Tissue Engineering. Part B, Reviews最新文献

This review elucidates the complex interplay among oxidative stress (OS), macrophage polarization, and stem cell-driven osteogenesis, emphasizing the regulatory influence of reactive oxygen species (ROS) on bone repair and regeneration. It demonstrates that an imbalance in ROS can impede bone healing by disrupting the equilibrium between pro-inflammatory (M1) and pro-repair (M2) macrophage phenotypes. Furthermore, the review delineates the mechanisms through which ROS can influence mesenchymal stem cell differentiation and osteoclast activity, while also highlighting the body's antioxidant defenses that counteract OS. Innovative strategies are explored, particularly the use of biomaterials and nanomedicine, which aim to modulate ROS levels and macrophage polarization, thereby fostering a conducive microenvironment for bone regeneration. The integration of nanotechnology, biomaterials, and cellular biology emerges as a promising frontier for advancing bone regeneration therapies, with the necessity for clinical validation underscored throughout. Impact Statement This review establishes redox modulation as a paradigm-shifting strategy for bone regeneration. We elucidate how engineered biocomposites precisely recalibrate reactive oxygen species (ROS) to resolve osteo-inflammation, directing macrophage polarization from pro-inflammatory (M1) to pro-regenerative (M2) phenotypes. This immune reprogramming synergistically enhances mesenchymal stem cell osteogenesis and suppresses osteoclastogenesis. By integrating cutting-edge biomaterial design-including enzyme-mimetic nanozymes and organelle-targeted antioxidants-we highlight clinically viable solutions for diabetic bone defects, osteoporosis, and rheumatoid arthritis. Our framework bridges immunology, nanotechnology, and tissue engineering, offering transformative therapeutic avenues for inflammatory osteopathies.

As miniature, three-dimensional emulates of individual human organs generated in vitro, organoids are increasingly recognized as complex, humanized models of development, disease, diagnostics, and drug discovery. Organoids exhibit organ-specific architecture, function, and multicellular composition, can be infinitely derived from pluripotent stem cells, and can be further directed toward organoids of the endocrine or exocrine pancreas. Pancreatic endocrine organoids are rapidly redefining diabetes therapies due to their ability to recapitulate glucose-responsive insulin secretion. Conversely, there is less focus on pancreatic exocrine organoids, which possess untapped potential for investigating disorders such as cancer and cystic fibrosis. This review first summarizes human pancreatic organogenesis to contextualize relevant differentiation pathways, then details protocols that guide human pluripotent stem cells through key developmental stages. Methods to enhance cellular maturation and establish higher-performing end products, as well as the therapeutic value of different pancreatic genres, are assessed. Furthermore, crucial gaps are identified, including limited insight into non-beta-endocrine cells, progenitor lineage bias, and off-target differentiation. By chronicling the advancements of all pancreatic organoid classes, the importance of creating more intricate constructs is underscored, which could lead to their broader application.

Aging is a gradual process leading to the decline of physiological functions across cells, organs, tissues, systems, and the surrounding microenvironment, particularly affecting the musculoskeletal system. Bone aging often presents with osteoporosis and impaired osteogenic niche, thereby increasing fracture risk and decreasing regenerative capacity. Therefore, bone aging and osteoporotic bone defects have become a significant challenge in clinical practice. Tissue-engineered scaffolds are of significant importance in managing osteoporotic bone defects by providing mechanical support, facilitating bone regeneration and repair. They can also serve as a vehicle for drugs or factors for osteoporosis management, thereby enabling localized targeted therapy. The local release of active pharmaceutical agents for the treatment of osteoporosis via biomaterials could serve to reduce the occurrence of systemic side effects, while improving the local aging metabolic microenvironment and immune microenvironment. This review presents a comprehensive discussion of the mechanisms and treatment methods of osteoporosis. The scaffolds used for osteoporotic bone defects are also reviewed. We conducted an in-depth analysis of the impact of diverse preparation techniques and modifications on the osteogenic properties of the scaffolds, and reviewed different materials of drug delivery scaffolds for the repair of osteoporotic bone defects. Finally, we put forward our scientific concept regarding the treatment of bone aging and osteoporotic bone defects. We hope to provide a theoretical basis and research ideas for further in-depth studies on treating osteoporosis and bone aging.

