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The global shortage of corneal transplants has spurred an urgency in the quest for efficient treatments. This systematic review not only provides a concise overview of the current landscape of corneal morphology, physiology, diseases, and conventional treatments but crucially delves into the forefront of tissue engineering for corneal regeneration. Emphasizing cellular and acellular components, bioprinting techniques, and pertinent biological assays, it explores optimization strategies for manufacturing and cost-effectiveness. To bridge the gap between research and industrial production, the review outlines the essential regulatory strategy required in Europe, encompassing relevant directives, frameworks, and governing bodies. This comprehensive regulatory framework spans the entire process, from procuring initial components to marketing and subsequent product surveillance. In a pivotal shift towards the future, the review culminates by highlighting the latest advancements in this sector, particularly the integration of tissue therapy with artificial intelligence. This synergy promises substantial optimization of the overall process, paving the way for unprecedented breakthroughs in corneal regeneration. In essence, this review not only elucidates the current state of corneal treatments and tissue engineering but also outlines regulatory pathways and anticipates the transformative impact of artificial intelligence, providing a comprehensive guide for researchers, practitioners, and policymakers in the field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cancer pain seriously reduces the quality of life of cancer patients. However, most research about cancer focuses solely on inhibiting tumor growth, neglecting the issue of cancer pain. Therefore, the development of therapeutic agents with both tumor suppression and cancer pain relief is crucial to achieve human-centered treatment. Here, the work reports curcumin (CUR) and ropivacaine (Ropi) coincorporating CaCO 3 /PDA nanoparticles (CaPNM CUR+Ropi ) that realized efficient tumor immunotherapy and cancer pain suppression. The therapeutic efficiency and mechanism are revealed in vitro and in vivo. The results indicate that CaPNM CUR+Ropi underwent tumor microenvironment-responsive degradation and realized rapid release of calcium ions, Ropi, and CUR. The excessive intracellular calcium triggered the apoptosis of tumor cells, and the transient pain caused by the tumor injection was relieved by Ropi. Simultaneously, CUR reduced the levels of immunosuppressive factor (TGF-β) and inflammatory factor (IL-6, IL-1β, and TNF-α) in the tumor microenvironment, thereby continuously augmenting the immune response and alleviating inflammatory pain of cancer animals. Meanwhile, the decrease of TGF-β leads to the reduction of transient receptor potential vanilloid 1 (TRPV1) expression, thereby alleviating hyperalgesia and achieving long-lasting analgesic effects. The design of the nanosystem provides a novel idea for human-centered tumor treatment in the future.

Drug adherence is a significant medical issue, often responsible for sub-optimal outcomes during the treatment of chronic diseases such as rheumatoid or psoriatic arthritis. Monoclonal antibodies (which are exclusively given parenterally) have been proven to be an effective treatment in these cases. The use of auto-injectors is an effective strategy to improve drug adherence in parenteral treatments since these pen-like devices offer less discomfort and increased user-friendliness over conventional syringe-based delivery. This study aims to investigate the feasibility of including a monoclonal antibody as a solid formulation inside an auto-injector pen. Specifically, the objective was to evaluate the drug stability after a concentration (to reduce the amount of solvent and space needed) and freeze-drying procedure. A preliminary screening of excipients to improve stability was also performed. The nano-DSC results showed that mannitol improved the stability of the concentrated, freeze-dried antibody in comparison to its counterpart without it. However, a small instability of the C H 2 domain was still found for mannitol samples, which will warrant further investigation. The present results serve as a stepping stone towards advancing future drug delivery systems that will ultimately improve the patient experience and associated drug adherence.

