Nanogels for pharmaceutical and biomedical applications and their fabrication using 3D printing technologies

Nanogels are hydrogels formed by connecting nanoscopic micelles dispersed in an aqueous medium, which give an opportunity for incorporating hydrophilic payloads to the exterior of the micellar networks and hydrophobic payloads in the core of the micelles. Biomedical and pharmaceutical applications of nanogels have been explored for tissue regeneration, wound healing, surgical device, implantation, and peroral, rectal, vaginal, ocular, and transdermal drug delivery. Although it is still in the early stages of development, due to the increasing demands of precise nanogel production to be utilized for personalized medicine, biomedical applications, and specialized drug delivery, 3D printing has been explored in the past few years and is believed to be one of the most precise, efficient, inexpensive, customizable, and convenient manufacturing techniques for nanogel production

Scaffolding strategies for tissue engineering and regenerative medicine applications

During the past two decades, tissue engineering and the regenerative medicine field have invested in the regeneration and reconstruction of pathologically altered tissues, such as cartilage, bone, skin, heart valves, nerves and tendons, and many others. The 3D structured scaffolds and hydrogels alone or combined with bioactive molecules or genes and cells are able to guide the development of functional engineered tissues, and provide mechanical support during in vivo implantation. Naturally derived and synthetic polymers, bioresorbable inorganic materials, and respective hybrids, and decellularized tissue have been considered as scaffolding biomaterials, owing to their boosted structural, mechanical, and biological properties. A diversity of biomaterials, current treatment strategies, and emergent technologies used for 3D scaffolds and hydrogel processing, and the tissue-specific considerations for scaffolding for Tissue engineering (TE) purposes are herein highlighted and discussed in depth. The newest procedures focusing on the 3D behavior and multi-cellular interactions of native tissues for further use for in vitro model processing are also outlined. Completed and ongoing preclinical research trials for TE applications using scaffolds and hydrogels, challenges, and future prospects of research in the regenerative medicine field are also presented.This research was funded by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000023) and by the Portuguese Foundation for Science and Technology ((M-ERA-NET/0022/2016), Transitional Rule DL 57/2016 (CTTI-57/18-I3BS(5)), and (IF/01285/2015))

3D Bioprinting tissue analogs: Current development and translational implications

Three-dimensional (3D) bioprinting is a promising and rapidly evolving technology in the field of additive manufacturing. It enables the fabrication of living cellular constructs with complex architectures that are suitable for various biomedical applications, such as tissue engineering, disease modeling, drug screening, and precision regenerative medicine. The ultimate goal of bioprinting is to produce stable, anatomically-shaped, human-scale functional organs or tissue substitutes that can be implanted. Although various bioprinting techniques have emerged to develop customized tissue-engineering substitutes over the past decade, several challenges remain in fabricating volumetric tissue constructs with complex shapes and sizes and translating the printed products into clinical practice. Thus, it is crucial to develop a successful strategy for translating research outputs into clinical practice to address the current organ and tissue crises and improve patients' quality of life. This review article discusses the challenges of the existing bioprinting processes in preparing clinically relevant tissue substitutes. It further reviews various strategies and technical feasibility to overcome the challenges that limit the fabrication of volumetric biological constructs and their translational implications. Additionally, the article highlights exciting technological advances in the 3D bioprinting of anatomically shaped tissue substitutes and suggests future research and development directions. This review aims to provide readers with insight into the state-of-the-art 3D bioprinting techniques as powerful tools in engineering functional tissues and organs

In situ enabling approaches for tissue regeneration: current challenges and new developments

In situ tissue regeneration can be defined as the implantation of tissue-specific biomaterials (by itself or in combination with cells and/or biomolecules) at the tissue defect, taking advantage of the surrounding microenvironment as a natural bioreactor. Up to now, the structures used were based on particles or gels. However, with the technological progress, the materials’ manipulation and processing has become possible, mimicking the damaged tissue directly at the defect site. This paper presents a comprehensive review of current and advanced in situ strategies for tissue regeneration. Recent advances to put in practice the in situ regeneration concept have been mainly focused on bioinks and bioprinting techniques rather than the combination of different technologies to make the real in situ regeneration. The limitation of conventional approaches (e.g., stem cell recruitment) and their poor ability to mimic native tissue are discussed. Moreover, the way of advanced strategies such as 3D/4D bioprinting and hybrid approaches may contribute to overcome the limitations of conventional strategies are highlighted. Finally, the future trends and main research challenges of in situ enabling approaches are discussed considering in vitro and in vivo evidence.info:eu-repo/semantics/publishedVersio

In situ enabling approaches for tissue regeneration: Current challenges and new developments

