Journal of Tissue Engineering最新文献

Atopic dermatitis (AD) is a chronic relapsing dermatosis that demands new therapies. This research group previously developed a physically extracted adipose-derived extracellular matrix named adipose collagen fragments (ACF), which was determined containing massive adipose matrix-bound adipokines and medicable on AD through intradermal injection. However, problems concerning the control of drug release and inevitable pain caused by injection hinder the application of ACF in clinics. Microneedle (MN) is a rapid developing technique for precise and painless transdermal drug delivery. Therefore, a dissolving methacrylated gelatin/hyaluronic acid MN patch loaded with ACF was developed in this study. The morphological characteristics, mechanical properties, penetration ability, as well as biocompatibility and degradation efficiency of ACF-MN were evaluated, and its efficacy on ovalbumin-induced AD mice was also investigated. ACF-MN exhibited excellent penetration ability, biocompatibility, degradation efficiency, and satisfying efficacy on murine AD similar with fresh-made ACF. Furthermore, RNA-Seq combining bioinformatics were performed for mechanism exploration. ACF treatment showed a comprehensive efficacy on AD via restoring inflammatory dysregulation, microbiota imbalance, and skin barrier defects. This study offered a novel MN-based ACF-bound adipokines transdermal delivery system that may serve as a promising strategy for relieving AD.

Although various options are available to treat injured organs and peripheral nerves, none is without limitations. Auto- and allografts are the first choice of treatment, but tissue survival or functionality is not guaranteed due to often limited vascular and neural networks. In response, tissue-engineered solutions have been developed, yet clinical translations is rare. In this study, a systematic review was performed on tissue-engineered advancements for peripheral nerves and tissues, to aid future developments in bridging the gap toward the clinic by identifying high-potential solutions and unexplored areas. A systematic search was performed in PubMed, Embase, Web of Science, and Scopus until November 9, 2023. Search terms involved "tissue engineering," "guided," "tissue scaffold," and "tissue graft," together with "innervation" and "reinnervation." Original in vivo or in vitro studies meeting the inclusion criteria (tissue-engineered peripheral nerve/innervation of tissue) and no exclusion criteria (no full text available; written in foreign language; nonoriginal article; tissue-engineering of central nervous system; publication before 2012; insufficient study quality or reproducibility) were assessed. A total of 68 out of 3626 original studies were included. Data extraction was based on disease model, cell origin and host species, biomaterial nature and composition, and external stimuli of biological, chemical or physical origin. Although tissue engineering is still in its infancy, explored innervation strategies of today were highlighted with respect to biomaterials, cell types, and external stimuli. The findings emphasize that natural biomaterials, pre-seeding with autologous cell sources, and solutions for reproductive organs are beneficial for future research. Natural biomaterials possess important cues required for cell-material interaction and closely resemble native tissue in terms of biomechanical, geometrical and chemical composition. Autologous cells induce biomaterial functionalization. As these solutions pose no risk of immunorejection and have demonstrated good outcomes, they are most likely to fulfill the clinical demands.

Advanced in vitro models are crucial for studying human airway biology. Our objective was the development and optimization of 3D in vitro models representing diverse airway regions, including deep lung alveolar region. This initiative was aimed at assessing the influence of selective scaffold materials on distinct airway co-culture models. While PET membranes (30 µm thickness) were unsuitable for alveolar models due to their stiffness and relatively high Young's modulus, a combination of collagenous scaffolds seeded with Calu-3 cells and fibroblasts, showed increased mucus production going from week 1 to week 4 of air lift culture. Meanwhile standard electrospun polymer membrane (50-60 µm thick), which possesses a considerably low modulus of elasticity, offered higher flexibility and supported co-cultures of primary alveolar epithelial (huAEC) and endothelial cells (hEC) in concert with lung biopsy-derived fibroblasts which enhanced maturation of the tissue model. As published, designing human alveolar in vitro models require thin scaffold to mimic the required ultra-thin ECM, in addition to assuring right balanced AT1/AT2 ratio for biomimetic representation. We concluded that co-cultivation of primary/stem cells or cell lines has a higher influence on the function of the airway tissue models than the applied scaffolds.