Collagen is a cornerstone protein for tissue engineering and 3D bioprinting due to its outstanding biocompatibility, low immunogenicity, and natural abundance in human tissues. Nonetheless, it still poses some important challenges, such as complicated and limited extraction processes, usually accompanied by batch- to-batch reproducibility and influence of factors, such as temperature, pH, and ionic strength. In this work, we evaluated the suitability and performance of new, fibrillar type I collagen as standardized and reproducible collagen source for 3D printing and bioprinting. The acidic, native fibrous collagen formulation (5% w/w) performed remarkably during 3D printing, which was possible to print constructs of up to 27 layers without collapsing. On the other hand, the fibrous collagen mass has been modified to provide a fast, reliable, and easily neutralizable process. The neutralization with TRIS-HCl enabled the inclusion of cells without hindering printability. The cell-laden constructs were printed under mild conditions (50-80 kPa, pneumatic 3D printing), providing remarkable cellular viability (>90%) as well as a stable platform for cell growth and proliferation in vitro . Therefore, the native, type I collagen masses characterized in this work offer a reproducible and reliable source of collagen for 3D printing and bioprinting purposes., Competing Interests: Authors Amaia Guembe, José M. Rey, Teresa Zúñiga, Jesús M. Izco and José I. Recalde declare that they work for the company Viscofan, while the rest declare no conflicts of interest., (Copyright:© 2023, Garcia-Villen F, Guembe A, Rey JM, et al.)

Vascular stents (VS) have revolutionized the treatment of cardiovascular diseases, as evidenced by the fact that the implantation of VS in coronary artery disease (CAD) patients has become a routine, easily approachable surgical intervention for the treatment of stenosed blood vessels. Despite the evolution of VS throughout the years, more efficient approaches are still required to address the medical and scientific challenges, especially when it comes to peripheral artery disease (PAD). In this regard, three-dimensional (3D) printing is envisaged as a promising alternative to upgrade VS by optimizing the shape, dimensions and stent backbone (crucial for optimal mechanical properties), making them customizable for each patient and each stenosed lesion. Moreover, the combination of 3D printing with other methods could also upgrade the final device. This review focuses on the most recent studies using 3D printing techniques to produce VS, both by itself and in combination with other techniques. The final aim is to provide an overview of the possibilities and limitations of 3D printing in the manufacturing of VS. Furthermore, the current situation of CAD and PAD pathologies is also addressed, thus highlighting the main weaknesses of the already existing VS and identifying research gaps, possible market niches and future directions., Competing Interests: The authors declare no conflicts of interests., (Copyright: © 2023, Garcia-Villen, et al.)

Bone tissue is usually damaged after big traumas, tumors, and increasing aging-related diseases such as osteoporosis and osteoarthritis. Current treatments are based on implanting grafts, which are shown to have several inconveniences. In this regard, tissue engineering through the 3D bioprinting technique has arisen to manufacture structures that would be a feasible therapeutic option for bone regenerative medicine. In this study, nanocellulose-alginate (NC-Alg)-based bioink is improved by adding two different inorganic components such as hydroxyapatite (HAP) and graphene oxide (GO). First, ink rheological properties and biocompatibility are evaluated as well as the influence of the sterilization process on them. Then, scaffolds are characterized. Finally, biological studies of embedded murine D1 mesenchymal stem cells engineered to secrete erythropoietin are performed. Results show that the addition of both HAP and GO prevents NC-Alg ink from viscosity lost in the sterilization process. However, GO is reduced due to short cycle autoclave sterilization, making it incompatible with this ink. In addition, HAP and GO have different influences on scaffold architecture and surface as well as in swelling capacity. Scaffolds mechanics, as well as cell viability and functionality, are promoted by both elements addition. Additionally, GO demonstrates an enhanced bone differentiation capacity., (© 2022 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

In the last few years, attempts to improve the regeneration of damaged tendons have been rising due to the growing demand. However, current treatments to restore the original performance of the tissue focus on the usage of grafts; although, actual grafts are deficient because they often cannot provide enough support for tissue regeneration, leading to additional complications. The beneficial effect of combining 3D bioprinting and dECM as a novel bioink biomaterial has recently been described. Tendon dECMs have been obtained by using either chemical, biological, or/and physical treatments. Although decellularization protocols are not yet standardized, recently, different protocols have been published. New therapeutic approaches embrace the use of dECM in bioinks for 3D bioprinting, as it has shown promising results in mimicking the composition and the structure of the tissue. However, major obstacles include the poor structural integrity and slow gelation properties of dECM bioinks. Moreover, printing parameters such as speed and temperature have to be optimized for each dECM bioink. Here, we show that dECM bioink for 3D bioprinting provides a promising approach for tendon regeneration for future clinical applications.

