Journal of Tissue Engineering最新文献

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.

Tissue engineering and in vitro modeling of the airways and lungs in the respiratory system are of substantial research and clinical importance. In vitro airway and lung models aim to improve treatment options for airway and lung repair and advance respiratory pathophysiological research. The construction of biomimetic native airways and lungs with tissue-specific biological, mechanical, and configurable features remains challenging. Bioprinting, an emerging 3D printing technology, is promising for the development of airway, lung, and disease models, allowing the incorporation of cells and biologically active molecules into printed constructs in a precise and reproducible manner to recreate the airways, lung architecture, and in vitro microenvironment. Herein, we present a review of airway and lung bioprinting for applications in tissue engineering and in vitro modeling. The key pathophysiological characteristics of the airway, lung interstitium, and alveoli are described. The bioinks recently used in 3D bioprinting of the airways and lungs are summarized. Furthermore, we propose a bioink categorization based on the structural characteristics of the lungs and airways. Finally, the challenges and opportunities in the research on biofabrication of airways and lungs are discussed.

Skeletal disorders pose significant challenges to health and quality of life, underscoring the critical need for innovative bone repair methods. Recent studies have spotlighted the promising role of extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) in conjunction with biomimetic peptide (BP) WKYMVm (WK) for bone repair. This research leveraged a self-healing hydrogel as a carrier, effectively loading EVs and WK to enhance treatment efficacy. Through the regulation of vascular formation and osteoblast differentiation, notable advancements were achieved in mending femoral defect bone injuries, offering new possibilities for addressing bone metabolic disorders. The detailed methodology encompassed hydrogel preparation, EVs and WK loading, in vitro cell studies, and rat model experiments. Results unveiled that graphene oxide gelatin hydrogel loaded with wkymvm and extracellular vesicles (GOG@WK-EVs) notably bolstered osteogenic differentiation of bone cells and angiogenesis, while impeding osteoclast differentiation, culminating in potent bone regeneration within femoral defects.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), a life-threatening disease, is typically induced by uncontrolled inflammatory responses and excessive production of reactive oxygen species (ROS). Astaxanthin (Ast) is known for its powerful natural antioxidant properties, showcasing excellent antioxidant, anti-inflammatory, and immunomodulatory effects. However, its poor water solubility and bioavailability significantly limit its efficacy. Taking inspiration from biomimetic biology, this study developed a nasal drug delivery system comprising macrophage membrane (Mϕ)-encapsulated Ast-loaded nanoparticles (Mϕ@Ast-NPs) for the treatment of ALI. Mϕ@Ast-NPs retain the original homing properties of Mϕ, enabling targeted delivery to inflamed lungs and enhancing the anti-inflammatory effects of Astaxanthin (Ast). In vitro and in vivo, Mϕ@Ast-NPs demonstrated excellent biocompatibility and safety, as evidenced by no hemolysis of red blood cells and no significant toxic effects on cells and major organs. To determine the inflammation-targeting of Mϕ@Ast-NPs, both healthy and ALI mice were intranasally administered with Mϕ@Ast-NPs, the results demonstrated that highly targeting to inflamed lungs and endothelia, while with minimal accumulation in healthy lungs and endothelia. Mϕ@Ast-NPs effectively inhibited ROS production, enhanced Nrf2 expression and nucleus translocation, and reduced the levels of pro-inflammatory factors such as IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) in LPS-induced RAW264.7 cells and ALI mice. Our study provided a safe and effective nasal delivery platform for pulmonary diseases, and this biomimetic nano-formulation of Ast could be as functional foods in the future.

There have been remarkable advancements in regenerative medicine for bone regeneration, tackling the worldwide health concern of tissue loss. Tissue engineering uses the body's natural capabilities and applies biomaterials and bioactive molecules to replace damaged or lost tissues and restore their functionality. While synthetic ceramics have overcome some challenges associated with allografts and xenografts, they still need essential growth factors and biomolecules. Combining ceramics and bioactive molecules, such as peptides derived from biological motifs of vital proteins, is the most effective approach to achieve optimal bone regeneration. These bioactive peptides induce various cellular processes and modify scaffold properties by mimicking the function of natural osteogenic, angiogenic and antibacterial biomolecules. The present review aims to consolidate the latest and most pertinent information on the advancements in bioactive peptides, including angiogenic, osteogenic, antimicrobial, and self-assembling peptide nanofibers for bone tissue regeneration, elucidating their biological effects and potential clinical implications.

