Biology subjects

Shahin-Shamsabadi, A.

Publications and source records attributed to Shahin-Shamsabadi, A..

3 recordsLinked to original sources

bioRxiv2025

The Tissue Engineering Grail: Seamless Biofabrication of Scaffold-free Hollow Constructs

Scaffold-free tissue engineering enables the construction of biomimetic tissues and organs by preserving cell-cell and cell-matrix interactions while avoiding exogenous scaffolds and biomaterials. Yet current approaches are limited to thin sheets or simple spheroids and often lack cellular maturity and organized extracellular matrix (ECM). Here, Anchored Cell Sheet Engineering, a concept that previously introduced anchors to guide the remodeling of cell sheets into more mature fibers or sheets, is extended to achieve seamless, single-step biofabrication of scaffold-free hollow tubular and spherical constructs for sustained biological and mechanical functions under physiological conditions. Using custom culture devices with curved geometries for two-dimensional (2D) culture, continuous confluent cell-ECM layers were formed that were then delaminated and guided by strategically positioned central cores with different shapes and sizes to undergo tension-mediated remodeling into mechanically stable hollow structures. This approach allows modulation of wall thickness, supports multi-layered architectures, and yields constructs capable of withstanding fluid flow. By expanding scaffold-free biofabrication beyond sheets and fibers to robust hollow geometries, this work establishes a versatile set of physiologically relevant building blocks for scalable bottom-up assembly of complex, multi-tissue organ-like constructs within a bioassembloid framework. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=166 HEIGHT=200 SRC="FIGDIR/small/685834v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@117798eorg.highwire.dtl.DTLVardef@2d6ba1org.highwire.dtl.DTLVardef@1f54547org.highwire.dtl.DTLVardef@197677b_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Muscle-Specific ECM Fibers Made with Anchored Cell Sheet Engineering Support Tissue Regeneration in Rat Models of Volumetric Muscle Loss

Volumetric muscle loss (VML) represents a critical unmet need in regenerative medicine, with no established standard of care. This study introduces a novel therapeutic strategy using tissue-specific skeletal muscle extracellular matrix (ECM) fibers fabricated using scaffold-free Anchored Cell Sheet Engineering technology. These engineered fibers replicate the native ECM composition and microarchitecture of skeletal muscle, incorporating essential structural and basement membrane proteins. In a rat VML model, engineered ECM fibers demonstrated a promising regenerative capacity compared to commercial porcine-derived small intestine submucosa (SIS) ECM. Over an 8-week period, the engineered fibers preserved muscle volume and weight, regulated inflammatory and fibrotic responses, and promoted vascularization. In contrast, SIS was rapidly degraded by week 4 and associated with excessive fibrotic response. Force recovery in the muscles treated with engineered ECM fibers was lower at the 8-week time point (77% compared to 91% in the control group), but histological and immunohistochemical analyses revealed newly formed, dispersed muscle fibers exclusively within the repaired muscle tissue treated with engineered ECM fibers. Importantly, only in cases where engineered ECM fibers were used, muscle weight was preserved, resulting in similar normalized force-to-weight recovery across all groups (87% in the test group vs. 88% in the control group). The histological analyses further demonstrated ongoing tissue remodeling, indicative of sustained regeneration, in contrast to the premature fibrotic healing observed in the other groups. A novel quantitative image analysis workflow using a custom Python script, enabled objective assessment of spatial tissue heterogeneity through histology and immunohistochemistry images, setting a new standard for tissue regeneration analysis. These findings establish engineered tissue-specific ECM fibers as a transformative approach for VML treatment and lay the groundwork for translation to clinical applications.

bioengineering↗

bioRxiv2024

in vivo-like Scaffold-free 3D in vitro Models of Muscular Dystrophies: The Case for Anchored Cell Sheet Engineering in Personalized Medicine

Progress in understanding the underlying mechanisms of muscle dystrophies and finding effective treatments for them has been hindered by the absence of relevant in vitro models for biomedical research. In this study, an entirely scaffold-free cell sheet engineering-based platform is used to make such in vitro models using patient-specific cells. Unlike reductionist bottom-up approaches, this holistic biofabrication method, termed anchored cell sheet engineering, effectively replicated mature cell phenotypes and tissue- and disease-specific ECM deposited by the cells themselves. Robust anchored 3D muscle fibers were developed using primary cells from both healthy individuals and patients with Duchenne dystrophy and Myotonic dystrophy type 1. Through a combination of histology, immunostaining, and proteomics analysis, it was demonstrated that these models formed mature constructs that closely resembled in vivo conditions, outperforming traditional 2D cultures in their translation potential. Models of diseased tissues, analyzed through various analysis, accurately reflected key phenotypic features of the respective diseases. Furthermore, when treated with therapeutically beneficial drugs, the detailed changes in their proteomic profiles were documented. This novel in vitro modeling approach, compared to other 3D techniques that use exogenous scaffolding or bioink, provides a promising platform for advancing the development of muscle dystrophy models, among other conditions.

bioengineering↗