Recent advancements in Parkinson's disease (PD) research have both enriched our pathophysiological understanding and challenged conventional therapeutic dogmas. The emerging application of ectodermal mesenchymal stem cells (EMSCs) derived from the cranial neural crest for neuronal regeneration represents a paradigm-shifting therapeutic modality, diverging fundamentally from traditional dopamine-replacement strategies. However, the fundamental mechanisms responsible for their remarkable neurorestorative potential in PD pathophysiology are still not fully understood. This comprehensive review synthesizes current evidence on the pleiotropic therapeutic capacities of EMSCs, focusing on their ectoderm-derived molecular signatures. Central to this review are developmental insights into nasal mucosa-derived EMSCs, particularly their Nestin⁺ identity, elevated connexin43, niche-specific paracrine activity, and robust dopaminergic differentiation capacity, to guide therapeutic translation for PD. Through systematic interrogation of nasal mucosa-derived EMSC physiology, we aim to establish an evidence-based platform for developing targeted neuroregenerative therapies.

Chitosan is a resorbable cationic polysaccharide known for its biodegradability and electrostatic and self-aggregation properties. Chitosan has been shown to influence Schwann cell proliferation, reduce scarring, support axon growth, and provide superior peripheral nerve regenerative outcomes compared to nerve injuries without chitosan. This article reviews preclinical studies to collectively determine whether the presence of chitosan enhances neuroregenerative outcomes following nerve injury as compared to settings without chitosan. The most consistent outcome measure reported across studies was functional analysis, followed by histomorphometry. Most animal studies showed no significant differences in functional recovery, electrophysiology metrics, and histomorphometry parameters between chitosan-based conduit repairs, reconstruction using autografts, or direct nerve repairs. A subset of studies reported superior outcomes with chitosan conduits for nerve reconstruction, while others indicated inferior results compared to conventional repair. The two human studies focused on digital nerve repair with sensory gaps ≤ 26 mm and demonstrated significantly improved 2-point discrimination at 6 months and equivalent function by 12 months with chitosan conduits compared to standard direct repair. The introduction of chitosan into nerve repair and reconstructions provides a potentially beneficial biological augmentation to the nerve microenvironment that enhances cellular, electrophysiological, and functional outcomes. However, heterogeneous approaches to functional, electrodiagnostic, and histological assessments in addition to varying control groups create a significant deficiency in understanding the true utility of chitosan-based devices within the field of nerve regeneration. Further needs for standardization in the study and comparison of biomaterials for effective clinical translation is needed. Nonetheless, this study highlights papers that are effective in achieving a strong propensity towards the utility of chitosan within biomaterial development for nerve reconstruction.

The development of effective biomaterials for bone defect repair remains challenging due to limitations in mechanical properties, bioactivity, and degradation characteristics. We summarize recent progress in synthetic bone materials, including metals, ceramics, and polymer composites, critically analyzing their clinical strengths and weaknesses. This review presents the fabrication of a new generation of mineralized collagen materials through biomimetic mineralization, demonstrating that their composites exhibit promising clinical application potential. Inspired by the hierarchical architecture of natural bone, a multiscale cascade regulation strategy is further proposed to achieve multidimensional mimicry in composition, structure, mechanical properties, and biological functionality. Special attention is given to multidimensional biomimetic strategies integrating nano-scale molecular self-assembly, electrospinning, and macroscale pressure-driven fusion to construct artificial lamellar bone and artificial cortical bone. In summary, this article provides valuable insights into understanding artificial bone repair materials and their development trends, offering significant guidance for the development of new degradable biomimetic artificial compact bone materials.

