96,908 results match your criteria biocompatible self-recoverable

Delivery of a spheroids-incorporated human dermal fibroblast sheet increases angiogenesis and M2 polarization for wound healing.

Biomaterials 2021 Jun 7;275:120954. Epub 2021 Jun 7.

School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi, 16419, Republic of Korea. Electronic address:

Low cell engraftment is a major problem in tissue engineering. Although various methods related with cell sheets have been attempted to resolve the issue, low cell viability due to oxygen and nutrient depletion remains an obstacle toward advanced therapeutic applications. Cell therapy using fibroblasts is thought of as a good alternative due to the short doubling times of fibroblasts together with their immunomodulatory properties. Read More

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Asparaginyl Ligase-Catalyzed One-Step Cell Surface Modification of Red Blood Cells.

ACS Chem Biol 2021 Jun 15. Epub 2021 Jun 15.

Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachussets 02115, United States.

Red blood cells (RBCs) can serve as vascular carriers for drugs, proteins, peptides, and nanoparticles. Human RBCs remain in the circulation for ∼120 days, are biocompatible, and are immunologically largely inert. RBCs are cleared by the reticuloendothelial system and can induce immune tolerance to foreign components attached to the RBC surface. Read More

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In Situ Photo-Cross-Linking Hydrogel Accelerates Diabetic Wound Healing through Restored Hypoxia-Inducible Factor 1-Alpha Pathway and Regulated Inflammation.

ACS Appl Mater Interfaces 2021 Jun 15. Epub 2021 Jun 15.

Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055 ,Guangdong, China.

The hypoxia-inducible factor 1-alpha (HIF-1a) pathway plays a key role in regulating angiogenesis during wound healing. However, the diabetic condition hampers the stabilization of HIF-1a and thus inhibits the subsequent angiogenesis, and meanwhile, the function and phenotype transition of macrophage are impaired in the diabetic condition, which leads to prolonged and chronic inflammation. Both angiogenesis inhibition and inflammatory dysfunction make diabetic wound healing a major clinical challenge. Read More

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Comparison of the effects of pre-dilution and post-dilution online hemodiafiltration on the levels of inflammatory markers, lymphocytes, and platelets.

J Artif Organs 2021 Jun 14. Epub 2021 Jun 14.

Hashimoto Clinic, 3-21-5, Hashimoto, Midori-ku, Sagamihara, Kanagawa, Japan.

Online hemodiafiltration (OL-HDF) is a blood purification therapy based on diffusion and ultrafiltration and is classified into two types according to the mode of addition of the substitution fluid: pre-dilution OL-HDF (pre-HDF) and post-dilution OL-HDF (post-HDF); we previously reported that pre-HDF is more biocompatible. However, we used lower blood and substitution flow rates in that study and may not have accurately simulated the treatment conditions used in Europe. In this study, we compared the biocompatibilities of the treatment conditions of pre-HDF, commonly used in Japan, and post-HDF, commonly used in Europe, to determine the most biocompatible treatment conditions. Read More

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Encapsulating bacteria in alginate-based electrospun nanofibers.

Biomater Sci 2021 Jun;9(12):4364-4373

Department of Chemical Engineering, University of Massachusetts, Amherst, Amherst, Massachusetts 01003-9303, USA.

Encapsulation technologies are imperative for the safe delivery of live bacteria into the gut where they regulate bodily functions and human health. In this study, we develop alginate-based nanofibers that could potentially serve as a biocompatible, edible probiotic delivery system. By systematically exploring the ratio of three components, the biopolymer alginate (SA), the carrier polymer poly(ethylene oxide) (PEO), and the FDA approved surfactant polysorbate 80 (PS80), the surface tension and conductivity of the precursor solutions were optimized to electrospin bead-free fibers with an average diameter of 167 ± 23 nm. Read More

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Amphiphilic phospholipid-iodinated polymer conjugates for bioimaging.

Biomater Sci 2021 Jun 15. Epub 2021 Jun 15.

Department of Chemistry, North Carolina Agricultural and Technical State University, Greensboro, North Carolina 27411, USA.

