Tissue Engineering. Part B, Reviews最新文献

Repair of the tendon-bone interface (TBI) remains a significant clinical challenge due to its complex biomechanical environment and hierarchical structure. Conventional surgical approaches often fail to fully reestablish native tissue architecture and function. In recent years, tissue engineering strategies have increasingly emphasized the application of mesenchymal stem cells (MSCs) and platelet-derived products to promote regeneration. MSCs possess multilineage differentiation potential and immunomodulatory capabilities, making them attractive candidates for TBI repair. Platelets, through their rich secretome, orchestrate essential regenerative processes such as cell recruitment, angiogenesis, and immune modulation. This review explores the molecular crosstalk between MSCs and platelets, critically examines current approaches utilizing platelet-rich plasma (PRP)-MSC combinations and platelet-derived exosome therapies and underscores the urgent need for standardization to optimize therapeutic outcomes in PRP-MSC-based regenerative strategies.

Neurological disorders such as Alzheimer's disease, Parkinson's disease, and stroke pose significant challenges for conventional therapy due to the complexities of the blood-brain barrier (BBB) and the restricted delivery of drugs to the central nervous system. Exosomes, a type of small extracellular vesicle secreted by nearly all cell types, hold substantial promise as delivery vehicles for therapeutic agents in treating these conditions. Notably, stem cell-secreted exosomes have emerged as particularly effective due to their regenerative potential and natural ability to cross the BBB. Similarly, hydrogels have gained recognition as versatile biomaterials capable of supporting sustained release and targeted delivery of therapeutics. The combination of the regenerative properties of stem cell-derived exosomes (SC-Exos) with the structural and functional benefits of hydrogels offers a promising approach for enhancing neurogenesis, modulating neuroinflammation, and facilitating tissue repair. This review explores the origin, structure, and modifications of exosomes as well as the synthesis and incorporation methods of hydrogels in the therapeutic context for debilitating neurological disorders. It highlights recent advancements in using SC-Exos and hydrogels for therapeutic delivery, addressing both current challenges and future applications. Improving our understanding of hydrogels loaded with SC-Exos for cargo transportation and neural tissue regeneration may pave the way for novel therapeutic strategies.

Platelet-rich plasma (PRP) is a blood product with higher platelet concentrations than whole blood, offering controlled delivery of growth factors (GFs) for regenerative medicine. PRP plays pivotal roles in tissue restoration mechanisms, including angiogenesis, fibroblast proliferation, and extracellular matrix development, making it applicable across various regenerative medicine treatments. Despite promising results in different tissue injuries, challenges such as short half-life and rapid deactivation by proteases persist. To address these challenges, biomaterial-based delivery scaffolds, such as sponges or hydrogels, have been investigated. Current studies exhibit that PRP-loaded scaffolds fix these issues due to the sustained release of GFs. In this regard, given the widespread application of PRP in clinical studies, the use of PRP-loaded scaffolds has drawn significant consideration in tissue engineering (TE). Therefore, this review briefly introduces PRP as a rich origin of GFs, its classification, and preparation methods and discusses PRP applications in regenerative medicine. This study also emphasizes and reviews the latest research on the using scaffolds for PRP delivery in diverse fields of TE, including skin, bone, and cartilage repair.

Electric fields (EFs) offer a powerful tool for manipulating cells and modulating their behavior, holding significant promise for regenerative medicine and cell biology. We provide a comprehensive overview of the effects of different types of EF on eukaryotic cells with the special focus on physical mechanisms and signaling pathways involved. Direct current EF induces electrophoresis and electroosmosis, influencing cell migration, proliferation, and differentiation. Alternating current EF, through dielectric polarization and dielectrophoresis, enables cell manipulation, trapping, and sorting. Pulsed EF, particularly high-intensity, short-duration pulses, induces reversible and irreversible electroporation, facilitating drug and gene delivery. The review covers some technological aspects of EF generation, emphasizing the importance of experimental setups, and integration with microfluidic platforms for high-throughput analysis and precise manipulations. Furthermore, the synergistic potential of combining EFs with optical tweezers is highlighted, enabling fine-tuned control of cell positioning, intercellular interactions, and measurement of biophysical properties. Finally, the review addresses limitations of EF application, such as field heterogeneity and potential side effects, and outlines the directions for future studies, including developing the minimally invasive delivery methods.

The study of the human nervous system remains challenging due to its inherent complexity and difficulty in obtaining original samples. Three-dimensional (3D) bioprinting is a rapidly evolving technology in the field of tissue engineering that has made significant contributions to several disciplines, including neuroscience. In order to more accurately reflect the intricate multicellular milieu of the in vivo environment, an increasing number of studies have commenced experimentation with the coprinting of diverse cell types. This article provides an overview of technical details and the application of 3D bioprinting with multiple cell types in the field of neuroscience, focusing on the challenges of coprinting and the research conducted based on multicellular printing. This review discusses cell interactions in coprinting systems, stem cell applications, the construction of brain-like organoids, the establishment of disease models, and the potential for integrating 3D bioprinting with other 3D culture techniques.

