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Abstract Despite the considerable advancements in fabricating polymeric-based scaffolds for tissue engineering, the clinical transformation of these scaffolds remained a big challenge because of the difficulty of simulating native organs/tissues’ microenvironment. As a kind of natural tissue-derived biomaterials, decellularized extracellular matrix (dECM)-based scaffolds have gained attention due to their unique biomimetic properties, providing a specific microenvironment suitable for promoting cell proliferation, migration, attachment and regulating differentiation. The medical applications of dECM-based scaffolds have addressed critical challenges, including poor mechanical strength and insufficient stability. For promoting the reconstruction of damaged tissues or organs, different types of dECM-based composite platforms have been designed to mimic tissue microenvironment, including by integrating with natural polymer or/and syntenic polymer or adding bioactive factors. In this review, we summarized the research progress of dECM-based composite scaffolds in regenerative medicine, highlighting the critical challenges and future perspectives related to the medical application of these composite materials. Graphical Abstract

In order to enhance the bioavailability of poorly water-soluble curcumin, solution-enhanced dispersion by supercritical carbon dioxide (CO2) (SEDS) was employed to prepare curcumin nanoparticles for the first time. A 2(4) full factorial experiment was designed to determine optimal processing parameters and their influence on the size of the curcumin nanoparticles. Particle size was demonstrated to increase with increased temperature or flow rate of the solution, or with decreased precipitation pressure, under processing conditions with different parameters considered. The single effect of the concentration of the solution on particle size was not significant. Curcumin nanoparticles with a spherical shape and the smallest mean particle size of 325 nm were obtained when the following optimal processing conditions were adopted: P = 20 MPa, T = 35°C, flow rate of solution = 0.5 mL·min(-1), concentration of solution = 0.5%. Fourier transform infrared (FTIR) spectroscopy measurement revealed that the chemical composition of curcumin basically remained unchanged. Nevertheless, X-ray powder diffraction (XRPD) and thermal analysis indicated that the crystalline state of the original curcumin decreased after the SEDS process. The solubility and dissolution rate of the curcumin nanoparticles were found to be higher than that of the original curcumin powder (approximately 1.4 μg/mL vs 0.2 μg/mL in 180 minutes). This study revealed that supercritical CO2 technologies had a great potential in fabricating nanoparticles and improving the bioavailability of poorly water-soluble drugs.

In recent times, the co-delivery therapeutics have garnered enormous interest from researchers in the treatment of cancers with multidrug resistance (MDR) due to their efficient delivery of multiple agents, which result in synergistic effects and capable of overcoming all the obstacles of MDR in cancer. However, an efficient delivery platform is required for the conveyance of diverse agents that can successfully devastate MDR in cancer. Initially, short-interfering RNA-loaded chitosan (siRNA-CS) nanoparticles were synthesized using the ionic gelation method. Further, the siRNA-CS nanoparticles and doxorubicin hydrochloride (DOX) were co-loaded in poly-L-lactide porous microparticles (PLLA PMs) (nano-embedded porous microparticles, [NEPMs]) by the supercritical anti-solvent (SAS) process. The NEPM formulation exhibited an excellent aerodynamic performance and sustained release of DOX, which displayed higher anticancer efficacy in drug-resistant cells (human small cell lung cancer, H69AR cell line) than those treated with either free DOX and DOX-PLLA PMs due to the siRNA from CS nanoparticles silenced the MDR gene to DOX therapy. This eco-friendly process provides a convenient way to fabricate such innovative NEPMs co-loaded with a chemotherapeutic agent and a gene, which can devastate MDR in cancer through the co-delivery system.

