The incidence of diabetes mellitus (DM) is steadily increasing annually, with 537 million diabetic patients as of 2021. Restoring diminished β cell mass or impaired islet function is crucial in treating DM, particularly type 1 DM. However, the regenerative capacity of islet β cells, which primarily produce insulin, is severely limited, and natural regeneration is only observed in young rodents or children. Hence, there is an urgent need to develop advanced therapeutic approaches that can regenerate endogenous β cells or replace them with stem cell (SC)-derived or engineered β-like cells. Current strategies for treating insulin-dependent DM mainly include promoting the self-replication of endogenous β cells, inducing SC differentiation, reprogramming non-β cells into β-like cells, and generating pancreatic-like organoids through cell-based intervention. In this Review, we discuss the current state of the art in these approaches, describe associated challenges, propose potential solutions, and highlight ongoing efforts to optimize β cell or islet transplantation and related clinical trials. These effective cell-based therapies will generate a sustainable source of functional β cells for transplantation and lay strong foundations for future curative treatments for DM.

In the realm of dental tissue regeneration research, various constraints exist such as the potential variance in cell quality, potency arising from differences in donor tissue and tissue microenvironment, the difficulties associated with sustaining long-term and large-scale cell expansion while preserving stemness and therapeutic attributes, as well as the need for extensive investigation into the enduring safety and effectiveness in clinical settings. The adoption of artificial intelligence (AI) technologies has been suggested as a means to tackle these challenges. This is because, tissue regeneration research could be advanced through the use of diagnostic systems that incorporate mining methods such as neural networks (NN), fuzzy, predictive modeling, genetic algorithms, machine learning (ML), cluster analysis, and decision trees. This article seeks to offer foundational insights into a subset of AI referred to as artificial neural networks (ANNs) and assess their potential applications as essential decision-making support tools in the field of dentistry, with a particular focus on tissue engineering research. Although ANNs may initially appear complex and resource intensive, they have proven to be effective in laboratory and therapeutic settings. This expert system can be trained using clinical data alone, enabling their deployment in situations where rule-based decision-making is impractical. As ANNs progress further, it is likely to play a significant role in revolutionizing dental tissue regeneration research, providing promising results in streamlining dental procedures and improving patient outcomes in the clinical setting.

Autologous fat grafting has been widely adopted in cosmetic and reconstructive procedures recently. With the emerging of negative-pressure-assisted liposuction system, the harvesting process of fat grafting is more standardized, controllable, and efficient. Each component in the system could influence the biomechanical environment of lipoaspirate. Several reviews have studied the impact of negative pressure on fat regeneration. As the initial part of the harvesting system, cannulas possess their unique mechanical parameters and their influence on lipoaspirate biomechanical characters, biological behaviors, and regeneration patterns remains unclear. Basic and studies have been performed to determine the possible mechanisms. Instant studies focus on adipocytes, stromal vascular fraction cells, fat particles, and growth factors, while grafting experiments analyze the graft retention rate and histology. Understanding the different regeneration patterns of lipoaspirate and the mechanisms behind may facilitate the choice of harvesting cannulas in clinical practice.

Nasal cartilage serves a crucial structural function for the nose, where rebuilding the cartilaginous framework is an essential aspect of nasal reconstruction. Conventional methods of nasal reconstruction rely on autologous cartilage harvested from patients, which contributes to donor site pain and the potential for site-specific complications. Some patients are not ideal candidates for this procedure due to a lack of adequate substitute cartilage due to age-related calcification, differences in tissue quality, or due to prior surgeries. Tissue engineering, combined with three-dimensional printing technologies, has emerged as a promising method of generating biomimetic tissues to circumvent these issues to restore normal function and aesthetics. We conducted a comprehensive literature review to examine the applications of three-dimensional printing in conjunction with tissue engineering for the generation of nasal cartilage grafts. This review aims to compare various approaches and discuss critical considerations in the design of these grafts.

Cartilage plays an important role in supporting soft tissues, reducing joint friction, and distributing pressure. However, its self-repair capacity is limited due to the lack of blood vessels, nerves, and lymphatic systems. Tissue engineering offers a potential solution to promote cartilage regeneration by combining scaffolds, seed cells, and growth factors. Among these, growth factors play a critical role in regulating cell proliferation, differentiation, and extracellular matrix remodeling. However, their instability, susceptibility to degradation and potential side effects limit their effectiveness. This article reviews the main growth factors used in cartilage tissue engineering and their delivery strategies, including affinity-based delivery, carrier-assisted delivery, stimuli-responsive delivery, spatial structure-based delivery, and cell system-based delivery. Each method shows unique advantages in enhancing the delivery efficiency and specificity of growth factors but also faces challenges such as cost, biocompatibility, and safety. Future research needs to further optimize these strategies to achieve more efficient, safe, and economical delivery of growth factors, thereby advancing the clinical application of cartilage tissue engineering.