Amphiphilic phospholipid-iodinated polymer conjugates were designed and synthesized as new macromolecular probes for a highly radiopaque and biocompatible imaging technology. Bioconjugation of PEG 2000-phospholipids and iodinated polyesters by click chemistry created amphiphilic moieties with hydrophobic polyesters and hydrophilic PEG units, which allowed their self-assemblies into vesicles or spiked vesicles. More importantly, the conjugates exhibited high radiopacity and biocompatibility in in vitro X-ray and cell viability measurements. Read More

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Ultra-strong bio-glue from genetically engineered polypeptides.

Nat Commun 2021 06 14;12(1):3613. Epub 2021 Jun 14.

Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands.

The development of biomedical glues is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, i.e. strong adhesion and adaption to remodeling processes in healing tissue. Read More

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Hyaluronic acid-based nanogels derived from multicomponent self-assembly for imaging-guided chemo-photodynamic cancer therapy.

Carbohydr Polym 2021 Sep 27;268:118257. Epub 2021 May 27.

Key Laboratory for Organic Electronics and Information Displays, Jiangsu Key Laboratory of Biosensors, Institute of Advanced Materials, Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China. Electronic address:

Multifunctional theranostic nanoplatforms integrated of imaging function, multi-modality therapy, stimuli-responsiveness, and targeted delivery are of highly desirable attributes in achieving precise medicine. However, preparation of multifunctional nanoplatforms often involves laborious, multiple steps and inevitably utilizes low-biocompatible or non-functional components. Herein we report a facile, one-step self-assembly strategy to fabricate hyaluronic acid (HA)-based multifunctional tumor theranostic nanoplatform by employing magnetic resonance imaging (MRI) agent Mn as a reversible crosslink agent for histidine-grafted HA, along with simultaneously loading chemotherapeutic agent doxorubicin hydrochloride (DOX) and photodynamic therapy agent chlorin e6, to realize MRI-guided targeted chemo-photodynamic cancer therapy. Read More

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September 2021

Prospects and challenges of anticancer agents' delivery via chitosan-based drug carriers to combat breast cancer: a review.

Carbohydr Polym 2021 Sep 13;268:118192. Epub 2021 May 13.

The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China. Electronic address:

Breast cancer (BC) is considered as one the most prevalent cancers worldwide. Due to its high resistance to chemotherapy and high probability of metastasis, BC is one of the leading causes of cancer-related deaths. The controlled release of chemotherapy drugs to the precise site of the tumor tissue will increase the therapeutic efficacy and decrease side effects of systemic administration. Read More

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September 2021

Rendering hydrophobic nanoclusters water-soluble and biocompatible.

Chem Sci 2020 Apr 22;11(18):4808-4816. Epub 2020 Apr 22.

Department of Chemistry and Centre for Atomic Engineering of Advanced Materials, Anhui Province Key Laboratory of Chemistry for Inorganic/Organic Hybrid Functionalized Materials, Key Laboratory of Structure and Functional Regulation of Hybrid Materials of Ministry of Education, Anhui University Hefei 230601 P. R. China

Hydrophobic and hydrophilic nanoclusters embody complementary superiorities. The means to amalgamate these superiorities, , the atomic precision of hydrophobic clusters and the water dissolvability of hydrophilic clusters, remains challenging. This work presents a versatile strategy to render hydrophobic nanoclusters water-soluble-the micellization of nanoclusters in the presence of solvent-conjoined Na cations-which overcomes the above major challenge. Read More

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The crucial roles of guest water in a biocompatible coordination network in the catalytic ring-opening polymerization of cyclic esters: a new mechanistic perspective.

Chem Sci 2020 Feb 27;11(12):3345-3354. Epub 2020 Feb 27.

