Repair of bone defects remains a major challenge in orthopaedic surgery. Bone tissue engineering is an attractive approach for treating bone loss in various shapes and amounts. The aim of this study was to prepare and evaluate the feasibility of a porous scaffold, which was composed of oligomeric proanthocyanidin crosslinked gelatin mixed with β-tricalcium phosphate (GTP) and was seeded with bone marrow stromal cells (BMSCs) as a bone substitute. GTP scaffolds were made porous using a salt-leaching method. The physicochemical properties of the scaffold were evaluated to determine the optimal salt:composite weight ratio. The results indicated that the GTP scaffold had a favourable macroporous structure and higher porosity when the salt:composite weight ratio was 4:1. Cytotoxic tests demonstrated that extracts from the GTP scaffolds promoted the proliferation of BMSCs. Rat BMSCs were seeded on a GTP scaffold and cultured in a spinner flask. After 2 weeks of culture, scanning electron microscopy observation showed that the cells adhered well to the surfaces of the pores in the scaffold. Moreover, this study explored the biological response of rat calvarial bone to the scaffold to evaluate its potential in bone tissue engineering. Bone defects were filled with BMSC-seeded GTP scaffold and acellular GTP scaffold. After 8 weeks, the scaffold induced new bone formation at a bone defect, as was confirmed by X-ray microradiography and histology. The BMSC-seeded scaffold induced more new bone formation than did an acellular scaffold. These observations suggest that the BMSCs-seeded GTP scaffold can promote the regeneration of defective bone tissue.
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http://dx.doi.org/10.1002/term.1461 | DOI Listing |
PLoS Biol
January 2025
Biochemistry and Molecular Biology and the Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Microtubule nucleation is important for microtubule organization in dendrites and for neuronal injury responses. The core nucleation protein, γTubulin (γTub), is localized to dendrite branch points in Drosophila sensory neurons by Wnt receptors and scaffolding proteins on endosomes. However, whether Wnt ligands are important is unknown.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Materials Science Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Dynamin 1 (Dyn1) GTPase, a principal driver of membrane fission during synaptic endocytosis, self-assembles into short mechanoactive helices cleaving the necks of endocytic vesicles. While structural information about Dyn1 helix is abundant, little is known about the nanoscale dynamics of the helical scaffolding at the moment of fission, complicating mechanistic understanding of Dyn1 action. To address the role of the helix dynamics in fission, we used High-Speed Atomic Force Microscopy (HS-AFM) and fluorescence microscopy to track and compare the spatiotemporal characteristics of the helices formed by wild-type Dyn1 and its K44A mutant impaired in GTP hydrolysis on minimal lipid membrane templates.
View Article and Find Full Text PDFStructure
January 2025
Institute of Physical-Chemistry "Blas Cabrera", CSIC, C/ Serrano 119, 28006 Madrid, Spain. Electronic address:
Nucleoproteins (N) play an essential role in virus assembly and are less prone to mutation than other viral structural proteins, making them attractive targets for drug discovery. Using an NMR fragment-based drug discovery approach, we identified the 1,3-benzothiazol-2-amine (BZT) group as a scaffold to develop potential antivirals for SARS-CoV-2 nucleocapsid (N) protein. A thorough characterization of BZT derivatives using NMR, X-ray crystallography, antiviral activity assays, and intrinsic fluorescence measurements revealed their binding in the C-terminal domain (CTD) domain of the N protein, to residues Arg 259, Trp 330, and Lys 338, coinciding with the nucleotide binding site.
View Article and Find Full Text PDFBioorg Med Chem
October 2023
Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, United States; Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL 32610, United States. Electronic address:
Microtubules, consisting of α/β-tubulin heterodimers, are prime targets for anticancer drug discovery. Gatorbulin-1 (GB1, 1a) is a recently described marine natural product that targets tubulin at a new, seventh pharmacological site at the tubulin intradimer interface. Using our previously developed robust route towards GB1 (1a), we synthesized simplified, first-generation gatorbulins, GB2-7 (1b-1g) of this highly modified cyclodepsipeptide (GB1) that does not contain any proteinogenic amino acid.
View Article and Find Full Text PDFJ Med Chem
November 2024
New Drug Discovery Center (NDDC), Daegu Gyeongbuk Medical Innovation Foundation (K-MEDI hub), 80 Cheombok-ro Dong-gu, Daegu 41061, Korea.
Diabetic retinopathy is a disease that can cause vision loss leading to blindness in people with diabetes. Improved methods to treat and prevent vision loss in diabetic patients are in high demand owing to limited current treatment procedures. Herein, we report a new class of transglutaminase 2 (TGase2) inhibitors for the treatment of diabetic retinopathy based on 7-aminoquinoline-5,8-dione derivatives.
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