This work was supported by National Funds from the FCT, Fundação para a Ciência e a Tecnologia, through the projects UID/Multi/50016/2019, UID/Multi/04044/2019, and POCI-01-0145-FEDER-31146, a post-doctoral fellowship to SB-S (SFRH/BPD/116024/2016), the European Union through PT2020 and Centro2020 (CENTRO-01-0145-FEDER-000014 and POCI-01-0247-FEDER-024533), the Fundo Europeu de Desenvolvimento Regional (FEDER) through the project NORTE-01-0145-FEDER-000012 (Biotherapies – Structured Programme on Bioengineering Therapies for Infectious Diseases and Tissue Regeneration) funded by the NORTE2020 program, and the Interreg V-A POCTEP Program through FEDER funds from the European Union (0245_IBEROS_1_E).In situ tissue regeneration can be defined as the implantation of tissue-specific biomaterials (by itself or in combination with cells and/or biomolecules) at the tissue defect, taking advantage of the surrounding microenvironment as a natural bioreactor. Up to now, the structures used were based on particles or gels. However, with the technological progress, the materials’ manipulation and processing has become possible, mimicking the damaged tissue directly at the defect site. This paper presents a comprehensive review of current and advanced in situ strategies for tissue regeneration. Recent advances to put in practice the in situ regeneration concept have been mainly focused on bioinks and bioprinting techniques rather than the combination of different technologies to make the real in situ regeneration. The limitation of conventional approaches (e.g., stem cell recruitment) and their poor ability to mimic native tissue are discussed. Moreover, the way of advanced strategies such as 3D/4D bioprinting and hybrid approaches may contribute to overcome the limitations of conventional strategies are highlighted. Finally, the future trends and main research challenges of in situ enabling approaches are discussed considering in vitro and in vivo evidence.info:eu-repo/semantics/publishedVersio

Fiber-based tissue engineering: Progress, challenges, and opportunities.

Tissue engineering aims to improve the function of diseased or damaged organs by creating biological substitutes. To fabricate a functional tissue, the engineered construct should mimic the physiological environment including its structural, topographical, and mechanical properties. Moreover, the construct should facilitate nutrients and oxygen diffusion as well as removal of metabolic waste during tissue regeneration. In the last decade, fiber-based techniques such as weaving, knitting, braiding, as well as electrospinning, and direct writing have emerged as promising platforms for making 3D tissue constructs that can address the abovementioned challenges. Here, we critically review the techniques used to form cell-free and cell-laden fibers and to assemble them into scaffolds. We compare their mechanical properties, morphological features and biological activity. We discuss current challenges and future opportunities of fiber-based tissue engineering (FBTE) for use in research and clinical practice

Automating the processing steps for obtaining bone tissue engineered substitutes : from imaging tools to bioreactors.

Bone diseases and injuries are highly incapacitating and result in a high demand for tissue substitutes with specific biomechanical and structural features. Tissue engineering has already proven to be effective in regenerating bone tissue but has not yet been able to become an economically viable solution due to the complexity of the tissue which is very difficult to be replicated, eventually requiring the utilization of highly labour-intensive processes. Process automation is seen as the solution for mass production of cellularized bone tissue substitutes at an affordable cost by being able to reduce human intervention as well as reducing product variability. The combination of tools such as medical imaging, computer-aided fabrication and bioreactor technologies, which are currently used in tissue engineering, shows potential to generate automated production ecosystems which will in turn enable the generation of commercially available products with widespread clinical application.The authors would like to acknowledge the partial support by the European Network of Excellence EXPERTISSUES (NMP3-CT-2004-500283). Pedro Costa would also like to acknowledge the Portuguese Foundation for Science and Technology for his PhD grant (SFRH/BD/62452/2009)

Impact of Ear Occlusion on In-Ear Sounds Generated by Intra-oral Behaviors

We conducted a case study with one volunteer and a recording setup to detect sounds induced by the actions: jaw clenching, tooth grinding, reading, eating, and drinking. The setup consisted of two in-ear microphones, where the left ear was semi-occluded with a commercially available earpiece and the right ear was occluded with a mouldable silicon ear piece. Investigations in the time and frequency domains demonstrated that for behaviors such as eating, tooth grinding, and reading, sounds could be recorded with both sensors. For jaw clenching, however, occluding the ear with a mouldable piece was necessary to enable its detection. This can be attributed to the fact that the mouldable ear piece sealed the ear canal and isolated it from the environment, resulting in a detectable change in pressure. In conclusion, our work suggests that detecting behaviors such as eating, grinding, reading with a semi-occluded ear is possible, whereas, behaviors such as clenching require the complete occlusion of the ear if the activity should be easily detectable. Nevertheless, the latter approach may limit real-world applicability because it hinders the hearing capabilities.</p

Intraoperative tissue classification methods in orthopedic and neurological surgeries: A systematic review

Accurate tissue differentiation during orthopedic and neurological surgeries is critical, given that such surgeries involve operations on or in the vicinity of vital neurovascular structures and erroneous surgical maneuvers can lead to surgical complications. By now, the number of emerging technologies tackling the problem of intraoperative tissue classification methods is increasing. Therefore, this systematic review paper intends to give a general overview of existing technologies. The review was done based on the PRISMA principle and two databases: PubMed and IEEE Xplore. The screening process resulted in 60 full-text papers. The general characteristics of the methodology from extracted papers included data processing pipeline, machine learning methods if applicable, types of tissues that can be identified with them, phantom used to conduct the experiment, and evaluation results. This paper can be useful in identifying the problems in the current status of the state-of-the-art intraoperative tissue classification methods and designing new enhanced techniques