Department of Chemistry, Zhejiang University Hangzhou 310027 P. R. China

The ring-opening polymerization (ROP) of cyclic esters/carbonates is a crucial approach for the synthesis of biocompatible and biodegradable polyesters. Even though numerous efficient ROP catalysts have been well established, their toxicity heavily limits the biomedical applications of polyester products. To solve the toxicity issues relating to ROP catalysts, we report herein a biocompatible coordination network, CZU-1, consisting of Zn(μ-O)(COO) secondary building units (SBUs), biomedicine-relevant organic linkers and guest water, which demonstrates high potential for use in the catalytic ROP synthesis of biomedicine-applicable polyesters. Read More

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February 2020

Alginate-based composites for environmental applications: A critical review.

Crit Rev Environ Sci Technol 2018 Dec;49(4):318-356

Department of Agricultural and Biological Engineering, University of Florida, Gainesville, FL 32611, USA.

Alginate-based composites have been extensively studied for applications in energy and environmental sectors due to their biocompatible, nontoxic, and cost-effective properties. This review is designed to provide an overview of the synthesis and application of alginate-based composites. In addition to an overview of current understanding of alginate biopolymer, gelation process, and cross-linking mechanisms, this work focuses on adsorption mechanisms and performance of different alginate-based composites for the removal of various pollutants including dyes, heavy metals, and antibiotics in water and wastewater. Read More

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December 2018

Characterization of sonochemically prepared human serum albumin nanocapsules using different plant oils as core component for targeted drug delivery.

Ultrason Sonochem 2021 Jun 4;76:105617. Epub 2021 Jun 4.

University of Vienna, Faculty of Life Sciences, Department of Pharmaceutical Technology and Biopharmaceutics, Althanstraße 14, 1090 Vienna, Austria. Electronic address:

The focus of this study is the preparation of proteinaceous human serum albumin (HSA) nanocapsules with biocompatible plant oil cores avoiding toxic cross-linker and noxious non-aqueous liquids. The sonochemical preparation of HSA capsules with different plant oils yields particles with narrow size distribution forming suspensions stable for at least 14 days and enabling long-term storage by freezing. Furthermore, wheat germ agglutinin (WGA) as a targeting molecule was successfully embedded into the proteinaceous particle shell at a molar ratio of 7:1 (HSA/WGA). Read More

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Doxorubicin-loaded natural daptomycin micelles with enhanced targeting and anti-tumor effect in vivo.

Eur J Med Chem 2021 Jun 2;222:113582. Epub 2021 Jun 2.

Ocean NanoTech, LLC, San Diego, CA, 92126, USA. Electronic address:

Development of a simple method to enhance targeting and anti-tumor effect of the chemotherapeutic agents in vivo is a major problem. Amphipathic and natural daptomycin is biocompatible antibacterial polypeptide used in clinical practice. Herein, doxorubicin (DOX) was stabilized by zwitterionic daptomycin (Dap) micelles in aqueous solution to form a zwitterionic nanodrug (Dap-DOX micelles). Read More

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Tuneable Hybrid Hydrogels via Complementary Self-Assembly of a Bioactive Peptide with a Robust Polysaccharide.

ACS Biomater Sci Eng 2021 Jun 14. Epub 2021 Jun 14.

Biofab3D, Aikenhead Centre for Medical Discovery, St Vincent's Hospital Melbourne, Fitzroy, VIC 3065, Australia.

Synthetic materials designed for improved biomimicry of the extracellular matrix must contain fibrous, bioactive, and mechanical cues. Self-assembly of low molecular weight gelator (LMWG) peptides Fmoc-DIKVAV (Fmoc-aspartic acid-isoleucine-lysine-valine-alanine-valine) and Fmoc-FRGDF (Fmoc-phenylalanine-arginine-glycine-aspartic acid-phenylalanine) creates fibrous and bioactive hydrogels. Polysaccharides such as agarose are biocompatible, degradable, and non-toxic. Read More

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Property Regulation of Conjugated Oligoelectrolytes with Polyisocyanide to Achieve Efficient Photodynamic Antibacterial Biomimetic Hydrogels.

ACS Appl Mater Interfaces 2021 Jun 14. Epub 2021 Jun 14.

Institute of Biophysics, Hebei University of Technology, Tianjin 300401, P. R. China.