Rotator cuff tendon injuries often lead to shoulder pain and dysfunction. Traditional treatments such as surgery and physical therapy can provide temporary relief, but it is difficult to achieve complete healing of the tendon, mainly because of the limited repair capacity of the tendon cells. Therefore, it is particularly urgent to explore new treatment methods. In vitro experiments were performed to explore the mechanism of differentiation of umbilical cord mesenchymal stem cells (UCMSCs) to tendon cells and to evaluate their potential in promoting rotator cuff injury repair. Growth factors such as CTGF, GDF-6, and GDF-7 were used to induce the differentiation of UCMSCs, and gene expression changes during the differentiation process were analyzed by single-cell sequencing. Hes1 overexpression and animal models were constructed to study its role in UCMSCs differentiation and rotator cuff injury repair. CTGF was the optimal factor for inducing the differentiation of UCMSCs into tendon cells. With increasing induction time, UCMSCs exhibited obvious tendon cell characteristics, such as changes in cell morphology and increased expression of tendon-specific proteins (MKX, SCX, and TNC). Single-cell sequencing analysis revealed key cellular subpopulations and signaling pathways during differentiation. Furthermore, overexpression of the Hes1 gene significantly promoted the differentiation of UCMSCs to tendon cells and showed its therapeutic effect in rotator cuff injury repair in an animal model. This study confirmed the potential of UCMSCs in tendon injury repair, especially the critical role of Hes1 in promoting UCMSCs differentiation and rotator cuff tendon-bone healing, which provides a theoretical basis and experimental rationale for the development of new cellular therapeutic strategies.

Growing evidence indicates that type 2 diabetes (T2D) is associated with an increased risk of developing Parkinson's disease (PD) through shared disease mechanisms. Studies show that insulin resistance, which is the driving pathophysiological mechanism of T2D plays a major role in neurodegeneration by impairing neuronal functionality, metabolism and survival. To investigate insulin resistance caused pathological changes in the human midbrain, which could predispose a healthy midbrain to PD development, we exposed iPSC-derived human midbrain organoids from healthy individuals to either high insulin concentration, promoting insulin resistance, or to more physiological insulin concentration restoring insulin signalling function. We combined experimental methods with metabolic modelling to identify the most insulin resistance-dependent pathogenic processes. We demonstrate that insulin resistance compromises organoid metabolic efficiency, leading to increased levels of oxidative stress. Additionally, insulin-resistant midbrain organoids showed decreased neuronal activity and reduced amount of dopaminergic neurons, highlighting insulin resistance as a significant target in PD prevention.

Mural cells are essential for maintaining the proper functions of microvasculatures. However, a key challenge of microvascular tissue engineering is identifying a cellular source for mural cells. We showed that in vitro, circulating fibrocytes (CFs) can (1) shear and stabilize the microvasculatures formed by vascular endothelial cells (VECs) in a collagen gel, (2) form gap junctions with VECs and (3) induce basement membrane formation. CFs transplanted into nude mice along with VECs in either collagen gel or Matrigel exhibited activities similar to those mentioned above, that is, sheathing microvasculatures formed by VECs, inducing basement membrane formation and facilitating the connection of the engineered microvasculatures with the host circulation. Interestingly, the behaviour of CFs also differs from that of human brain vascular pericytes (HBVPs) in vitro, which often infiltrate the lumen of capillary-like structures in a mosaic pattern, actively proliferate and exhibit lower endocytosis and migration capacities. We concluded that CFs are a suitable cellular source for mural cells in the construction of tissue-engineered microvasculatures.

Osteonecrosis of the femoral head (ONFH) is a prevalent orthopedic disorder characterized primarily by compromised blood supply. This vascular deficit results in cell apoptosis, trabecular bone loss, and structural collapse of the femoral head at late stage, significantly impairing joint function. While MRI is a highly effective tool for diagnosing ONFH in its early stages, challenges remain due to the limited availability and high cost of MRI, as well as the absence of routine MRI screening in asymptomatic patients. . In addition, current therapeutic strategies predominantly only relieve symptoms while disease-modifying ONFH drugs are still under investigation/development. Considering that blood supply of the femoral head plays a key role in the pathology of ONFH, angiogenic therapies have been put forward as promising treatment options. Emerging bioengineering interventions targeting angiogenesis hold promising potential for ONFH treatment. In this review, we introduce the advances in research into the pathology of ONFH and summarize novel bioengineering interventions targeting angiogenesis. This review sheds light upon new directions for future research into ONFH.

