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 βcyclodextrin-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.
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.Clinical limb ischemia (CLI) is the severe manifestation of peripheral arterial disease, which is one of the most common diseases in the population over 70 years old, up to 20%.
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.
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.
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.
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.
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