Fabricating antibacterial hydrogels with antimicrobial drugs and synthetic biocompatible biomimetic hydrogels is a promising strategy for practical medical applications. Here, we report a bicomponent hydrogel composed of a biomimetic polyisocyanopetide (PIC) hydrogel and a photodynamic antibacterial membrane-intercalating conjugated oligoelectrolyte (COE). The aggregation behavior and aggregate size of the COEs in water can be regulated using the PIC hydrogel, which could induce COEs with higher reactive oxygen species (ROS) production efficiency and increased association of COEs toward bacteria, therefore enhancing the antibacterial efficiency. Read More

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Hydrogels Based on Oxidized Cellulose Sulfates and Carboxymethyl Chitosan: Studies on Intrinsic Gel Properties, Stability, and Biocompatibility.

Macromol Biosci 2021 Jun 13:e2100098. Epub 2021 Jun 13.

Department of Biomedical Materials, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 4, 06120, Halle (Saale), Germany.

Cellulose and chitosan are excellent components for the fabrication of bioactive scaffolds, as they are biocompatible and abundantly available. Their derivatives Ocarboxymethyl chitosan (CMChi) and oxidized cellulose sulfate (oxCS) can form in situ gelling, bioactive hydrogels, due to the formation of imine bonds for crosslinking. Here the influence of the degrees of sulfation (DS), oxidation (DO), and the molecular weight of oxCS on intrinsic and rheological properties of such hydrogels and their ability to support the survival and growth of human-adipose-derived stem cells (hADSC) is investigated. Read More

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Fluorescent labeling of biocompatible block copolymers: synthetic strategies and applications in bioimaging.

Mater Adv 2021 Apr 6;2(10):3213-3233. Epub 2021 Apr 6.

Laboratoire de Bioimagerie et Pathologies, UMR 7021, CNRS/Université de Strasbourg 74 route du Rhin 67401 Illkirch-Graffenstaden France

Among biocompatible materials, block copolymers (BCPs) possess several advantages due to the control of their chemistry and the possibility of combining various blocks with defined properties. Consequently, BCPs drew considerable attention as biocompatible materials in the fields of drug delivery, medicine and bioimaging. Fluorescent labeling of BCPs quickly appeared to be a method of choice to image and track these materials in order to better understand the nature of their interactions with biological media. Read More

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Droplet microarrays for cell culture: effect of surface properties and nanoliter culture volume on global transcriptomic landscape.

Mater Today Bio 2021 Jun 30;11:100112. Epub 2021 Apr 30.

Institute of Biological and Chemical Systems-Functional Molecular Systems (IBCS-FMS), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.

The development of novel chemically developed and physically defined surfaces and environments for cell culture and screening is important for various biological applications. The Droplet microarray (DMA) platform based on hydrophilic-superhydrophobic patterning enables high-throughput cellular screening in nanoliter volumes and on various biocompatible surfaces. Here we performed phenotypic and transcriptomic analysis of HeLa-CCL2 cells cultured on DMA, with a goal to analyze cellular response on different surfaces and culture volumes down to 3 nL, compared with conventional cell culture platforms. Read More

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Modulation of the lifespan of by the controlled release of nitric oxide.

Chem Sci 2020 Jul 29;11(33):8785-8792. Epub 2020 Jul 29.

Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering Shanghai China

The frontier of nitric oxide biology has gradually shifted from mechanism elucidation to biomanipulation, cell-proliferation promotion, cell-apoptosis induction, and lifespan modulation. This warrants biocompatible nitric oxide (NO) donating materials, whose NO release is not only controlled by a bioorthogonal trigger, but also self-calibrated allowing real-time monitoring and hence an onset/offset of the NO release. Additionally, the dose of NO release should be facilely adjusted in a large dynamic range; flux and the dose are critical to the biological outcome of NO treatment. Read More

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Introducing charge tag click reaction in living cells for single cell mass spectrometry.

Chem Sci 2020 Jun 23;11(28):7308-7312. Epub 2020 Jun 23.

