Chlorogenic acid (CGA) is an important bioactive polyphenol with extensive biological properties. This study aimed to fabricate an optimized three-dimensional (3D)-printed capsule scaffold and CGA capsules for targeted delivery of hydrophobic CGA to the colon. The optimized printing parameters identified using the neural network model were a temperature of 170 °C, a printing speed of 20 mm/s, and a nozzle diameter of 0.3 mm. The capsules exhibited slow releasing properties of CGA, and the releasing rates of Eudragit®FS 30D-sealed capsules (due to more cracks and voids) were faster than those of Eudragit®S100-sealed capsules. The Ritger-peppas model was the best fitting model to describe the releasing process of CGA from 8 CGA capsules (R2 ≥ 0.98). All CGA capsules exhibited shear-thinning properties with stable sol-gel viscosity at low shear rates. FTIR spectra confirmed the formation of non-covalent bonds between CGA and the sol. Overall, the obtained 3D-printed capsules provided a promising carrier for the targeted delivery of CGA in the development of personalized dietary supplements.

A sequential delivery system based on MoS2 nanoflower (MoS2 NF) doped chitosan (CS)/oxidized dextran (OD) hydrogels is developed for the treatment of colon cancer. 5-Fluorouracil (5-FU) is combined with polyethylenimine (PEI) decorated MoS2 NF via electrostatic attraction and hydrogen bonding, and the obtained 5-FU/PEI/MoS2 is encapsulated by 1-tetradecanol (TD), a commonly used phase transition material. The resultant TD/5-FU/PEI/MoS2 (TFPM) is then co-encapsulated with methotrexate (MTX) in the CS/OD hydrogels generated via Schiff base reaction and electrostatic attraction. Because the electrostatic attraction between CS and OD is pH-sensitive, MTX and TD/5-FU/PEI/MoS2 can be easily released from the hydrogels at pH 7.4. MoS2 is an outstanding photothermal agent, and the generated hyperthermia under near infrared (NIR) irradiation can lead to the melting of TD and the consequent release of 5-FU encapsulated. More importantly, the generated hyperthermia under NIR irradiation can realize the chemo-photothermal synergistic tumor therapy. Finally, the practicability of the developed sequential delivery system is demonstrated by cytotoxicity test.

Sonochemistry shows remarkable potential in the synthesis or modification of new micro/nanomaterials, particularly the cross-linked emulsions for drug delivery. However, the trend of utilizing sonochemical emulsions for delivery of food-derived bioactive compounds has been just started. The extension of sonochemistry as a tool for engineering bioactive delivery systems will make the approach more universal and greatly increase its applications in the food industry. This review summarizes different types of biopolymeric cross-linked emulsions (CLEs) synthesized via sonochemical approach, including CLEs, surface-modified CLEs, cross-linked high internal phase emulsions, and some novel systems templated on CLEs. Special emphasis is directed toward the cross-linking mechanisms of biopolymers at the oil-water interfaces under acoustic cavitation and the physicochemical principles underlying sonochemical fabrication. We also highlight the advantages and challenges associated with the delivery performance of each system for bioactive compounds. The potential in delivering bioactives using sonochemical emulsions has not been fully reached. There are still a number of issues that need to be overcome, including low cross-linking degree of biopolymers, degradation of bioactives in sonochemical process, and unclear biological fate of encapsulated bioactive compounds. This review may guide future trends in exploring efficient sonochemical strategies and multifunctional delivery systems for food applications.