Three-dimensional (3D) tissue-engineered models are under investigation to recapitulate tissue architecture and functionality, thereby overcoming limitations of traditional two-dimensional cultures and preclinical animal models. This review highlights recent developments in 3D platforms designed to model diseases that affect numerous tissues and organs, including cardiovascular, gastrointestinal, bone marrow, neural, reproductive, and pulmonary systems. We discuss current technologies for engineered tissue models, highlighting the advantages, limitations, and important considerations for modeling tissues and diseases. Lastly, we discuss future advancements necessary to enhance the reliability of 3D models of tissue development and disease.

Articular cartilage is crucial in human physiology, and its degeneration poses a significant public health challenge. While recent advancements in 3D bioprinting and tissue engineering show promise for cartilage regeneration, there remains a gap between research findings and clinical application. This review critically examines the mechanical and biological properties of hyaline cartilage, along with current 3D manufacturing methods and analysis techniques. Moreover, we provide a quantitative synthesis of bioink properties used in cartilage tissue engineering. After screening 181 initial works, 33 studies using extrusion bioprinting were analyzed and synthesized, presenting results that indicate the main materials, cells, and methods utilized for mechanical and biological evaluation. Altogether, this review motivates the standardization of mechanical analyses and biomaterial assessments of 3D bioprinted constructs to clarify their chondrogenic potential.

Amniotic membrane transplantation is commonly employed in ophthalmology to mend corneal epithelial and stromal defects. Its effectiveness in restoring the ocular surface has been widely acknowledged in clinical practice. Nevertheless, there is ongoing debate regarding the comparative effectiveness of using fresh amniotic membranes versus preserved ones. The objective of this meta-analysis was to ascertain whether there is a disparity in the effectiveness of fresh versus preserved amniotic membrane in the restoration of the ocular surface in clinical practice. The study utilized the following keywords: "fresh amniotic membrane," "preserved amniotic membrane," "amniotic membrane transplantation," and "ocular surface reconstruction." The study conducted a comprehensive search for relevant studies published until April 18, 2024. Seven different databases, namely PubMed, Web of Science, Embase, Cochrane, China Knowledge, China Science and Technology Journal VIP database, and Wanfang database, were utilized. The search was performed using the keywords "fresh amniotic membrane," "preserved amniotic membrane," "amniotic membrane transplantation," and "ocular surface reconstruction." The process of literature review and data extraction was carried out separately by two researchers, and all statistical analyses were conducted using Review Manager 5.4.1. The final analysis comprised nine cohort studies, encompassing a total of 408 participants. The statistics included six outcome indicators: visual acuity (relative risk [RR] = 1.07, 95% confidence interval [CI] = 0.93-1.24, = 0); amniotic membrane viability (RR = 1.00, 95% CI = 0.93-1.08, = 0); ocular congestion resolution (RR = 1.11, 95% CI = 0.97-1.26, = 0); fluorescent staining of amniotic membranes on the second day after the operation (RR = 1.31, 95% CI = 0.80-2.14, = 11); postoperative recurrence rate (RR = 1.01, 95% CI = 0.50-2.03, = 0); and premature lysis of amniotic membrane implants (RR = 0.96, 95% CI = 0.49-1.88, = 0). The findings indicated that there was no statistically significant disparity between fresh and preserved amniotic membranes across any of the measured variables. There is no substantial disparity in the effectiveness of fresh and preserved amniotic membrane transplants in restoring the ocular surface, and both yield favorable and consistent outcomes.

