Correction: Microenvironment-responsive multifunctional hydrogels with spatiotemporal sequential release of tailored recombinant human collagen type III for the rapid repair of infected chronic diabetic wounds

Correction for ‘Microenvironment-responsive multifunctional hydrogels with spatiotemporal sequential release of tailored recombinant human collagen type III for the rapid repair of infected chronic diabetic wounds’ by Cheng Hu et al., J. Mater. Chem. B, 2021, 9, 9684–9699, DOI: 10.1039/D1TB02170B.

Release of endogenous chondroitin sulfate and heparin as consequence of dysregulated proteolysis in COVID-19

Infection by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), the pathogen responsible for COVID-19, is associated with immune-mediated responses that lead to dysregulated activation of proteolytic enzymes; these contribute to damage to the endothelium, thrombosis, hypercoagulability, and other hematologic complications that include thrombotic thrombocytopenia, a complication of severe COVID-19 as well as a potentially fatal adverse effect of COVID-19 vaccination. Here, it is demonstrated that proteolysis of plasma proteins leads to sequential release of endogenous glycosaminoglycans (GAGs), first chondroitin sulfate (CS), followed by heparin (HP). The extension and degree of what is called "proteolytic storm" determines whether only one endogenous type of GAGs (CS), or both (CS and HP), are released. Sulfated GAGs such as CS and HP exert a protective role against SARS-CoV-2 infection. However, sustained and excessive release of endogenous HP may be responsible for thrombotic thrombocytopenia just as it happens in HP-induced thrombocytopenia (HIT) a well-known side effect of HP administration that results in thromboembolisms in atypical sites, thrombocytopenia, and synthesis of autoantibodies directed against platelet factor 4 (PF4) that contribute to platelet aggregation. It is concluded that release of endogenous HP as consequence of dysregulated proteolysis occurring during COVID-19 or COVID-19 vaccination may play a fundamental role in the pathophysiology of the disease as well as in adverse reactions to vaccination.

A method for the temperature-controlled extraction of DNA from ancient bones v1

We here provide a protocol for the decontamination of ancient bones and teeth that is based on a temperature-controlled, sequential release of DNA. DNA can be extracted from all fractions generated with this method and the fraction with the highest proportion of endogenous DNA identified for further analysis. The protocol proceeds through repeated incubation of the sample powder in phosphate buffer at 37, 60 and 90 °C, followed by the complete lysis of the residual sample powder. As DNA is denatured at high temperature, subsequent DNA extraction and library preparation has to be performed using methods optimized for single-stranded DNA.

Sequential Release of Paclitaxel and Imatinib from Core–Shell Microparticles Prepared by Coaxial Electrospray for Vaginal Therapy of Cervical Cancer

To optimize the anti-tumor efficacy of combination therapy with paclitaxel (PTX) and imatinib (IMN), we used coaxial electrospray to prepare sequential-release core–shell microparticles composed of a PTX-loaded sodium hyaluronate outer layer and an IMN-loaded PLGA core. The morphology, size distribution, drug loading, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, PLGA degradation, cellular growth inhibition, in vivo vaginal retention, anti-tumor efficacy, and local irritation in a murine orthotopic cervicovaginal tumor model after vaginal administration were characterized. The results show that such core–shell microparticles were of spherical appearance, with an average size of 14.65 μm and a significant drug-loading ratio (2.36% for PTX, 19.5% for IMN, w/w), which might benefit cytotoxicity against cervical-cancer-related TC-1 cells. The DSC curves indicate changes in the phase state of PTX and IMN after encapsulation in microparticles. The FTIR spectra show that drug and excipients are compatible with each other. The release profiles show sequential characteristics in that PTX was almost completely released in 1 h and IMN was continuously released for 7 days. These core–shell microparticles showed synergistic inhibition in the growth of TC-1 cells. Such microparticles exhibited prolonged intravaginal residence, a >90% tumor inhibitory rate, and minimal mucosal irritation after intravaginal administration. All results suggest that such microparticles potentially provide a non-invasive local chemotherapeutic delivery system for the treatment of cervical cancer by the sequential release of PTX and IMN.

Sequential Drug Delivery By Injectable Macroporous Hydrogels For Combined Photodynamic-Chemotherapy

With hollow mesoporous silica (hMSN) and injectable macroporous hydrogel (Gel) used as the internal and external drug-loading material respectively, a sequential drug delivery system DOX-CA4P@Gel was constructed, in which combretastatin A4 phosphate (CA4P) and doxorubicin (DOX) were both loaded. The anti-angiogenic drug, CA4P was initially released due to the degradation of Gel, followed by the anti-cell proliferative drug, DOX, released from hMSN in tumor microenvironment. Results showed that CA4P was mainly released at the early stage. At 48 h, CA4P release reached 71.08%, while DOX was only 14.39%. At 144 h, CA4P was 78.20%, while DOX release significantly increased to 61.60%, showing an obvious sequential release behavior. Photodynamic properties of porphyrin endow hydrogel (φΔ(Gel)=0.91) with enhanced tumor therapy effect. In vitro and in vivo experiments showed that dual drugs treated groups have better tumor inhibition than solo drug under near infrared laser irradiation, indicating the effectivity of combined photodynamic-chemotherapy.