Despite its wide establishment over the years, iron oxide nanoparticle (IONP) still draws extensive interest in the biomedical fields due to its biocompatibility, biodegradability, magnetivity and surface tunable properties. IONP has been used for the MRI, magnetic targeting, drug delivery and hyperthermia of various diseases. However, their poor stability, low diagnostic sensitivity and low disease-specificity have resulted in unsatisfying diagnostic and therapeutic outputs. The surface functionalization of IONP with biocompatible and colloidally stable components appears to be promising to improve its circulation and colloidal stability. Importantly, through surface functionalization with designated functional components, IONP-based assemblies with multiple stimuli-responsivity could be formed to achieve an accurate and efficient delivery of IONP to disease sites for an improved disease diagnosis and therapy. In this work, we first described the design of biocompatible and stable IONP assemblies. Further, their stimuli-driven manipulation strategies are reviewed. Next, the utilization of IONP assemblies for disease diagnosis, therapy and imaging-guided therapy are discussed. Then, the potential toxicity of IONPs and their clinical usages are described. Finally, the intrinsic challenges and future outlooks of IONP assemblies are commented. This review provides recent insights into IONP assemblies, which could inspire researchers on the future development of multi-responsive and disease-targetable nanoassemblies for biomedical utilization.

Dental pulp necrosis are serious pathologic entities that causes tooth nutrition deficiency and abnormal root development, while regeneration of functional pulp tissue is of paramount importance to regain tooth vitality. However, existing clinical treatments, which focus on replacing the necrotic pulp tissue with inactive filling materials, fail to restore pulp vitality and functions, thus resulting in a devitalized and weakened tooth. Currently, dental pulp regeneration via stem cell-based therapy for pulpless teeth has raised enormous attention to restore the functional pulp. Here, a novel design of injectable simvastatin (SIM) functionalized gelatin methacrylate (GelMA) cryogel microspheres (SMS) loaded with stem cells from human exfoliated deciduous teeth (SHEDs) was established to refine SHEDs biological behaviors and promote in vivo vascularized pulp-like tissue regeneration. In this system, SIM encapsulated poly (lactide-co-glycolide) (PLGA) nanoparticles were incorporated into GelMA cryogel microspheres via cryogelation and O1/W/O2 emulsion method. SMS with sustained release of SIM promoted SHEDs adhesion, proliferation and exhibited cell protection properties during the injection process. Furthermore, SMS enhanced SHEDs odontogenic differentiation and angiogenic potential, and SHEDs loaded SMS (SHEDs/SMS) are beneficial for human umbilical vein endothelial cells (HUVECs) migration and angiogenesis, demonstrating their potential for use in promoting vascularized tissue regeneration. SHEDs/SMS complexes were injected into cleaned human tooth root segments for subcutaneous implantation in nude mice. Our results demonstrated that SHEDs/SMS could induce vessel-rich pulp-like tissue regeneration in vivo and that such an injectable nano-in-micro multistage system for the controlled delivery of bioactive reagents would be suitable for clinical application in endodontic regenerative dentistry.

Over recent decades, amphiphilic block copolymers (ABCs) comprising both hydrophobic and hydrophilic segments within their covalently bound structure have been extensively investigated from basic science to various biomedical applications. Nanoparticles (NPs) self-assembled from ABCs have been a center of interest for controlled delivery of various therapeutic drugs, genes, proteins, and imaging agents for decades and continue to attract attention owing to their unique physical and biological properties. In this Spotlight on Applications, we review and summarize recent optimized preparation techniques in the fabrication of \"drugs\"-loaded NPs from ABCs based on our group progress. These techniques can be categorized into four types including (i) emulsification and solvent evaporation, (ii) double emulsification and solvent evaporation, (iii) nanoprecipitation, and (iv) film dispersion. By selecting proper techniques, bioactive agents with different properties could be incorporated into the NPs either alone or in a combination pattern. We analyze the parameters of various techniques and specifically we highlight the improvements on the improved techniques to simultaneously coload both hydrophilic/hydrophobic drugs and therapeutic nucleic acids in the single NPs. These techniques will allow researchers to select proper methods in designing \"drugs\"-loaded NPs from ABCs.