Compared to various traditional 2D approaches, the scaffold‐based 3D tumor models have emerged as an effective strategy to investigate the complex mechanisms behind cancer progression and responses to drug treatments, by providing biomimetic extracellular matrix and stromal‐like microenvironments including the vascular elements. Herein, the development of a 3D endothelialized hepatic tumor microtissue model based on the fusion of multicellular aggregates of human hepatocellular carcinoma cells and human umbilical vein endothelial cells cocultured in poly(lactic‐co‐glycolic acid)‐based porous microspheres (PLGA PMs) is reported. In contrast to the conventional 2D culture, the cells within the PLGA PMs exhibit significantly higher half‐maximal inhibitory concentration values against anticancer drugs, including doxorubicin and cisplatin. Furthermore, the feasibility of coculturing other cell types, such as fibroblasts (L929) and HepG2 cells, is investigated. Together, the findings emphasize the significance of engineered 3D hepatic tumor microtissue models using PLGA PM‐based multicellular aggregates for drug screening applications. The development of a 3D endothelialized hepatic tumor microtissue model based on the fusion of multicellular aggregates of human hepatocellular carcinoma cells and human umbilical vein endothelial cells cocultured in poly(lactic‐co‐glycolic acid)‐based porous microspheres (PLGA PMs) is reported. The significance of engineered 3D hepatic microtissue models using PLGA PM‐based multicellular aggregates for drug screening applications is demonstrated.

Background Applying traditional fluorescence navigation technologies in hepatocellular carcinoma is severely restricted by high false-positive rates, variable tumor differentiation, and unstable fluorescence performance. Results In this study, a green, economical and safe nanomedicine formulation technology was developed to construct carrier-free indocyanine green nanoparticles (nanoICG) with a small uniform size and better fluorescent properties without any molecular structure changes compared to the ICG molecule. Subsequently, nanoICG dispersed into lipiodol via a super-stable homogeneous intermixed formulation technology (SHIFT&nanoICG) for transhepatic arterial embolization combined with fluorescent laparoscopic hepatectomy to eliminate the existing shortcomings. A 52-year-old liver cancer patient was recruited for the clinical trial of SHIFT&nanoICG. We demonstrate that SHIFT&nanoICG could accurately identify and mark the lesion with excellent stability, embolism, optical imaging performance, and higher tumor-to-normal tissue ratio, especially in the detection of the microsatellite lesions (0.4 × 0.3 cm), which could not be detected by preoperative imaging, to realize a complete resection of hepatocellular carcinoma under fluorescence laparoscopy in a shorter period (within 2 h) and with less intraoperative blood loss (50 mL). Conclusions This simple and effective strategy integrates the diagnosis and treatment of hepatocellular carcinoma, and thus, it has great potential in various clinical applications.

Chronic wound management is an intractable medical and social problem, affecting the health of millions worldwide. Decellularized extracellular matrix (dECM)-based materials possess remarkable biological properties for tissue regeneration, which have been used as commercial products for skin regeneration in clinics. However, the complex external environment and the longer chronic wound-healing process hinder the application of pure dECM materials. dECM-based composite materials are constructed to promote the healing process of different wounds, showing noteworthy functions, such as anti-microbial activity and suitable degradability. Moreover, fabrication technologies for designing wound dressings with various forms have expanded the application of dECM-based composite materials. This review provides a summary of the recent fabrication technologies for building dECM-based composite materials, highlighting advances in dECM-based molded hydrogels, electrospun fibers, and bio-printed scaffolds in managing wounds. The associated challenges and prospects in the clinical application of dECM-based composite materials for wound healing are finally discussed.

We describe a route to the preparation of (metal yolk)/(porous ceria shell) nanostructures through the heterogeneous growth of ceria on porous metal nanoparticles followed by the calcination-induced shrinkage of the nanoparticles. The approach allows for the control of the ceria shell thickness, the metal yolk composition and size, which is difficult to realize through common templating approaches. The yolk/shell nanostructures with monometallic Pt and bimetallic PtAg yolks featuring plasmon-induced broadband light absorption in the visible region are rationally designed and constructed. The superior photocatalytic activities of the obtained nanostructures are demonstrated by the selective oxidation of benzyl alcohol under visible light. The excellent activities are ascribed to the synergistic effects of the metal yolk and the ceria shell on the light absorption, electron-hole separation and efficient mass transfer. Our synthesis of the (metal yolk)/(porous ceria shell) nanostructures points out a way to the creation of sophisticated heteronanostructures for high-performance photocatalysis.

