living, patient-specific ear substitutes that could reduce operative morbidity. In this review, we evaluate the current state of 3D bioprinting methods through a systematic search and review of 27 studies, aiming to examine this emerging technology within the context of existing reconstructive options. The included studies were all non-randomized experimental studies, except for a single pilot clinical trial. Most of these studies involved both in vitro and in vivo experiments demonstrating the potential of 3D bioprinting to create functional and anatomically accurate engineered cartilaginous frameworks for surgical implantation. Various ways of optimizing printing were identified, from choosing the most suitable material and cell type for the construct to addressing scaffold deformation and shrinkage issues. 3D printing has the potential to revolutionize reconstructive ear surgery by creating functional and aesthetically pleasing auricles. While more research into printing parameters, bioinks, cell types, and materials could optimize results, the next step is to conduct long-term in vivo clinical trials in humans