Human vocal folds (VFs), a pair of small, soft tissues in the larynx, have a layered mucosal structure with unique mechanical strength to support high-level tissue deformation by phonation. Severe pathological changes to VF have causes including surgery, trauma, age-related atrophy, and radiation, and lead to partial or complete communication loss and difficulty in breathing and swallowing. VF glottal insufficiency requires injectable VF biomaterials such as hyaluronan, calcium hydroxyapatite, and autologous fat to augment VF functions. Although these biomaterials provide an effective short-term solution, significant variations in patient response and requirements of repeat reinjection remain notable challenges in clinical practice. Tissue engineering strategies have been actively explored in the search of an injectable biomaterial that possesses the capacity to match native tissue's material properties while promoting permanent tissue regeneration. This review aims to assess the current status of biomaterial development in VF tissue engineering. The focus will be on examining state-of-the-art techniques including modification with bioactive molecules, cell encapsulation, composite materials, and crosslinking with click chemistry. We will discuss potential opportunities that can further leverage these engineering techniques in the advancement of VF injectable biomaterials. Impact Statement Injectable vocal fold (VF) biomaterials augment tissue function through minimally invasive procedures, yet there remains a need for long-term VF reparation. This article reviews cutting-edge research in VF biomaterial development to propose safe and effective tissue engineering strategies for improving regenerative outcomes. Special focus is paid to methods to enhance bioactivity and achieve tissue-mimicking mechanical properties, longer stability, and inherent biomaterial bioactivity.

Articular cartilage is crucial in human physiology, and its degeneration poses a significant public health challenge. While recent advancements in 3D bioprinting and tissue engineering show promise for cartilage regeneration, there remains a gap between research findings and clinical application. This review critically examines the mechanical and biological properties of hyaline cartilage, along with current 3D manufacturing methods and analysis techniques. Moreover, we provide a quantitative synthesis of bioink properties used in cartilage tissue engineering. After screening 181 initial works, 33 studies using extrusion bioprinting were analyzed and synthesized, presenting results that indicate the main materials, cells, and methods utilized for mechanical and biological evaluation. Altogether, this review motivates the standardization of mechanical analyses and biomaterial assessments of 3D bioprinted constructs to clarify their chondrogenic potential.

Arterial stenosis caused by atherosclerosis often requires stent implantation to increase the patency of target artery. However, such external devices often lead to in-stent restenosis due to inadequate re-endothelialization and subsequent inflammatory responses. Therefore, re-endothelialization strategies after stent implantation have been developed to enhance endothelial cell recruitment or to capture circulating endothelial progenitor cells. Notably, recent research indicates that coating stent surfaces with biogenic materials enhances the long-term safety of implantation, markedly diminishing the risk of in-stent restenosis. In this review, we begin by describing the pathophysiology of coronary artery disease and in-stent restenosis. Then, we review the characteristics and materials of existing stents used in clinical practice. Lastly, we explore biogenic materials aimed at accelerating re-endothelialization, including extracellular matrix, cells, and extracellular vesicles. This review helps overcome the limitations of current stents for cardiovascular disease and outlines the next phase of research and development.

This research is dedicated to uncovering the evolving trends, progressive developments, and principal research themes in tissue engineering and regenerative medicine for rotator cuff injuries, which spans the past two decades. This article leverages visualization methodology to provide a clear and comprehensive portrayal of the dynamic landscape within the field. We compiled 758 research entries centered on the application of tissue engineering and regenerative medicine in treating rotator cuff injuries, drawing from the Web of Science Core Collection database and covering the period from 2003 to 2023. Analytical tools such as VOSviewer, CiteSpace, and GraphPad Prism were used. We conducted comprehensive analyses to discern the general characteristics, historical evolution, key literature, and pivotal keywords within this research field. This comprehensive analysis enabled us to identify emerging focal points and current trends in the application of tissue engineering and regenerative medicine for addressing rotator cuff injuries. The compilation of 758 articles in this study indicates a consistent upward trajectory in publications concerning tissue engineering and regenerative medicine for rotator cuff injuries. The scholarly contributions from the United States, China, and South Korea have notable influence on the progression of this research area. The analysis delineated ten specific research subdomains, including fatty infiltration, tears, tissue engineering, shoulder pain, tendon repair, extracellular matrix (ECM), and platelet-rich plasma growth factors. Noteworthy is the recurrent mention of keywords such as "mesenchymal stem cells," "repair," and "platelet-rich plasma" throughout past two decades, highlighting their critical role in the evolution of the relevant field. This bibliometric analysis meticulously examines 758 publications, offering an in-depth exploration of the developments in tissue engineering and regenerative medicine for rotator cuff injuries between 2003 and 2023. The study effectively constructs a knowledge map, delineating the progressive contours of research in this domain. By pinpointing prevailing trends and emerging hotspots, the study furnishes crucial insights, setting a direction for forthcoming explorations and providing guidance for future researchers in this evolving field.