In situ tissue engineering is a powerful strategy for the treatment of bone defects. It could overcome the limitations of traditional bone tissue engineering, which typically involves extensive cell expansion steps, low cell survival rates upon transplantation, and a risk of immuno-rejection. Here, a porous scaffold polycaprolactone (PCL)/decellularized small intestine submucosa (SIS) was fabricated via cryogenic free-form extrusion, followed by surface modification with aptamer and PlGF-2123-144*-fused BMP2 (pBMP2). The two bioactive molecules were delivered sequentially. The aptamer Apt19s, which exhibited binding affinity to bone marrow-derived mesenchymal stem cells (BMSCs), was quickly released, facilitating the mobilization and recruitment of host BMSCs. BMP2 fused with a PlGF-2123-144 peptide, which showed \"super-affinity\" to the ECM matrix, was released in a slow and sustained manner, inducing BMSC osteogenic differentiation. In vitro results showed that the sequential release of PCL/SIS-pBMP2-Apt19s promoted cell migration, proliferation, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes. The in vivo results demonstrated that the sequential release system of PCL/SIS-pBMP2-Apt19s evidently increased bone formation in rat calvarial critical-sized defects compared to the sequential release system of PCL/SIS-BMP2-Apt19s. Thus, the novel delivery system shows potential as an ideal alternative for achieving cell-free scaffold-based bone regeneration in situ.

Conventional liposomes still face many challenges associated with the poor physical and chemical stability, considerable loss of encapsulated cargo, lack of stimulus responsiveness, and rapid elimination from blood circulation. Integration of versatile functional biopolymers has emerged as an attractive strategy to overcome the limitation of usage of liposomes. This review comprehensively summarizes the most recent studies (2015-2020) and their challenges aiming at the exploration of biopolymer-liposome hybrid systems, including surface-modified liposomes, biopolymer-incorporated liposomes, guest-in-cyclodextrin-in-liposome, liposome-in-hydrogel, liposome-in-film, and liposome-in-nanofiber. The physicochemical principles and key technical information underlying the combined strategies for the fabrication of polymeric liposomes, the advantages and limitations of each of the systems, and the stabilization mechanisms are discussed through various case studies. Special emphasis is directed toward the synergistic efficiencies of biopolymers and phospholipid bilayers on encapsulation, protection, and controlled delivery of bioactives (e.g., vitamins, carotenoids, phenolics, peptides, and other health-related compounds) for the biomedical, pharmaceutical, cosmetic, and functional food applications. The major challenges, opportunities, and possible further developments for future studies are also highlighted.

The recent designs of dynamic nanoassemblies exploiting the tumor-targeting properties have received increasing attention for tumor imaging and therapy due to their tumor-specific delivery and enhanced antitumor efficacy. However, these designs are mainly focused on the macroscopic tumor therapeutic effect, while the nano-bio interactions in the tumor microenvironment (TME) remain poorly understood. This review aims to provide an overview of the development of tumor-responsive nanoassemblies towards the imaging, therapy and TME modulation in the tumor site. The tumor biology leading to TME formation and the potential TME properties for the practicable design of tumor-targeting nanoassemblies has been outlined. Furthermore, the various approaches for TME modification and the realization via dynamic nanoassemblies for enhanced tumor therapy were reviewed. Lastly, the prospects of these methods were briefly discussed. These strategies may inspire the development of new combinational cancer therapeutics.

Supramolecular hydrogels confer control over structural properties in a reversible, dynamic, and biomimetic fashion. The design of supramolecular hydrogels with an improved structural and functional recapitulation of damaged organs is important for clinical applications. For wound healing management, in particular, an effective healing process, through the modulation of epidermal growth factor (EGF) delivery using supramolecular polysaccharide hydrogels, has yet to be developed. In this study, photo-responsive supramolecular polysaccharide hydrogels were formed through host-guest interactions between azobenzene and β-cyclodextrin groups conjugated to hyaluronic acid chains. By exploiting the photoisomerization properties of azobenzene under different wavelengths, a supramolecular hydrogel featuring a dynamic spatial network crosslink density through the application of a light stimulus was obtained. Under ultra violet (UV) light, the loosened hydrogel can rapidly release EGF, thereby enhancing EGF delivery at the wound site. Based on an in vivo assessment of the healing process through a full-thickness skin defect model, the controlled EGF release from a supramolecular hydrogel exhibited superior wound healing efficiency with respect to granulation tissue formation, growth factor levels, and angiogenesis. Therefore, the proposed supramolecular hydrogels are potentially valuable as controlled delivery systems for future clinical wound healing applications.