Hefei National Laboratory for Physical Sciences at the Microscale, School of Chemistry and Materials Science, University of Science and Technology of China Hefei Anhui 230026 P. R. China

For single living cell mass spectrometry measurement, sensitivity is of great significance due to the extremely complicated chemical components of the cytoplasm. Higher sensitivity is always highly desired, especially for chemicals with low concentrations or poor mass spectrometry responses. Here, a quaternary ammonium salt group-based charge tag was designed to enhance the analytical performance for cysteine within single cells using induced nanoelectrospray mass spectrometry. Read More

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Core remodeling leads to long wavelength fluoro-coumarins.

Chem Sci 2020 Jul 3;11(28):7302-7307. Epub 2020 Jul 3.

Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health Frederick Maryland 21702 USA

Low molecular weight, uncharged far-red and NIR dyes would be enabling for a range of imaging applications. Rational redesign of the coumarin scaffold leads to Fluoro-Coumarins (FCs), the lowest molecular weight dyes with emission maxima beyond 700, 800, and 900 nm. FCs display large Stokes shifts and high environmental sensitivity, with a 40-fold increase in emission intensity in hydrophobic solvents. Read More

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Layer-Number-Dependent Effects of Graphene Oxide on the Pluripotency of Mouse Embryonic Stem Cells Through the Regulation of the Interaction Between the Extracellular Matrix and Integrins.

Int J Nanomedicine 2021 4;16:3819-3832. Epub 2021 Jun 4.

Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China.

Introduction: Embryonic stem cells (ESCs) possess great application prospects in biological research and regenerative medicine, so it is important to obtain ESCs with excellent and stable cellular states during in vitro expansion. The feeder layer culture system with the addition of leukemia inhibitory factor (LIF) is currently applied in ESC cultures, but it has a series of disadvantages that could influence the culture efficiency and quality of the ESCs. With the development of nanotechnology, many studies have applied nanomaterials to optimize the stem cell culture system and regulate the fate of stem cells. Read More

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Selenium Nanoparticles for Biomedical Applications: From Development and Characterization to Therapeutics.

Adv Healthc Mater 2021 Jun 13:e2100598. Epub 2021 Jun 13.

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland.

Selenium (Se) is an essential element to human health that can be obtained in nature through several sources. In the human body, it is incorporated into selenocysteine, an amino acid used to synthesize several selenoproteins, which have an active center usually dependent on the presence of Se. Although Se shows several beneficial properties in human health, it has also a narrow therapeutic window, and therefore the excessive intake of inorganic and organic Se-based compounds often leads to toxicity. Read More

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4D Printing of Shape Memory Vascular Stent Based on βCD-g-Polycaprolactone.

Macromol Rapid Commun 2021 Jun 14:e2100176. Epub 2021 Jun 14.

Key Laboratory of Science and Technology on Wear and Protection of Materials, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, 730000, P. R. China.

The 4D-printing technology is applied to fabricate a shape memory peripheral stent with good biocompatibility, which sustains long-term drug release. The star polymer s-PCL is prepared by ring opening polymerization of ε-caprolactone with the -OH of β-cyclodextrin (βCD) as initiator, and then the s-PCL is modified with acrylate endgroup which allows the polymerization under UV light to form the crosslinking network c-PCL. Attributed to the feature of the high crosslinked structure and chemical nature of polycaprolactone (PCL) and βCD, the composite exhibits appropriate tensile strength and sufficient elasticity and bursting pressure, and it is comparable with great saphenous vein in human body. Read More

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Comparison of additive manufactured models of the mandible in accuracy and quality using six different 3D printing systems.

J Craniomaxillofac Surg 2021 Apr 21. Epub 2021 Apr 21.

Department of Oral and Maxillofacial Surgery, University Hospital Heidelberg, University of Heidelberg, Im Neuenheimer Feld 400, D-69120, Heidelberg, Germany. Electronic address:

The aim of this study was to analyze and compare the accuracy and quality of six 3D printing systems available on the market. Data acquisition was performed with 12 scans of human mandibles using an industrial 3D scanner and saved in STL format. These STL files were printed using six different printing systems. Read More

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The importance of pre-formulation studies and of 3D-printed nasal casts in the success of a pharmaceutical product intended for nose-to-brain delivery.