Fetal bovine serum (FBS) plays a crucial role in the composition of animal cell culture medium. However, conventional serum-based medium face numerous challenges. The use of animal-derived free hydrolysate (ADFH) has garnered significant attention in research and applications as a viable alternative to FBS-containing medium in animal cell culture. This article provides a comprehensive overview of the effects, mechanisms of action, and applications of ADFH in animal cell culture. ADFH serves as an effective substitute for FBS-containing medium, enhancing various cellular processes, including cell proliferation, viability, protein synthesis, production, survival, and stability. Several mechanisms of action for ADFH have been elucidated through scientific investigations, such as nutrient provision, activation of signaling pathways, regulation of protein synthesis and folding, protection against oxidative damage and apoptosis, as well as cell cycle regulation. Researches and applications of ADFH represent a promising approach to overcoming the limitations of FBS-containing medium and advancing the field of animal cell culture. This review provides a theoretical foundation for promoting the development of sustainable and alternative hydrolysates, as well as the continued progress of animal cell culture.

Non-healing bone defects are a pressing public health concern accounting for one main cause for decreased life expectancy and quality. An aging population accompanied with increasing incidence of comorbidities, foreshadows a worsening of this socio-economic problem. Conventional treatments for non-healing bone defects prove ineffective for 5%-10% of fractures. Those challenges not only increase the patient's burden but also complicate medical intervention, underscoring the need for more effective treatment strategies and identification of patients at risk before treatment selection. To address this, our proteomic meta-analysis aims to identify universally affected proteins and functions in the context of bone regeneration that can be utilized as novel bioactive biomaterial functionalizations, drug targets or therapeutics as well as analytical endpoints, or biomarkers in implant design and testing, respectively. We compiled 29 proteomic studies covering cellular models, extracellular vesicles, extracellular matrix, bone tissue, and liquid-biopsies to address different tissue hierarchies and species. An innovative, integrated framework consisting of data harmonization, candidate protein selection, network construction, and functional enrichment as well as drug repurposing and protein scoring metrics was developed. To make this framework widely applicable to other research questions, we have published a detailed tutorial of our meta-analysis process. We identified 51 proteins that are potentially important for bone healing. This includes well-known ECM components such as collagens, fibronectin and periostin, and proteins less explored in bone biology like YWHAE, HSPG2, CCN1, HTRA1, IGFBP7, LGALS1, TGFBI, C3, SERPINA1, and ANXA1 that might be utilized in future bone biomaterial development. Furthermore, we discovered the compounds trifluoperazine, phenethyl isothiocyanate, quercetin, and artenimol, which target key proteins such as S100A4, YWHAZ, MMP2, and TPM4 providing the option to manipulate undesired processes in bone regeneration. This may open new ways for treatment options to face the increasing socio-economic pressure of non-healing bone defects.

The repair and regeneration of tissues and organs using engineered biomaterials has attracted great interest in tissue engineering and regenerative medicine. Recent advances in organoids and engineered organs technologies have enabled scientists to generate 3D tissue that recapitulate the structural and functional characteristics of native organs, opening up new avenues in regenerative medicine. The matrix is one of the most important aspects for improving organoids and engineered organs construction. However, the clinical application of these techniques remained a big challenge because current commercial matrix does not represent the complexity of native microenvironment, thereby limiting the optimal regenerative capacity. Decellularized extracellular matrix (dECM) is expected to maintain key native matrix biomolecules and is believed to hold enormous potential for regenerative medicine applications. Thus, it is worth investigating whether the dECM can be used as matrix for improving organoid and engineered organs construction. In this review, the characteristics of dECM and its preparation method were summarized. In addition, the present review highlights the applications of dECM in the fabrication of organoids and engineered organs.

The demand for skin models as alternatives to animal testing has grown due to ethical concerns and the need for accurate substance evaluation. These alternatives, known as New Approach Methodologies (NAMs), are increasingly used for regulatory decisions. Current skin models from primary human cells often rely on bovine collagen, raising ethical issues. This study explores self-assembled skin models (SASM) as a new method, utilizing hair follicle-derived keratinocytes reprogrammed into induced pluripotent stem cells (iPSC) and differentiated into fibroblasts and keratinocytes. The model relies on the ability of fibroblasts to secrete collagen to produce a xeno-free dermal layer and on the differentiation of keratinocytes to create a functional epidermal layer. These layers exhibited confirmed metabolic activity and the capability to withstand test substances. The successful development of SASM underscores the significance of accurate alternatives in dermatological research, providing an ethical and reliable option for substance evaluation and regulatory testing.