Biology subjects

Singh Sandhu, J.

Publications and source records attributed to Singh Sandhu, J..

2 recordsLinked to original sources

bioRxiv2025

Biocompatibility assessment of SilkMA-Gelatin ink tuned for 3D extrusion bioprinting

3D bioprinting applications have led to the development of multifunctional scaffolds that are biocompatible, overcoming shear stress to provide structural integrity. We report the isolation of silk fibroin (SF) using calcium chloride (CaCl2), which was further developed into an ink comprising silkMA and gelatin, demonstrating effective cytocompatibility and biocompatibility when 3D printed using an extrusion-based 3D bioprinter. Rheological characterization of SilkMA-Gelatin showed an improved viscosity and printability of the formulation as compared to an unmodified silk-gelatin composition. SilkMA-gelatin was bioprinted with NIH3T3 cells and demonstrated enhanced viability and proliferation, highlighting its cytocompatibility and ability to support a favourable 3D microenvironment. In vivo biocompatibility of the 3D bioprinted SilkMA-Gelatin was evaluated in Wistar rats, where 3D printed scaffolds maintained structural stability for up to 1 month, with no inflammatory response, progressive cell infiltration, and re-epithelialization. Serum biochemistry analysis, including ALP, ALT, LDH, and Urea (BUN), remained within normal physiological ranges, further confirming systemic safety. Based on the findings, the optimized SilkMA-gelatin ink proves to be highly effective in fabricating cell-laden structures that are stable, exhibit enhanced cytocompatibility and biocompatibility, and offer promising potential for advanced tissue regeneration applications. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/687334v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@1fad3dcorg.highwire.dtl.DTLVardef@6b2d3aorg.highwire.dtl.DTLVardef@6655b8org.highwire.dtl.DTLVardef@85d894_HPS_FORMAT_FIGEXP M_FIG Schematic overview of 3D bioprinting in wound healing and biomedical applications C_FIG

bioengineering↗

bioRxiv2025

BRCA1 is a molecular correlate of cell proliferation in human brain development and in Group 3 and 4 medulloblastoma

The role of the BRCA1-mediated DNA damage repair pathway in regulating human brain development remains unknown, although it has been studied in mouse development. We report evidence for breast cancer type 1 susceptibility protein (BRCA1) being a molecular correlate of proliferation in human neural progenitor cells and in medulloblastoma (MB), a malignant pediatric hindbrain cancer whose cells resemble undifferentiated neural stem cells. In a computational search for molecules potentially keeping Group 3 (G3) and Group 4 (G4) MB tumour cells in a state of stalled differentiation, BRCA1 emerged as a leading candidate gene. We surveyed four independent transcriptomic datasets collectively spanning 142 human developing brain samples, multiple brain regions, and over 1.7 million single cells, and found that BRCA1 transcription is consistently enriched in human neural stem and progenitor cells, relative to differentiating or mature neurons. Across the human lifespan, BRCA1 expression is enriched in the brain during early development, particularly the first trimester of gestation. By analyzing 714 tumours, the largest transcriptomic survey of MB tumours to date, we found that BRCA1 expression is increased in carriers of isochromosome 17q (i17q) aberrations and in G4 MB tumours. Increased BRCA1 expression is associated with worse prognosis in G3 and G4 MB. In the developing cerebellum as well as in the cancer context, BRCA1 expression is correlated with transcription of the cell cycle and DNA damage repair pathways. When considered with previous mouse studies, our work is consistent with a model in which BRCA1 promotes genome surveillance in neural progenitors during human brain development and in G3 and G4 MB tumour growth, thus supporting proliferation.

genomics↗