This review synthesizes experimental findings on various biomaterial scaffolds used in eyelid reconstruction. It examines the structural properties, cellular responses, and functional outcomes of scaffolds such as chitosan, poly(propylene glycol fumarate)-2-hydroxyethyl methacrylate, poly(propylene glycol fumarate) - type I collagen (PPF-Col), decellularized matrix-polycaprolactone, branched polyethylene, collagen, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate, and poly(lactic-co-glycolic acid. These scaffolds exhibit diverse mechanical and biological properties, with some demonstrating good biocompatibility, tunable properties, and potential for tissue repair. However, there are limitations, including concerns about long-term functionality and a lack of comprehensive evaluations. This review highlights the need for multifunctional scaffolds that combine lid replacement and ocular surface function restoration, as well as the establishment of standardized research methods. The goal is to guide future innovation in the field and improve the quality of life for patients with eyelid defects.

Colorectal cancer (CRC) recurs at a striking rate, specifically in patients with liver metastasis. Dormant CRC cells disseminated following initial primary tumor resection or treatment often resurface years later to form aggressive, therapy-resistant tumors that result in high patient mortality. Routine imaging-based screenings often fail to detect dormant cancer cell clusters, and there are no overt symptomatic presentations, making dormant CRC a major clinical challenge to diagnose and treat. Tissue engineering approaches are ideally suited to model dormant cancer cells and enable the discovery of therapeutic vulnerabilities or unique mechanistic dependencies of dormant CRC. Emerging evidence suggests that tissue-engineered approaches have been successfully used to model dormant breast and lung cancer. With CRC responsible for the second most cancer-related deaths worldwide and CRC patients commonly experiencing recurrence, it is essential to expand dormancy models to understand this phenomenon in the context of CRC. Most published in vitro models of CRC dormancy simplify the complex tumor microenvironment with two-dimensional culture systems to elucidate dormancy-driving mechanisms. Building on this foundation, future research should apply tissue engineering methods to this growing field to generate competent three-dimensional models and increase mechanistic knowledge. This review summarizes the current state of in vitro CRC dormancy models, highlighting the techniques utilized to give rise to dormant CRC cells: nutrient depletion, anticancer drugs, physical extracellular matrix interactions, and genetic manipulation. The metrics used to validate dormancy within each model are also consolidated to demonstrate the lack of established standards and the ambiguity around comparing studies that have been validated differently. The methods of these studies are organized in this review to increase comprehensibility and identify needs and opportunities for future bioengineered in vitro models to address dormancy-driven mortality in patients with CRC liver metastasis. Impact Statement Dormant cancer drives high patient mortality, especially in metastatic colorectal cancer, owing to the clinical inability to identify dormant cells prior to their overt recurrence. Lacking clinical insights, in vitro modeling for mechanistic and therapeutic discovery is hindered. Here, we review models and methods of inducing colorectal cancer dormancy with the goal of consolidating findings for reference. We also highlight the need for advanced, tissue-engineered models to better mimic the organ-specific 3D microenvironment of metastatic colorectal cancer. New models would enable breakthroughs in understanding mechanisms driving dormancy progression and reversal, thereby providing context for therapeutic advances to improve patient survival.

Peripheral nerve injury (PNI), a challenging neurosurgery issue, often leads to partial or complete loss of neuronal functions and even neuropathic pain. Thus far, the gold standard for treating peripheral nerve deficit remains autografts. While numerous reviews have explored PNI and regeneration, this work distinctively synthesizes recent advancements in tissue engineering-particularly four-dimensional (4D) bioprinting and exosome therapies-with an emphasis on their clinical translation. By consolidating findings spanning molecular mechanisms to therapeutic applications, this review proposes an actionable framework for advancing experimental strategies toward clinically viable solutions. Our work critically evaluates emerging innovations such as dynamically adaptive 4D-printed nerve conduits and exosome-based therapies, underscoring their potential to match conventional autografts in achieving functional restoration. Impact Statement Although several previous reviews have been made on describing with great detail the degenerative and regenerative mechanisms of the peripheral nervous systems, as well as the several existing and exploratory treatment strategies, we focus more on the latest advancements of each of those topics.

Vascular surgery is facing a critical demand for novel vascular grafts that are biocompatible and thromboresistant. This urgency is particularly applicable to bypass operations involving small caliber vessels. In the realm of tissue engineering, the development of fully vascularized organs is promising as a solution to organ shortage for transplantation. To achieve this, it is essential to (re)construct a biocompatible and nonthrombogenic 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 preregistered systematic review of studies published in the last 23 years according to PRISMA-P Guidelines. This comprised 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 (arteriovenous shunt, n = 33), and dynamic in vitro models (n = 38) as the main approaches for thrombogenicity assessment. This comprehensive review reveals a prevalent lack of standardization and provides 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.