Tissue Engineering. Part B, Reviews最新文献

Conditions such as congenital abnormalities, cancer, infections, and trauma can severely impact the integrity of the auricular cartilage, resulting in the need for a replacement structure. Current implants, carved from the patient's rib, involve multiple surgeries and carry risks of adverse events such as contamination, rejection, and reabsorption. Tissue engineering aims to develop lifelong auricular bioimplants using different methods, different cell types, growth factors and maintenance media formulations, and scaffolding materials compatible with the host. This review aims to examine the progress in auricular bioengineering, focusing on improvements derived from in vivo models and clinical trials, as well as the author's suggestions to enhance the methods. For this scope review, 30 articles were retrieved through Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, plus 6 manually selected articles. The methods reported in the articles were categorized into four levels according to the development phases: source of cells, cell media supplementation, scaffold, or scaffold-free methods, and experimental in vivo or clinical approaches. Many methods have demonstrated potential for the development of bioimplants; four clinical trials reported a structure like the external ear that could be maintained after overcoming post-transplant inflammation. However, several challenges must be solved, such as obtaining a structure that accurately replicates the shape and size of the patient's healthy contralateral auricle and improvements to avoid immunological rejection and resorption of the bioimplant.

All inorganic nanomaterials such as gold, silica, and cobalt oxide nanoparticles are transforming tissue engineering by providing enantioselective properties with unique characteristics that are mimicking the chirality of biological systems, allowing the precise modulation of cellular behaviors like differentiation and alignment. It is essential for the regeneration of complex tissues such as bone, cartilage, and neural networks, but their clinical application is being obstructed by considerable challenges such as the inability to sustain consistent chirality during synthesis. There are limited means to characterize their molecular structure, the high cost of their production, which constrains their scalability, and the long-term biocompatibility. There are different concerns of these materials in physiological environments, which call for novel solutions such as machine learning-aided synthesis, bioinspired mineralization, and interfacing with cutting-edge technologies such as 3D and 4D bioprinting to design biomimetic scaffolds that facilitate enhanced tissue regeneration. The personalized strategies that are modifying nanomaterial properties to match the distinct requirements of individual patients have the promise of enhancing therapeutic outcomes, and collaborations among materials science, bioengineering, and clinical expertise are needed to standardize protocols, overcome regulatory barriers, and tap the full potential of these nanomaterials. This review is hence a critical appraisal of their revolutionary potential, present limitations, and future promise in enhancing regenerative medicines. [Figure: see text].

Fecal incontinence (FI) severely affects physical and psychological well-being. Artificial anal sphincters (AASs) provide a reconstructive option for patients with severe sphincter damage or congenital dysfunctions, but their clinical application is often limited by complications stemming largely from poor biomechanical compatibility with host tissues. This review examines the physiological mechanisms of defecation as the basis for bionic AAS design and classifies existing devices into two main types: those simulating anorectal angle regulation and those mimicking direct sphincter occlusion. A comparative analysis reveals distinct biomechanical failure modes associated with each approach: angle-modulating devices face challenges like tissue hyperplasia around moving parts, while direct occlusion devices, particularly high-pressure circumferential cuffs, frequently lead to tissue erosion, infection, and mechanical breakdown due to ischemic pressure. Addressing this core issue of biomechanical incompatibility is paramount. Novel mechanical designs, such as constant-force mechanisms, aim to mitigate pressure-induced injury. Furthermore, future optimization directions include enhancing device intelligence through smart sensing and AI algorithms, and exploring biohybrid designs that integrate tissue-engineered components to potentially achieve superior long-term integration. This review underscores that harmonizing mechanical function with the biological environment is critical for improving the safety, efficacy, and longevity of AASs in FI treatment.

Cartilage repair is a common problem in the clinic. Owing to the absence of vascular and lymphatic systems, cartilage exhibits a very limited capacity for self-repair, which complicates related research. The decellularized extracellular matrix (dECM), obtained by removing cellular components, preserves the natural structure and bioactive molecules of native ECM. This offers a biocompatible and bioactive environment for cell growth, making it a suitable and effective biomimetic scaffold material. In recent years, many studies have shown that the dECM has good effects on cartilage regeneration. However, there are no studies on the cartilage regeneration of decellularized matrix from different tissue sources, especially the related mechanisms. This article reviews the preparation methods for dECM and research on decellularized matrix derived from cartilage, fat, synovium, and dermis with respect to cartilage repair and regeneration, and further explores the application value and broad prospects of acellular ECM as a new tissue engineering biomimetic scaffold material. With further progress in dECM research and 3D bioprinting, their combination can better replicate native tissue architecture and function. This approach enables precise control of cells and materials, improves the regenerative niche, and may speed the clinical translation of biomimetic ECM for tissue repair.