Osteochondral injuries can lead to osteoarthritis (OA). OA is characterized by the progressive degradation of the cartilage tissue together with bone tissue turnover. Consequently, joint pain, inflammation, and stiffness are common, with joint immobility and dysfunction being the most severe symptoms. The increase in the age of the population, along with the increase in risk factors such as obesity, has led OA to the forefront of disabling diseases. In addition, it not only has an increasing prevalence, but is also an economic burden for health systems. Current treatments are focused on relieving pain and inflammation, but they become ineffective as the disease progresses. Therefore, new therapeutic approaches, such as tissue engineering and 3D bioprinting, have emerged. In this review, the advantages of using 3D bioprinting techniques for osteochondral regeneration are described. Furthermore, the biomaterials, cell types, and active molecules that are commonly used for these purposes are indicated. Finally, the most recent promising results for the regeneration of cartilage, bone, and/or the osteochondral unit through 3D bioprinting technologies are considered, as this could be a feasible therapeutic approach to the treatment of OA.

Cartilage is a connective tissue which a limited capacity for healing and repairing. In this context, osteoarthritis (OA) disease may be developed with high prevalence in which the use of scaffolds may be a promising treatment. In addition, three-dimensional (3D) bioprinting has become an emerging additive manufacturing technology because of its rapid prototyping capacity and the possibility of creating complex structures. This study is focused on the development of nanocellulose-alginate (NC-Alg) based bioinks for 3D bioprinting for cartilage regeneration to which it is added chondroitin sulfate (CS) and dermatan sulfate (DS). First, rheological properties are evaluated. Then, sterilization effect, biocompatibility, and printability on developed NC-Alg-CS and NC-Alg-DS inks are evaluated. Subsequently, printed scaffolds are characterized. Finally, NC-Alg-CS and NC-Alg-DS inks are loaded with murine D1-MSCs-EPO and cell viability and functionality, as well as the chondrogenic differentiation ability are assessed. Results show that the addition of both CS and DS to the NC-Alg ink improves its characteristics in terms of rheology and cell viability and functionality. Moreover, differentiation to cartilage is promoted on NC-Alg-CS and NC-Alg-DS scaffolds. Therefore, the utilization of MSCs containing NC-Alg-CS and NC-Alg-DS scaffolds may become a feasible tissue engineering approach for cartilage regeneration., (© 2022 Wiley-VCH GmbH.)

The adaptation and progress of 3D printing technology toward 3D bioprinting (specifically adapted to biomedical purposes) has opened the door to a world of new opportunities and possibilities in tissue engineering and regenerative medicine. In this regard, 3D bioprinting allows for the production of tailor-made constructs and organs as well as the production of custom implants and medical devices. As it is a growing field of study, currently, the attention is heeded on the optimization and improvement of the mechanical and biological properties of the so-called bioinks/biomaterial inks. One of the strategies proposed is the use of inorganic ingredients (clays, hydroxyapatite, graphene, carbon nanotubes and other silicate nanoparticles). Clays have proven to be useful as rheological and mechanical reinforcement in a wide range of fields, from the building industry to pharmacy. Moreover, they are naturally occurring materials with recognized biocompatibility and bioactivity, revealing them as optimal candidates for this cutting-edge technology. This review deals with the use of clays (both natural and synthetic) for tissue engineering and regenerative medicine through 3D printing and bioprinting. Despite the limited number of studies, it is possible to conclude that clays play a fundamental role in the formulation and optimization of bioinks and biomaterial inks since they are able to improve their rheology and mechanical properties, thus improving printability and construct resistance. Additionally, they have also proven to be exceptionally functional ingredients (enhancing cellular proliferation, adhesion, differentiation and alignment), controlling biodegradation and carrying/releasing actives with tissue regeneration therapeutic activities.