Solid tumors represent the most common type of cancer in humans and are classified into sarcomas, lymphomas, and carcinomas based on the originating cells. Among these, carcinomas, which arise from epithelial and glandular cells lining the body's tissues, are the most prevalent. Around the world, a significant increase in the incidence of solid tumors is observed during recent years. In this context, efforts to discover more effective cancer treatments have led to a deeper understanding of the tumor microenvironment (TME) and its components. Currently, the interactions between cancer cells and elements of the TME are being intensely investigated. Remarkable progress in research is noted, largely owing to the development of advanced models, such as tumor-on-a-chip models that assist in understanding and ultimately discovering new effective treatments for a specific type of cancer. The purpose of this article is to provide a review of the TME and cancer cell components, along with the advances on tumor-on-a-chip models designed to mimic tumors, offering a perspective on the current state of the art. Recent studies using this kind of microdevices that reproduce the TME have allowed a better understanding of the cancer and its treatments. Nevertheless, current applications of this technology present some limitations that must be overcome to achieve a broad application by researchers looking for a deeper knowledge of cancer and new strategies to improve current therapies.

Bone defects because of age, trauma, and surgery, which are exacerbated by medication side effects and common diseases such as osteoporosis, diabetes, and rheumatoid arthritis, are a problem of epidemic scale. The present clinical standard for treating these defects includes autografts and allografts. Although both treatments can promote robust regenerative outcomes, they fail to strike a desirable balance of availability, side effect profile, consistent regenerative efficacy, and affordability. This difficulty has contributed to the rise of bone tissue engineering (BTE) as a potential avenue through which enhanced bone regeneration could be delivered. BTE is founded upon a paradigm of using biomaterials, bioactive factors, osteoblast lineage cells (ObLCs), and vascularization to cue deficient bone tissue into a state of regeneration. Despite promising preclinical results, BTE has had modest success in being translated into the clinical setting. One barrier has been the simplicity of its paradigm relative to the complexity of biological bone. Therefore, this paradigm must be critically examined and expanded to better account for this complexity. One potential avenue for this is a more detailed consideration of osteoclast lineage cells (OcLCs). Although these cells ostensibly oppose ObLCs and bone regeneration through their resorptive functions, a myriad of investigations have shed light on their potential to influence bone equilibrium in more complex ways through their interactions with both ObLCs and bone matrix. Most BTE research has not systematically evaluated their influence. Yet contrary to expectations associated with the paradigm, a selection of BTE investigations has demonstrated that this influence can enhance bone regeneration in certain contexts. In addition, much work has elucidated the role of many controllable scaffold parameters in both inhibiting and stimulating the activity of OcLCs in parallel to bone regeneration. Therefore, this review aims to detail and explore the implications of OcLCs in BTE and how they can be leveraged to improve upon the existing BTE paradigm.

There is a critical need for novel approaches to translate cell therapy and regenerative medicine to clinical practice. Magnetic cell targeting with site specificity has started to open avenues in these fields as a potential therapeutic platform. Magnetic targeting is gaining popularity in the field of biomedicine due to its ability to concentrate and retain at a target site while minimizing deleterious effects at off-target sites. It is regarded as a relatively straightforward and safe approach for a wide range of therapeutic applications. This review discusses the latest advancements and approaches in magnetic cell targeting using endocytosed and surface-bound magnetic nanoparticles as well as tracking using magnetic resonance imaging (MRI). The most common form of magnetic nanoparticles is superparamagnetic iron oxide nanoparticles (SPION). The biodegradable and biocompatible properties of these magnetically responsive particles and capacity for rapid endocytosis into cells make them a breakthrough in targeted therapy. This review further discusses specific applications of magnetic targeting approaches in cardiovascular tissue engineering including myocardial regeneration, therapeutic angiogenesis, and endothelialization of implantable cardiovascular devices.

Meniscal damage is one of the prevalent causes of knee pain, swelling, instability, and functional compromise, frequently culminating in osteoarthritis (OA). Timely and appropriate interventions are crucial to relieve symptoms and prevent or delay the onset of OA. Contemporary surgical treatments include total or partial meniscectomy, meniscal repair, allograft meniscal transplantation, and synthetic meniscal implants, but each presents its specific limitations. Recently, regenerative medicine and tissue engineering have emerged as promising fields, offering innovative prospects for meniscal regeneration and repair. This review delineates current surgical methods, elucidating their specific indications, advantages, and disadvantages. Concurrently, it delves into state-of-the-art tissue engineering techniques aimed at the functional regenerative repair of meniscus. Recommendations for future research and clinical practice are also provided.