Islet transplantation and more recently stem cell-derived islets were shown to successfully re-establish glycemic control in people with type 1 diabetes under immunosuppression. These results were achieved through intraportal infusion which leads to early graft losses and limits the capacity to contain and retrieve implanted cells in case of adverse events. Extra-hepatic sites and encapsulation devices have been developed to address these challenges and potentially create an immunoprotective or immune-privileged environment. Many strategies have achieved reversal of hyperglycemia in diabetic rodents. So far, the results have been less promising when transitioning to humans and larger animal models due to challenges in oxygenation and insulin delivery. We propose a versatile in vitro perfusion system to culture and experimentally study the function of centimeter-scale tissues and devices for insulin-secreting cell delivery. The system accommodates various tissue geometries, experimental readouts, and oxygenation tensions reflective of potential transplantation sites. We highlight the system's applications by using case studies to explore three prominent bioartificial endocrine pancreas (BAP) configurations: (I) with internal flow, (II) with internal flow and microvascularized, and (III) without internal flow. Oxygen concentration profiles modeled computationally were analogous to viability gradients observed experimentally through live/dead endpoint measurements and in case I, time-lapse fluorescence imaging was used to monitor the viability of GFP-expressing cells in real time. Intervascular BAPs were cultured under flow for up to 3 days and BAPs without internal flow for up to 7 days, showing glucose-responsive insulin secretion quantified through at-line non-disruptive sampling. This system can complement other preclinical platforms to de-risk and optimize BAPs and other artificial tissue designs prior to clinical studies.

The field of three dimensional (3D) bioprinting has witnessed significant advancements, with bioinks playing a crucial role in enabling the fabrication of complex tissue constructs. This review explores the innovative bioinks that are currently shaping the future of 3D bioprinting, focusing on their composition, functionality, and potential for tissue engineering, drug delivery, and regenerative medicine. The development of bioinks, incorporating natural and synthetic materials, offers unprecedented opportunities for personalized medicine. However, the rapid technological progress raises regulatory challenges regarding safety, standardization, and long-term biocompatibility. This paper addresses these challenges, examining the current regulatory frameworks and the need for updated guidelines to ensure patient safety and product efficacy. By highlighting both the technological potential and regulatory hurdles, this review offers a comprehensive overview of the future landscape of bioinks in bioprinting, emphasizing the necessity for cross-disciplinary collaboration between scientists, clinicians, and regulatory bodies to achieve successful clinical applications.

The development of advanced in vitro models for assessing liver toxicity and drug responses is crucial for personalized medicine and preclinical drug development. 3D bioprinting technology provides opportunities to create human liver models that are suitable for conducting high-throughput screening for liver toxicity. In this study, we fabricated a humanized liver model using human-induced hepatocytes (hiHeps) derived from human fibroblasts via a rapid and efficient reprogramming process. These hiHeps were then employed in 3D bioprinted liver models with bioink materials that closely mimic the natural extracellular matrix. The constructed humanized 3D bioprinted livers (h3DPLs) exhibited mature hepatocyte functions, including albumin expression, glycogen storage, and uptake/release of indocyanine green and acetylated low-density lipoprotein. Notably, h3DPLs demonstrated increased sensitivity to hepatotoxic agents such as acetaminophen (APAP), making them a promising platform for studying drug-induced liver injury. Furthermore, our model accurately reflected the impact of rifampin, a cytochrome P450 inducer, on CYP2E1 levels and APAP hepatotoxicity. These results highlight the potential of hiHep-based h3DPLs as a cost-effective and high-performance alternative for personalized liver toxicity screening and preclinical drug testing, paving the way for improved drug development strategies and personalized therapeutic interventions.