Strain-Programmed Adhesive Patch for Accelerated Photodynamic Wound Healing.

As an alternative to tissue adhesives, photochemical tissue bonding is investigated for advanced wound healing. However, these techniques suffer from relatively slow wound healing with bleeding and bacterial infections. Here, the versatile attributes of afterglow luminescent particles (ALPs) embedded in dopamine-modified hyaluronic acid (HA-DOPA) patches for accelerated wound healing are presented. ALPs enhance the viscoelastic properties of the patches, and the photoluminescence and afterglow luminescence of ALPs maximize singlet oxygen generation and collagen fibrillogenesis for effective healing in the infected wounds. The patches are optimized to achieve the strong and rapid adhesion in the wound sites. In addition, the swelling and shrinking properties of adhesive patches contribute to a nonlinear behavior in the wound recovery, playing an important role as a strain-programmed patch. The protective patch prevents secondary infection and skin adhesion, and the patch seamlessly detaches during wound healing, enabling efficient residue clearance. In vitro, in vivo, and ex vivo model tests confirm the biocompatibility, antibacterial effect, hemostatic capability, and collagen restructuring for the accelerated wound healing. Taken together, this research collectively demonstrates the feasibility of HA-DOPA/ALP patches as a versatile and promoting solution for advanced accelerated wound healing, particularly in scenarios involving bleeding and bacterial infections.

Effect of chitooligosaccharide on the inhibition of SARS-CoV-2 main protease.

BACKGROUND: The main protease (Mpro) is a crucial target for severe acute respiratory syndrome coronavirus (SARS-CoV-2). Chitooligosaccharide (CS) has broad-spectrum antiviral activity and can effectively inhibit the activity of SARS-CoV. Here, based on the high homology between SARS-CoV-2 and SARS-CoV, this study explores the effect and mechanism of CS with various molecular weights on the activity of SARS-CoV-2 Mpro. METHODS: We used fluorescence resonance energy transfer (FRET), UV-Vis, synchronous fluorescence spectroscopy, circular dichroism (CD) spectroscopy and computational simulation to investigate the molecular interaction and the interaction mechanism between CS and SARS-CoV-2 Mpro. RESULTS: Four kinds of CS with different molecular weights significantly inhibited the activity of Mpro by combining the hydrogen bonding and the salt bridge interaction to form a stable complex. Glu166 appeared to be the key amino acid. Among them, chitosan showed the highest inhibition effect on Mpro enzyme activity and the greatest impact on the spatial structure of protein. Chitosan would be one of the most potential anti-viral compounds. CONCLUSION: This study provides the theoretical basis to develop targeted Mpro inhibitors for the screening and application of anti-novel coronavirus drugs.

Supramolecular host-guest hyaluronic acid hydrogels enhance corneal wound healing through dynamic spatiotemporal effects.

Severe corneal wounds can lead to ulceration and scarring if not promptly and adequately treated. Hyaluronic acid (HA) has been investigated for the treatment of corneal wounds due to its remarkable biocompatibility, transparency and mucoadhesive properties. However, linear HA has low retention time on the cornea while many chemical moieties used to crosslink HA can cause toxicity, which limits their clinical ocular applications. Here, we used supramolecular non-covalent host-guest interactions between HA-cyclodextrin and HA-adamantane to form shear-thinning HA hydrogels and evaluated their impact on corneal wound healing. Supramolecular HA hydrogels facilitated adhesion and spreading of encapsulated human corneal epithelial cells ex vivo and improved corneal wound healing in vivo as an in situ-formed, acellular therapeutic membrane. The HA hydrogels were absorbed within the corneal stroma over time, modulated mesenchymal cornea stromal cell secretome production, reduced cellularity and inflammation of the anterior stroma, and significantly mitigated corneal edema compared to treatment with linear HA and untreated control eyes. Taken together, our results demonstrate supramolecular HA hydrogels as a promising and versatile biomaterial platform for corneal wound healing.

Biomimetic Supramolecular Drug Delivery Hydrogels for Accelerated Skin Tissue Regeneration.