The dura mater, the furthest and strongest layer of the meninges, is crucial for protecting the brain and spinal cord. Its biomechanical behavior is vital, as any alterations can compromise biological functions. In recent decades, interest in the dura mater has increased due to the need for hermetic closure of dural defects prompting the development of several substitutes. Collagen-based dural substitutes are common commercial options, but they lack the complex biological and structural elements of the native dura mater, impacting regeneration and potentially causing complications like wound/postoperative infection and cerebrospinal fluid (CSF) leakage. To face this issue, recent tissue engineering approaches focus on creating biomimetic dura mater substitutes. The objective of this review is to discuss whether mimicking the mechanical properties of native tissue or ensuring high biocompatibility and bioactivity is more critical in developing effective dural substitutes, or if both aspects should be systematically linked. After a brief description of the properties and architecture of the native cranial dura, we describe the advantages and limitations of biomimetic dura mater substitutes to better understand their relevance. In particular, we consider biomechanical properties' impact on dura repair's effectiveness. Finally, the obstacles and perspectives for developing the ideal dural substitute are explored.

Impact Statement The current article examines urethral reconstruction on three fronts: presently available grafts, clinical trials, and preclinical studies. In this context, studies have focused on various types of biomaterial grafts, including natural, synthetic, and decellularized, combined with or without cells or growth factors, aiming to improve outcomes at both clinical and pre-clinical stages. Subsequently, four stages in the commercialization regulatory pathway in urethra engineering were examined, focusing on the commercialization challenges, particularly those associated with urethral products. Finally, the forthcoming challenges in urethra engineering and potential solutions for its enhancement have been explored. [Figure: see text].

Cartilage tissue, encompassing hyaline cartilage, fibrocartilage, and elastic cartilage, plays a pivotal role in the human body because of its unique composition, structure, and biomechanical properties. However, the inherent avascularity and limited regenerative capacity of cartilage present significant challenges to its healing following injury. This review provides a comprehensive analysis of the current state of cartilage tissue engineering, focusing on the critical components of cell sources, scaffolds, and growth factors tailored to the regeneration of each cartilage type. We explore the similarities and differences in the composition, structure, and biomechanical properties of the three cartilage types and their implications for tissue engineering. A significant emphasis is placed on innovative strategies for cartilage regeneration, including the potential for transformation of cartilage types through microenvironmental manipulation, which may offer novel avenues for repair and rehabilitation. The review underscores the necessity of a nuanced approach to cartilage tissue engineering, recognizing the distinct requirements of each cartilage type while exploring the potential of transforming one cartilage type into another as a flexible and adaptive repair strategy. Through this detailed examination, we aim to broaden the understanding of cartilage tissue engineering and inspire further research and development in this promising field.

Vascular surgery faces a critical demand for novel vascular grafts that are biocompatible and thromboresistant. This urgency particularly applies to bypass operations involving small caliber vessels. In the realm of tissue engineering, the development of fully vascularized organs holds great promise as a solution to organ shortage for transplantation. To achieve this, it is imperative to (re-)construct a biocompatible and non-thrombogenic vascular network within these organs. In this systematic review, we identify, classify and discuss basic principles and methods used to perform in vitro/ex vivo dynamic thrombogenicity testing of perfusable tissue engineered organs and tissues. We conducted a pre-registered systematic review of studies published in the last 23 years according to PRISMA-P Guidelines, comprising a systematic data extraction, in-depth analysis and risk of bias assessment of 116 included studies. We identified shaking (n=28), flow loop (n=17), ex vivo (arterio-venous shunt, n=33) and dynamic in vitro models (n=38) as main approaches for thrombogenicity assessment. This comprehensive review unveils a prevalent lack of standardization and serves as a valuable guide in the design of standardized experimental setups.

Peripheral nerve regeneration after trauma poses a substantial clinical challenge that has already been investigated for many years. Infiltration of immune cells is a critical step in the response to nerve damage that creates a supportive microenvironment for regeneration. In this work, we focus on a special type of immune cell, macrophage, in addressing the problem of neuronal regeneration. We discuss the complex endogenous mechanisms of peripheral nerve injury and regrowth vis-à-vis macrophages, including their recruitment, polarization, and interplay with Schwann cells post-trauma. Furthermore, we elucidate the underlying mechanisms by which exogenous stimuli govern the above events. Finally, we summarize the necessary roles of macrophages in peripheral nerve lesions and reconstruction. There are many challenges in controlling macrophage functions to achieve complete neuronal regeneration, even though considerable progress has been made in understanding the connection between these cells and peripheral nerve damage.