Polydopamine Synergizes with Quercetin Nanosystem to Reshape the Perifollicular Microenvironment for Accelerating Hair Regrowth in Androgenetic Alopecia.

Accumulated reactive oxygen species (ROS) and their resultant vascular dysfunction in androgenic alopecia (AGA) hinder hair follicle survival and cause permanent hair loss. However, safe and effective strategies to rescue hair follicle viability to enhance AGA therapeutic efficiency remain challenging. Herein, we fabricated a quercetin-encapsulated (Que) and polydopamine-integrated (PDA@QLipo) nanosystem that can reshape the perifollicular microenvironment to initial hair follicle regeneration for AGA treatment. Both the ROS scavenging and angiogenesis promotion abilities of PDA@QLipo were demonstrated. In vivo assays revealed that PDA@QLipo administrated with roller-microneedles successfully rejuvenated the "poor" perifollicular microenvironment, thereby promoting cell proliferation, accelerating hair follicle renewal, and facilitating hair follicle recovery. Moreover, PDA@QLipo achieved a higher hair regeneration coverage of 92.5% in the AGA mouse model than minoxidil (87.8%), even when dosed less frequently. The nanosystem creates a regenerative microenvironment by scavenging ROS and augmenting neovascularity for hair regrowth, presenting a promising approach for AGA clinical treatment.

Enhancing organoid culture: harnessing the potential of decellularized extracellular matrix hydrogels for mimicking microenvironments.

Over the past decade, organoids have emerged as a prevalent and promising research tool, mirroring the physiological architecture of the human body. However, as the field advances, the traditional use of animal or tumor-derived extracellular matrix (ECM) as scaffolds has become increasingly inadequate. This shift has led to a focus on developing synthetic scaffolds, particularly hydrogels, that more accurately mimic three-dimensional (3D) tissue structures and dynamics in vitro. The ECM-cell interaction is crucial for organoid growth, necessitating hydrogels that meet organoid-specific requirements through modifiable physical and compositional properties. Advanced composite hydrogels have been engineered to more effectively replicate in vivo conditions, offering a more accurate representation of human organs compared to traditional matrices. This review explores the evolution and current uses of decellularized ECM scaffolds, emphasizing the application of decellularized ECM hydrogels in organoid culture. It also explores the fabrication of composite hydrogels and the prospects for their future use in organoid systems.

Organoid-Based Assessment of Metal-Organic Framework (MOF) Nanomedicines for Ex Vivo Cancer Therapy.

Nanomaterials have been extensively exploited in tumor treatment, leading to numerous innovative strategies for cancer therapy. While nanomedicines present immense potential, their application in cancer therapy is characterized by significant complexity and unpredictability, especially regarding biocompatibility and anticancer efficiency. These considerations underscore the essential need for the development of ex vivo research models, which provide invaluable insights and understanding into the biosafety and efficacy of nanomedicines in oncology. Fortunately, the emergence of organoid technology offers a novel approach to the preclinical evaluation of the anticancer efficacy of nanomedicines in vitro. Hence, in this study, we constructed intestine and hepatocyte organoid models (Intestine-orgs and Hep-orgs) for assessing intestinal and hepatic toxicity at the microtissue level. We utilized three typical metal-organic frameworks (MOFs), ZIF-8, ZIF-67, and MIL-125, as nanomedicines to further detect their interactions with organoids. Subsequently, the MIL-125 with biocompatibility loaded methotrexate (MTX), forming the nanomedicine (MIL-125-PEG-MTX), indicated a high loading efficiency (82%) and a well-release capability in an acid microenvironment. More importantly, the anticancer effect of the nanomedicine was investigated using an in vitro patient-derived organoids (PDOs) model, achieving inhibition rates of 48% and 78% for PDO-1 and PDO-2, respectively, demonstrating that PDOs could predict clinical response and facilitate prospective therapeutic selection. These achievements presented great potential for organoid-based ex vivo models for nano theragnostic evaluation in biosafety and function.

Synthesis of photocrosslinkable hydrogels for engineering three-dimensional vascular-like constructs by surface tension-driven assembly.

Surface tension-driven assembly is a simple routine used in modular tissue engineering to create three-dimensional (3D) biomimetic tissues with desired structural and biological characteristics. A major bottleneck for this technology is the lack of suitable hydrogel materials to meet the requirements of the assembly process and tissue regeneration. Identifying specific requirements and synthesizing novel hydrogels will provide a versatile platform for generating additional biomimetic functional tissues using this approach. In this paper, we present a novel composite hydrogel system based on methacrylated gelatin and γ-polyglutamic acid by UV copolymerization as the building block for fabricating vascular-like tissue via surface tension-driven assembly. The resulting composite hydrogels exhibited the improved mechanical properties and hydrophilicity, which greatly facilitate the assembly process. Subsequent cell encapsulation experiment proved that the hydrogel could provide 3D support for cellular spreading and migration. Furthermore, based on the composite microgel building blocks, cylindrical vascular-like construct with a perfusable microchannel was generated by the needle-assisted sequential assembly. In order to construct a biomimetic vascular tissue, the endothelial cells and smooth muscle cells were encapsulated in the microgels assembly with a spatial arrangement to build a heterogeneous double-layer tubular structure and the cells could readily elongate and migrate in the hollow concentric construct over 3 days. These data suggest that this composite hydrogel is an attractive candidate for surface tension-driven assembly purposes, making the hydrogel potentially applicable in the fabrication of biomimetic vascularized tissues.