The capacity for tissue regeneration declines with age, and cellular senescence is recognized as a critical driver of aging and impaired tissue regeneration potential. Advances in stem cell research have provided new insights into tissue regeneration and stem cell therapy in aging-related diseases. However, stem cell senescence significantly limits their therapeutic efficacy, highlighting the need for effective rejuvenation strategies. Current antisenescence approaches have shown promise, but they still face limitations. This review summarizes and discusses the characteristics and consequences of mesenchymal stem cells (MSCs) senescence and evaluates existing antisenescence strategies. Additionally, recent advancements in biomaterials have demonstrated considerable potential in modulating stem cell fate and enhancing tissue regeneration outcomes. In this context, we explore biomaterial-based approaches for rejuvenating senescent MSCs, offering novel perspectives for advancing tissue regeneration therapies targeting aging-related diseases.

Pelvic organ prolapse (POP) is a common yet complex condition affecting women, characterized by the descent of pelvic organs due to weakened pelvic floor structures. While several treatment strategies exist, their efficacy is often limited, and complications such as surgical failure or recurrence can hinder long-term success. Hydrogels, due to their unique properties such as high-water content, biocompatibility, and flexibility, offer promising potential in the management of POP. This review summarizes various animal models of POP including abdominal wall weakness model, sustained pressure method (vaginal ball stretching), ovariectomy (OVX) model, and gene knockout model. This review further provides a comprehensive overview of the role of hydrogels in POP, highlighting their applications in tissue engineering, drug delivery, and as coatings or injectable materials for prolapsed organs. Furthermore, the challenges in their development were discussed, including material selection, degradability, mechanical properties, and long-term biocompatibility. The strategies to optimize hydrogel performance to better meet clinical needs, with an emphasis on personalization and multifunctionality, were outlined. In conclusion, while hydrogels offer significant promise, further research into their design, application methods, and clinical outcomes is crucial to fully realize their potential in the treatment of POP. Impact Statement This review highlights the transformative potential of hydrogels in treating pelvic organ prolapse, a condition with limited long-term therapeutic success. By systematically analyzing animal models and exploring hydrogel applications in tissue repair and drug delivery, it identifies critical challenges and future directions. The insights offered lay the groundwork for personalized, multifunctional hydrogel systems, guiding future research and accelerating clinical translation.

The poor prognosis constitutes a significant difficulty for spinal cord injury (SCI) individuals. Although mesenchymal stem cells (MSCs) hold promises as advanced therapy medicinal products (ATMPs) for SCI patients, challenges such as Good Manufacturing Practice-compliant manufacturing, cellular senescence, and limited therapeutic efficacy continue to hinder their clinical translation. Recent advances have identified botanical nanovesicles (BNs) as potent bioactive mediators capable of "priming" MSCs to self-rejuvenate, augment paracrine effect, and establish inflammatory tolerance. In this review, we introduce the physicochemical properties of BNs and systematically explore their synergistic relationship with MSCs in regenerative medicine. By integrating BNs with MSC, BNs-empowered MSCs (Be-MSCs) represent next-generation ATMPs. This innovative strategy addresses the limitations of conventional MSC therapies and offers a scalable, nonimmunogenic solution with significant potential for clinical application in SCI.

The reconstruction of critical-sized bone defects remains a challenging clinical problem. At present, the implantation of autogenous and allogeneic grafts is the main clinical treatment strategy but faces some drawbacks, such as inadequate source, donor site-related complications, and immune rejection, driving researchers to develop artificial bone substitutes based on distinct materials and fabrication technologies. Among the bone substitutes, bioceramic-based substitutes exhibit a remarkable biocompatibility, which can also be designed to degrade concomitantly with the formation of new bone. In addition, three-dimensional (3D) printing technologies are frequently used for fabricating personalized 3D bioceramic scaffolds, which can achieve accurate imitation of native bone structures. Especially, bioprinting can produce organoids by integrating cells into scaffolds, which achieves the simultaneous imitation of organ structure and biological function. This review summarizes recent progresses of bioceramic-based materials, including hydroxyapatite, tricalcium phosphate, bioactive glass, calcium silicate, alumina, and zirconia. In addition, the application of 3D printing technologies and bioprinting is also elaborated in this text, offering important reference for future research of 3D-printed bioceramics.