Tendon injuries are a global health problem that affects millions of people annually. The properties of tendons make their natural rehabilitation a very complex and long-lasting process. Thanks to the development of the fields of biomaterials, bioengineering and cell biology, a new discipline has emerged, tissue engineering. Within this discipline, diverse approaches have been proposed. The obtained results turn out to be promising, as increasingly more complex and natural tendon-like structures are obtained. In this review, the nature of the tendon and the conventional treatments that have been applied so far are underlined. Then, a comparison between the different tendon tissue engineering approaches that have been proposed to date is made, focusing on each of the elements necessary to obtain the structures that allow adequate regeneration of the tendon: growth factors, cells, scaffolds and techniques for scaffold development. The analysis of all these aspects allows understanding, in a global way, the effect that each element used in the regeneration of the tendon has and, thus, clarify the possible future approaches by making new combinations of materials, designs, cells and bioactive molecules to achieve a personalized regeneration of a functional tendon., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Three-dimensional (3D) printing is a game changer technology that holds great promise for a wide variety of biomedical applications, including ophthalmology. Through this emerging technique, specific eye tissues can be custom-fabricated in a flexible and automated way, incorporating different cell types and biomaterials in precise anatomical 3D geometries. However, and despite the great progress and possibilities generated in recent years, there are still challenges to overcome that jeopardize its clinical application in regular practice. The main goal of this review is to provide an in-depth understanding of the current status and implementation of 3D bioprinting technology in the ophthalmology field in order to manufacture relevant tissues such as cornea, retina and conjunctiva. Special attention is paid to the description of the most commonly employed bioprinting methods, and the most relevant eye tissue engineering studies performed by 3D bioprinting technology at preclinical level. In addition, other relevant issues related to use of 3D bioprinting for ocular drug delivery, as well as both ethical and regulatory aspects, are analyzed. Through this review, we aim to raise awareness among the research community and report recent advances and future directions in order to apply this advanced therapy in the eye tissue regeneration field., Competing Interests: The authors declare no conflict of interest.

Background: Chronic heart failure (CHF) reduces quality of life and causes hospitalisation and death. Identifying predictive factors of such events may help change the natural history of this condition., Aim: To develop and validate a stratification system for classifying patients with CHF, according to their degree of disability and need for hospitalisation due to any unscheduled cause, over a period of 1 year., Methods and Analysis: Prospective, concurrent, cohort-type study in two towns in the Madrid autonomous region having a combined population of 1 32 851. The study will include patients aged over 18 years who meet the following diagnostic criteria: symptoms and typical signs of CHF (Framingham criteria) and left ventricular ejection fraction (EF)<50% or structural cardiac lesion and/or diastolic dysfunction in the presence of preserved EF (EF>50%).Outcome variables will be(a) Disability, as measured by the WHO Disability Assessment Schedule V.2.0 Questionnaire, and (b) unscheduled hospitalisations. The estimated sample size is 557 patients, 371 for predictive model development (development cohort) and 186 for validation purposes (validation cohort). Predictive models of disability or hospitalisation will be constructed using logistic regression techniques. The resulting model(s) will be validated by estimating the probability of outcomes of interest for each individual included in the validation cohort., Ethics and Dissemination: The study protocol has been approved by the Clinical Research Ethics Committee of La Princesa University Teaching Hospital (PI-705). All results will be published in a peer-reviewed journal and shared with the medical community at conferences and scientific meetings., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)