Cobalt (Co) and chromium (Cr) are widely used in medical implants due to their strength and biocompatibility. However, implant wear and corrosion can lead to systemic release of these metals, raising concerns about cardiotoxic effects, especially with long-term exposure. This review summarizes current data on the potential cardiotoxicity of implant-derived Co and Cr, focusing on molecular mechanisms, inflammatory responses, and clinical observations. Case reports and clinical studies document considerable variability in serum Co and Cr concentrations postimplantation, influenced by implant type, material composition, and patient-specific factors. While extreme elevations are strongly associated with cardiomyopathy and fibrosis, moderate increases also correlate with subclinical changes such as ventricular dilatation and impaired strain. Nonetheless, many studies fail to find a direct relationship between ion levels and cardiac dysfunction, highlighting the complexity and interindividual variability of toxic responses and underlying pathomechanisms. Existing experimental data suggest that Co and Cr ions interfere with calcium and magnesium handling, impair mitochondrial respiration, and promote the generation of reactive oxygen species. Additionally, both metals can induce inflammatory responses, including cytokine release that results in DNA damage, apoptosis, and impaired cardiomyocyte physiology. Although Co and Cr implants offer substantial clinical benefits, emerging evidence indicates that they may contribute to cardiotoxicity in susceptible individuals. Current findings emphasize the importance of personalized monitoring, including serum ion concentration assessments and advanced imaging techniques. Given the absence of universally accepted toxicity thresholds, further mechanistic and longitudinal clinical studies are essential to define risk stratification strategies, establish safe exposure limits, and improve the cardiovascular safety of patients with metal implants.

The tendon-bone interface (TBI) possesses a highly intricate structure, making complete restoration of its native structure postinjury particularly challenging, which often leads to suboptimal healing outcomes. Metal ions, such as calcium (Ca²⁺), magnesium (Mg²⁺), zinc (Zn²⁺), copper (Cu²⁺), cobalt (Co²⁺), strontium (Sr²⁺), iron (Fe^2+/Fe³⁺), and lithium (Li⁺), have attached significant attention in tissue regeneration research owing to the excellent roles in promoting angiogenesis, osteogenesis, and chondrogenesis. This review systematically elucidates a comprehensive overview of the current understanding of these bioactive ions' mechanisms and their applications in TBI repair. Additionally, the review highlights the importance of incorporating metal ions into biomaterial scaffolds to enhance simultaneous multitissue regeneration while addressing current therapeutic limitations in TBI management. Finally, the review outlines future research directions for optimizing ion-based biomaterial strategies to advance TBI treatment paradigms. Impact Statement The tendon-bone interface (TBI) repair is challenging due to the structural complexity. While a lot of research has focused on restoring TBI functionally and structurally, there is no good strategy to achieve its complete repair. Metal ions play certain roles in promoting the repair of TBI. Therefore, this paper discussed the role of metal ions and materials applied to the TBI in the repair process and related mechanisms, aiming to provide reference for subsequent studies.

The mechanical properties of the extracellular matrix (ECM) play a critical role in regulating cellular behavior and fate. In the design and application of tissue engineering materials, previous studies have primarily focused on the role of material stiffness (elastic modulus) in modulating cellular events. However, biological tissues and the ECM exhibit more complex mechanical behaviors, such as viscoelasticity, highlighting the importance of considering viscoelasticity as a design parameter for biomaterials. Current biomimetic strategies might place less emphasis on the dynamic mechanical microenvironment of viscoelastic ECMs. Emerging evidence suggests that independently tuning the viscoelasticity of matrices can influence cellular biological processes and enhance tissue regeneration outcomes. This review highlights the emerging focus on independently tunable viscoelastic hydrogels and their potential applications in tissue engineering. In this article, we review the design of hydrogels with adjustable viscoelasticity aimed at guiding cellular and tissue behavior, advancing the development of in vitro cell culture models and in vivo regenerative therapies. This review introduces the concept of viscoelasticity, elaborates on the viscoelastic properties of biological tissues, and summarizes commonly used evaluation metrics and characterization techniques for viscoelasticity. Next, it highlights the strategies for constructing hydrogels with tunable viscoelasticity and discusses the regulatory effects of viscoelasticity on cellular behaviors, along with the associated mechanobiological mechanisms and signaling pathways. Finally, the review provides an overview of the current applications of viscoelastic hydrogels in tissue engineering and offers perspectives on future research directions. Impact Statement Viscoelasticity is an essential but often overlooked mechanical property that governs cellular behaviors and tissue remodeling. Recent advances reveal that cells actively sense and respond to viscoelastic cues, influencing adhesion, migration, differentiation, and proliferation. By examining emerging hydrogel designs with independently tunable viscoelasticity, we highlight their potential to enhance cell-instructive biomaterials, improve organoid models, and enable personalized regenerative therapies. This review provides a comprehensive perspective on viscoelasticity-driven cell regulation and offers insights into future directions for designing biomaterials that better mimic native tissue mechanics.

