Biology subjects

Domingos, M. A. N.

Publications and source records attributed to Domingos, M. A. N..

2 recordsLinked to original sources

bioRxiv2025

A Modular Bioinstructive Platform for Additive-Free, Topography-Driven Stem Cell Differentiation and Patterning

Recreating 3D bone formation in vitro without biochemical inducers remains a longstanding challenge in preclinical testing. We present a scalable, bioinstructive platform based on polylactic acid microparticles with controlled dimpled surface features that direct mesenchymal stem cell differentiation through endogenous topography-mediated mechanotransduction, establishing a mechanistically validated, additive-free platform. These 3D topographical cues drive cytoskeletal reorganisation and induce osteogenesis via canonical Hedgehog signalling. RNA-Seq revealed early significant upregulation of cytoskeletal components and osteochondral transcription factors, including runt-related transcription factor 2 (RUNX2) and SRY-box transcription factor 9 (SOX9), followed by activation of the insulin growth factor-II pathway and osteogenic commitment. To demonstrate translational potential, two-photon polymerisation lithography was employed to engineer precisely-patterned 3D topographies, inducing graded GLI1 expression without added soluble cues. This establishes a modular, versatile platform for stem cell engineering, offering a topography-driven, non-genetic analogue to mechanogenetics with broad utility for regenerative medicine and human-relevant development of bone models. O_FIG O_LINKSMALLFIG WIDTH=162 HEIGHT=200 SRC="FIGDIR/small/664383v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@1b06d7dorg.highwire.dtl.DTLVardef@1e464e1org.highwire.dtl.DTLVardef@19b1299org.highwire.dtl.DTLVardef@1e21f89_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

bioengineering↗

bioRxiv2023

Effect of a retinoic acid analogue on BMP-driven pluripotent stem cell chondrogenesis

Osteoarthritis is the most common degenerative joint condition, leading to articular cartilage (AC) degradation, chronic pain and immobility. The lack of appropriate therapies that provide tissue restoration combined with the limited lifespan of joint-replacement implants indicate the need for alternative AC regeneration strategies. Differentiation of human pluripotent stem cells (hPSCs) into AC progenitors may provide a long-term regenerative solution but are still limited due to the continued reliance upon growth factors to recapitulate developmental signalling processes. Recently, TTNPB, a small molecule activator of retinoic acid receptors (RARs), has been shown to be sufficient to guide mesodermal specification and early chondrogenesis of hPSCs. Here, we modified our previous differentiation protocol, by supplementing cells with TTNPB and administering BMP2 at specific times to enhance early development. Transcriptomic analyses indicated that activation of RAR signalling significantly upregulated genes related to limb and embryonic skeletal development in the early stages of the protocol and upregulated genes related to AC development in later stages. Chondroprogenitors obtained from RAPID-E could generate cartilaginous pellets that expressed AC-related matrix proteins such as Lubricin, Aggrecan, and Collagen II. This protocol could lay the foundations for cell therapy strategies for osteoarthritis and improve the understanding of AC development in humans.

developmental biology↗