Adv Drug Deliv Rev 2021 Jun 10;175:113826. Epub 2021 Jun 10.

Laboratoire de Pharmacie Galénique et de Biopharmacie, Université libre de Bruxelles (ULB), Brussels, Belgium. Electronic address:

This review aims to cement three hot topics in drug delivery: (a) the pre-formulation of new products intended for nose-to-brain delivery; (b) the development of nasal casts for studying the efficacy of potential new nose-to-brain delivery systems at the early of their development (pre-formulation); (c) the use of 3D printing based on a wide variety of materials (transparent, biocompatible, flexible) providing an unprecedented fabrication tool towards personalized medicine by printing nasal cast on-demand based on CT scans of patients. This review intends to show the links between these three subjects. Indeed, the pathway selected to administrate the drug to the brain not only influence the formulation strategies to implement but also the design of the cast, to get the most convincing measures from it. Read More

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Visible-light excitable Eu-induced hyaluronic acid-chitosan aggregates with heterocyclic ligands for sensitive and fast recognition of hazardous ions.

Int J Biol Macromol 2021 Jun 10;184:188-199. Epub 2021 Jun 10.

Institute of Hybrid Materials, National Center of International Joint Research for Hybrid Materials Technology, National Base of International Sci. & Technology Cooperation on Hybrid Materials, Qingdao University, 308 Ningxia Road, Qingdao 266071, China. Electronic address:

Water-soluble luminescent lanthanide complexes that can be excited with visible light could enable rapid detection of toxic anions and cations in biological systems. Eu-induced hyaluronic acid-chitosan aggregates (EIHCA) can improve the stability, biocompatibility, efficiency, and light absorption of luminescent Eu complexes. Visible-range excitation may avoid phototoxicity associated with overexposure to UV light in biological and ecological applications. Read More

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A multiple environment-sensitive prodrug nanomicelle strategy based on chitosan graftomer for enhanced tumor therapy of gambogic acid.

Carbohydr Polym 2021 Sep 20;267:118229. Epub 2021 May 20.

School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.

A novel multiple environment-sensitive polymeric prodrug of gambogic acid (GA) based on chitosan graftomer was fabricated for cancer treatment. Folic acid-chitosan conjugates was complexed with thermosensitive amine terminated poly-N-isopropylacrylamide (NH-PNIPAM) to develop FA-CSPN. Gambogic acid was conjugated with the graftomer via esterification to achieve high drug-loading capacity and controlled drug release. Read More

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September 2021

Hyaluronic acid dressing of hydrophobic carbon nanodots: A self-assembling strategy of hybrid nanocomposites with theranostic potential.

Carbohydr Polym 2021 Sep 17;267:118213. Epub 2021 May 17.

Lab of Biocompatible Polymers, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, via Archirafi 32, 90123 Palermo, Italy; Institute of Biophysics at Palermo, Italian National Research Council, Via Ugo La Malfa 153, 90146 Palermo, Italy.

We propose a rational design of hyaluronic acid-dressed red-emissive carbon dots (CDs), with a well-structured hydrophobic core capable of locally delivering high amount doxorubicin (Doxo) (> 9% w/w) and heat (hyperthermia) in a light stimuli sensitive fashion. We combined in a unique micelle-like superstructure the peculiar optical properties of CDs (NIR photothermal conversion and red fluorescence) with the ability of hyaluronic acid (HA) shell of stabilizing nanomedicines in aqueous environment and recognizing cancer cells overexpressing CD44 receptors on their membranes, thus giving rise to smart theranostic agents useful in cancer imaging and NIR-triggered chemo-phototherapy of solid tumors. Hydrophobic CDs, named HCDs, were used as functional beads to self-assemble amphiphilic HA derivatives carrying polylactic acid side chains (HA-g-PLA), yielding to light-sensitive and biodegradable core-shell superstructures. Read More

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September 2021