Skin tissue is regenerated by the combinational function of skin cells, extracellular matrix (ECM), and bioactive molecules. As an artificial ECM, supramolecular hydrogels exhibited outstanding capability to mimic the physical properties of ECM. However, the lack of biochemical function in supramolecular hydrogels has limited further tissue engineering applications. Here, we developed self-assembling supramolecular drug delivery hydrogels to mimic the skin tissue regeneration process. The supramolecular hydrogels were prepared to encapsulate fibroblasts by the host-guest interaction of cyclodextrin-modified gelatin (GE-CD) and adamantane-modified hyaluronate (Ad-HA) in conjugation with human growth hormone (hGH) for accelerated skin tissue regeneration. In vitro, GE-CD/Ad-HA-hGH hydrogels showed highly facilitated cell growth by the controlled hGH delivery. After a subcutaneous injection into the back of mice, IVIS imaging of bioengineered fibroblasts to express red fluorescence protein (RFP) revealed prolonged cell survival and proliferation in the supramolecular hydrogels for more than 21 days. We could also observe the improved skin tissue regeneration by the facilitated fibroblast proliferation with angiogenesis. Taken together, we could confirm the feasibility of biomimetic supramolecular drug delivery GE-CD/Ad-HA-hGH hydrogels for various tissue engineering applications.

Emerging Phospholipid Nanobiomaterials for Biomedical Applications to Lab-on-a-Chip, Drug Delivery, and Cellular Engineering.

The design of advanced nanobiomaterials to improve analytical accuracy and therapeutic efficacy has become an important prerequisite for the development of innovative nanomedicines. Recently, phospholipid nanobiomaterials including 2-methacryloyloxyethyl phosphorylcholine (MPC) have attracted great attention with remarkable characteristics such as resistance to nonspecific protein adsorption and cell adhesion for various biomedical applications. Despite many recent reports, there is a lack of comprehensive review on the phospholipid nanobiomaterials from synthesis to diagnostic and therapeutic applications. Here, we review the synthesis and characterization of phospholipid nanobiomaterials focusing on MPC polymers and highlight their attractive potentials for applications in micro/nanofabricated fluidic devices, biosensors, lab-on-a-chip, drug delivery systems (DDSs), COVID-19 potential usages for early diagnosis and even treatment, and artificial extracellular matrix scaffolds for cellular engineering.

Radiative and Non-Radiative Decay Pathways in Carbon Nanodots toward Bioimaging and Photodynamic Therapy.

The origin and classification of energy states, as well as the electronic transitions and energy transfers associated with them, have been recognized as critical factors for understanding the optical properties of carbon nanodots (CNDs). Herein, we report the synthesis of CNDs in an optimized process that allows low-temperature carbonization using ethanolamine as the major precursor and citric acid as an additive. The results obtained herein suggest that the energy states in our CNDs can be classified into four different types based on their chemical origin: carbogenic core states, surface defective states, molecular emissive states, and non-radiative trap states. Each energy state is associated with the occurrence of different types of emissions in the visible to near-infrared (NIR) range and the generation of reactive oxygen species (ROS). The potential pathways of radiative/non-radiative transitions in CNDs have been systematically studied using visible-to-NIR emission spectroscopy and fluorescence decay measurements. Furthermore, the bright photoluminescence and ROS generation of these CNDs render them suitable for in vitro imaging and photodynamic therapy applications. We believe that these new insights into the energy states of CNDs will result in significant improvements in other applications, such as photocatalysis and optoelectronics.

Supramolecular Injectable Hyaluronate Hydrogels for Cartilage Tissue Regeneration.

Mesenchymal stem cells (MSCs) have been widely investigated to repair injured cartilage tissues for the treatment of arthritis. Despite these great efforts, the difficulty in the spatiotemporal control of delivered cells has limited the further clinical development with rapid clearance. Here, we developed injectable hyaluronate (HA) hydrogels to encapsulate MSCs for controlled cartilage tissue regeneration based on the supramolecular chemistry between ß-cyclodextrin-modified HA (HA-CD) and adamantane (Ad)-modified HA (HA-Ad). Supramolecular HA hydrogels exhibited remarkable mechanical characteristics such as shear thinning and self-healing with a high cell viability of encapsulated MSCs. The spatiotemporally controlled delivery of MSCs from the supramolecular HA hydrogels resulted in the statistically significant chondrogenic differentiation and extracellular matrix deposition in vitro and in vivo. We could confirm the notable cartilage tissue regeneration in cartilage defect model rats after treatment with supramolecular HA hydrogels encapsulating MSCs for 28 days. Taken together, supramolecular HA hydrogels would be successfully harnessed as an injectable delivery system of MSCs for cartilage tissue regeneration and other tissue engineering applications.

Supramolecular hydrogels encapsulating bioengineered mesenchymal stem cells for ischemic therapy.

We developed supramolecular hyaluronate (HA) hydrogels to encapsulate genetically engineered mesenchymal stem cells (MSCs) for the treatment of limb ischemia. In vivo angiogenic factors could be produced stably by the bioengineered MSCs (BMSCs) within the supramolecular hydrogels showing effective vascular repair and enhanced blood perfusion.