Skin wound healing remains a major clinical challenge. Natural plant extracts have attracted increasing attention due to their high biocompatibility and biosafety, offering effective wound healing while avoiding antibiotic resistance and the development of resistant bacterial strains. Astragaloside IV (AS), a naturally active compound primarily extracted from Astragalus mongholicus Bunge, has demonstrated significant efficacy in promoting skin wound healing. AS is capable of modulating all phases of wound healing, including the inflammatory phase, proliferative phase, and remodeling phase. These effects contribute to reduced inflammation, accelerated tissue regeneration, and controlled scar formation by regulating immune responses and acting on various tissue cells. The potential of AS for clinical application in promoting skin wound healing has been confirmed by numerous in vivo and in vitro studies; however, no comprehensive review has yet been published. This article provides the first systematic overview of the mechanisms by which AS and AS-loaded wound dressings promote wound healing, including the modulation of immune responses in wound healing through antimicrobial, antioxidative stress, and anti-inflammatory activities, and the regulation of endothelial cells, endothelial progenitor cells, fibroblasts, and keratinocytes to promote angiogenesis, collagen deposition, granulation tissue formation, and re-epithelialization. This article also summarizes the common types and advantages of AS-loaded wound dressings. These dressings enhance the bioavailability of AS and enable controlled release, while the incorporation of AS improves their physicochemical properties, thereby markedly enhancing therapeutic efficacy. Finally, the article points out existing research limitations, such as insufficient mechanistic exploration, a limited variety of AS-loaded dressing types, and the absence of clinical trials, and proposes future directions to advance the application. Impact Statement The potential of AS for clinical application in promoting skin wound healing has been confirmed by numerous in vivo and in vitro studies; however, no comprehensive review has yet been published. This article provides the first systematic overview of the mechanisms by which AS and AS-loaded wound dressings promote wound healing. [Figure: see text].

Osseointegration is critical for the long-term success of endosteal implants, as it is influenced by factors such as implant design, material selection, and site of implantation. Considering the structural and vascular properties of trabecular bone, it is reasonable to hypothesize that osseointegration could be enhanced in this region. However, emerging evidence indicates that cortical bone frequently offers a more favorable environment for osseointegration. The objective was to conduct a systematic review of preclinical translational studies comparing osseointegration outcomes around implants placed in cortical and trabecular bone. Preclinical studies comparing bone-to-implant contact (BIC) and bone area fraction occupied (BAFO) between cortical and trabecular regions in animals with solid endosteal implants were retrieved from the PubMed, EMBASE, and Cochrane databases. We included randomized and nonrandomized preclinical translational trials published in English between 2014 and 2024 that reported at least one outcome of interest. Exclusion criteria comprised in vitro or ex vivo experiments, research involving human subjects, studies using powder, liquid, or plasma implants, abstracts, technical descriptions, and narrative or systematic reviews. The systematic review comprised 15 studies, which included a total of 298 animals and 877 implants. The mean follow-up period ranged between 4 and 17 weeks. In 13 studies, the cortical bone region demonstrated higher BIC values, with differences in BIC between cortical and trabecular bone ranging from 5.55% to 49.55% during the first 4 weeks, 1.80% to 51.30% between 4 and 8 weeks, and 9.65% to 35.41% following the 8-week healing period. Regarding BAFO values, data were reported in three studies, all of which indicated elevated values in cortical bone. The mean difference in the first 4 weeks ranged from 15.83% to 29.92%, and from 26.33% to 60.11% after 4 weeks of healing. These findings suggest that cortical regions exhibit enhanced short- and long-term osseointegration outcomes compared to trabecular bone regions. Impact Statement The specific site of implantation significantly influences the degree and rate of osseointegration. Trabecular bone, characterized by its high porosity and larger surface area relative to volume, facilitates the diffusion of nutrients and oxygen from the surrounding marrow and blood vessels. Nevertheless, emerging evidence indicates that cortical bone, due to its greater density and superior mechanical properties, often provides a more stable environment for osseointegration compared to trabecular bone. This systematic review of preclinical studies represents the first comprehensive effort to evaluate and compare osseointegration in cortical versus trabecular bone.

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 in vivo and in vitro studies have been performed to determine the possible mechanisms. Instant in vivo studies focus on adipocytes, stromal vascular fraction cells, fat particles, and growth factors, while in vivo 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.