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, chronic inflammation, and subchondral bone remodeling. Conventional intra‐articular therapies provide limited relief and fail to address its multifactorial pathogenesis. Here, we present an injectable hydrogel microsphere platform that integrates antioxidative, anti‐inflammatory, and regenerative functions for localized OA management. Uniform (∼125 µm) chondroitin sulfate methacrylate (ChSMA)‐based microspheres are fabricated via microfluidic photocross‐linking. Manganese dioxide nanoparticles provided catalytic reactive oxygen species (ROS) scavenging, while dexamethasone sodium phosphate enabled sustained release, reducing TNF‐α and IL‐6 levels by ∼30%. Bone marrow mesenchymal stem cells (BMSCs) are co‐delivered to promote cartilage repair. In vitro, the microspheres reduce intracellular ROS, induce M2 macrophage polarization, and suppress inflammatory cytokines by 60–70%, with IL‐10 levels increased by ∼90%. 3D co‐culture supports chondrocyte/BMSC viability and matrix production. In vivo, intra‐articular injection in a rat OA model markedly reduces cartilage erosion, decreases osteophyte volume by 80%, and improves subchondral bone microarchitecture. Histological staining confirms matrix restoration and structural preservation, with Osteoarthritis Research Society International (OARSI) scores reduced by 88%. Collectively, this injectable hydrogel microsphere system offers a minimally invasive and integrated strategy, simultaneously delivering antioxidative, anti‐inflammatory, and regenerative effects for comprehensive OA management. A multifunctional injectable microsphere system is fabricated via UV‐assisted microfluidic cross‐linking, integrating nanozyme‐based ROS scavenging, sustained dexamethasone release, and stem cell delivery. Upon IA injection, the microspheres adapt to joint stress, suppress inflammation, and promote cartilage regeneration, offering a minimally invasive and synergistic strategy for localized treatment of osteoarthritis.

Different divalent metal ions (Ba 2+ , Sr 2+ , Ca 2+ , Zn 2+ ) were selected as crosslinkers. The mechanical properties, cytocompatibility, histocompatibility, cell proliferation and long-term cultivation were investigated. The resulting microcapsules had good sphericity, smooth surface and particle size distribution of 300–400 μm. Sr 2+ microcapsules exhibited a better mechanical strength. The molecular weights cut-off of all membranes were between 24 and 67 kDa. All microcapsules had no cytotoxicity. After intraperitoneal transplantation, the recovered microcapsules still maintained good mechanical strength and morphology with no fibrosis or macrophage aggregation phenomena. The microencapsulated PC12 cells showed no significant variation after recultivation following microcapsule breaking. The cell activity sequence of different microcapsules after 72 h was as follows: bare control cell >Sr 2+  > Ca 2+  > Ba 2+  > Zn 2+ . After 9 weeks’ in vitro culture, the cell survival rate was higher than 80 %. This paper will be of scientific interests for the basic research and clinical application of alginate/chitosan microcapsules embedded with drugs or cells.

The nanoparticles-embedded microcapsules (NEMs) with smooth surface, good sphericity, excellent dispersivity and uniform particle size distribution were prepared by emulsification combined with electrospraying to extend the sustained release performance of the embolic microcapsules loading capecitabine (CAP). The sodium alginate and chitosan with good biocompatibility were used as the materials and CAP as a small-molecule model drug. The drug loading, encapsulation efficiency and drug release of CAP in the NEMs were investigated. The results showed that the drug-loading and encapsulation efficiency both increased with the increment of chitosan and CAP concentration. The maximum values of drug loading and encapsulation efficiency were 1.97 and 18.01 % respectively when initial CAP concentration was 5.0 g/L and chitosan molecular weight 100 kDa. The cumulative release rate of CAP released from the NEMs was lower than 30 % in 0.5 h, which indicated that there was no obvious initial burst release behavior. In the subsequent 240 h, the release results confirmed that the NEMs had better sustained release properties compared to pure microcapsules, and it might be a new anticancer drug delivery system in the future studies.