Tissue Engineering. Part B, Reviews最新文献

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.

Three-dimensional printing (3DP) strategies in the field of meniscus and articular disc repair and regeneration have recently garnered significant attention. However, a comprehensive bibliometric assessment to evaluate the scientific progress in this area is lacking. This research aims to explore the development, key areas of focus, and new directions in 3DP techniques for meniscus and articular disc over the last 15 years, considering both structural and temporal perspectives. Academic papers on 3DP approaches for the repair and regeneration of these tissues were retrieved from the Web of Science Core Collection. Bibliometric analysis tools such as R software, CiteSpace, and VOSviewer were utilized to examine the historical patterns, topic evolution, and emerging trends in this domain. For the past 15 years, there has been a steady increase in scholarly attention toward 3DP for the repair of meniscus and articular discs, along with a notable expansion in impactful scientific partnerships. The timeline analysis of references indicates that 3DP methodologies have predominantly shaped the research agenda over the last 10 years, retaining their significance amid annual fluctuations in the focus of citations. Four emerging research subfields were identified through keyword clustering: "mesenchymal stem cells," "fabrication," "scaffolds," and "cartilage." Additionally, we mapped out the top 13 key clusters based on CiteSpace. The time zone view of keyword analysis identified three emerging research niches: "anti-inflammatory and antioxidant," "chondrogenic differentiation," and "silk-based biomaterial-ink." The insights gleaned from these bibliometric studies highlight the current state and trends in 3DP research for meniscus and articular disc, potentially assisting researchers in identifying key focal points and pioneering innovative research directions within this area.

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, I² = 0); amniotic membrane viability (RR = 1.00, 95% CI = 0.93-1.08, I² = 0); ocular congestion resolution (RR = 1.11, 95% CI = 0.97-1.26, I² = 0); fluorescent staining of amniotic membranes on the second day after the operation (RR = 1.31, 95% CI = 0.80-2.14, I² = 11); postoperative recurrence rate (RR = 1.01, 95% CI = 0.50-2.03, I² = 0); and premature lysis of amniotic membrane implants (RR = 0.96, 95% CI = 0.49-1.88, I² = 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.

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.

The increasing number of elderly people across the globe has led to a rise in osteoporosis and bone fractures, significantly impacting the quality of life and posing substantial health and economic burdens. Despite the development of tissue-engineered bone constructs and stem cell-based therapies to address these challenges, their efficacy is compromised by inadequate vascularization and innervation during bone repair. Innervation plays a pivotal role in tissue regeneration, including bone repair, and various techniques have been developed to fabricate innervated bone scaffolds for clinical use. Incorporating neural-related cells and delivering neurotrophic factors are emerging strategies to accelerate bone regeneration through innervation. However, research into neurogenic cell sources remains limited. Meanwhile, neural stem/progenitor cells (NSPCs) are emerging as promising cells for treating neurodegenerative disorders and spinal cord injuries due to their multifunctional capacity in promoting angiogenesis, neurogenesis, and immunomodulation, making them promising candidates for achieving innervation in bone substitutes. In this review, we discuss the regenerative potential of NSPCs in tissue regeneration. We propose their feasibility for bone therapy through their secreted exosomes during traumatic brain injury, contributing to the acceleration of bone healing. Additionally, we discuss the essential neurotrophic factors released from NSPCs and their osteogenic properties. This review emphasizes the necessity for further investigation of the role of NSPCs in bone regeneration.

Coaxial extrusion-based bioprinting (EBB) is an emerging technology that enables the fabrication of biomimetic tissues with precise structural and biological complexities. This three-dimensional bioprinting technique utilizes specialized concentric nozzles to facilitate the simultaneous extrusion of distinct biomaterials, enabling the fabrication of layered constructs that closely resemble native tissues. Unlike traditional extrusion-based methods, coaxial printing allows for independent control over core and shell materials. This enables multimaterial integration, and tailored microenvironments that conventional extrusion methods cannot achieve. Recent technical innovations in coaxial EBB also include improved nozzle designs and bioink formulations, which have contributed to enhanced functional mimicry of native tissues and mechanical integrity of printed constructs. Coaxial EBB has demonstrated potential in spinal cord injury repair, perfusable small-diameter vessel engineering, accurate tumor microenvironment replication for oncology research, and complex organoid systems for personalized medicine. Despite these advancements, persistent challenges in coaxial EBB include maintaining cell viability under shear stress, optimizing bioink rheology, preventing nozzle clogging, and managing regulatory considerations. Future research directions involve the development of predictive computational models and the incorporation of innovative biomaterials for dynamic functionality. Addressing these challenges would allow the full therapeutic and clinical potential of coaxial bioprinting in regenerative medicine to be achieved. This review discusses and summarizes these advancements and limitations in coaxial EBB over the last decade, with an emphasis on applications in regenerative medicine.