Idan Redenski

Bio: Idan Redenski is an academic researcher from Technion – Israel Institute of Technology. The author has contributed to research in topics: Medicine & Tissue engineering. The author has an hindex of 4, co-authored 6 publications receiving 47 citations.

Stimulating Extracellular Vesicles Production from Engineered Tissues by Mechanical Forces.

Abstract: Extracellular vesicles (EVs) have emerged as a promising strategy to promote tissue regeneration. However, overcoming the low EV production yield remains a big challenge in translating EV-based therapies to the clinical practice. Current EV production relies heavily on 2D cell culture, which is not only less physiologically relevant to cells but also requires substantial medium and space. In this study, we engineered tissues seeded with stem cells from dental pulp or adipose tissues, or skeletal muscle cells, and significantly enhanced the EV production yield by applying mechanical stimuli, including flow and stretching, in bioreactors. Further mechanistic investigation revealed that this process was mediated by yes-associated protein (YAP) mechanosensitivity. EVs from mechanically stimulated dental pulp stem cells on 3D scaffolds displayed superior capability in inducing axonal sprouting than the 2D counterparts. Our results demonstrate the promise of this strategy to boost EV production and optimize their functional performance toward clinical translation.

3D Bioprinting of Engineered Tissue Flaps with Hierarchical Vessel Networks (VesselNet) for Direct Host-To-Implant Perfusion.

Abstract: Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel-like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation. Endothelial and support cells spontaneously form microvascular networks in bioprinted tissues using a human collagen bioink. Sacrificial molds are used to create polymeric vessel-like scaffolds and endothelial cells seeded in their lumen form native-like endothelia. Assembling endothelialized scaffolds within vascularizing hydrogels incites the bioprinted vasculature and endothelium to cooperatively create vessels, enabling tissue perfusion through the scaffold lumen. Using a cuffing microsurgery approach, the engineered tissue is directly anastomosed with a rat femoral artery, promoting a rich host vasculature within the implanted tissue. After two weeks in vivo, contrast microcomputer tomography imaging and lectin perfusion of explanted engineered tissues verify the host ingrowth vasculature's functionality. Furthermore, the hierarchical vessel network (VesselNet) supports in vitro functionality of cardiomyocytes. Finally, the proposed approach is expanded to mimic complex structures with native-like millimetric vessels. This work presents a novel strategy aiming to create fully-engineered patient-specific thick tissue flaps.

Spinal Cord Repair: From Cells and Tissue Engineering to Extracellular Vesicles

Abstract: Spinal cord injury (SCI) is a debilitating condition, often leading to severe motor, sensory, or autonomic nervous dysfunction. As the holy grail of regenerative medicine, promoting spinal cord tissue regeneration and functional recovery are the fundamental goals. Yet, effective regeneration of injured spinal cord tissues and promotion of functional recovery remain unmet clinical challenges, largely due to the complex pathophysiology of the condition. The transplantation of various cells, either alone or in combination with three-dimensional matrices, has been intensively investigated in preclinical SCI models and clinical trials, holding translational promise. More recently, a new paradigm shift has emerged from cell therapy towards extracellular vesicles as an exciting “cell-free” therapeutic modality. The current review recapitulates recent advances, challenges, and future perspectives of cell-based spinal cord tissue engineering and regeneration strategies.

Prevascularized Scaffolds Bearing Human Dental Pulp Stem Cells for Treating Complete Spinal Cord Injury

Abstract: The regeneration of injured spinal cord is hampered by the lack of vascular supply and neurotrophic support. Transplanting tissue-engineered constructs with developed vascular networks and neurotrophic factors, and further understanding the pattern of vessel growth in the remodeled spinal cord tissue are greatly desired. To this end, highly vascularized scaffolds embedded with human dental pulp stem cells (DPSCs) are fabricated, which possess paracrine-mediated angiogenic and neuroregenerative potentials. The potent pro-angiogenic effect of the prevascularized scaffolds is first demonstrated in a rat femoral bundle model, showing robust vessel growth and blood perfusion induced within these scaffolds postimplantation, as evidenced by laser speckle contrast imaging and 3D microCT dual imaging modalities. More importantly, in a rat complete spinal cord transection model, the implantation of these scaffolds to the injured spinal cords can also promote revascularization, as well as axon regeneration, myelin deposition, and sensory recovery. Furthermore, 3D microCT imaging and novel morphometric analysis on the remodeled spinal cord tissue demonstrate substantial regenerated vessels, more significantly in the sensory tract regions, which correlates with behavioral recovery following prevascularization treatment. Taken together, prevascularized DPSC-embedded constructs bear angiogenic and neurotrophic potentials, capable of augmenting and modulating SCI repair.

Supporting data for 3D Printed Stem-Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds

Abstract: The ability to model CNS tissues in vitro for in vivo transplantation has the potential to be of critical importance in a variety of medical conditions such as spinal cord injury, traumatic brain injury, stroke, and degenerative neurologic disease. Our approach to generating functional CNS tissue constructs relies on a “multiprong” combination of sophisticated 3D bioprinting and cell culture expertise. Here, as an example for utilizing novel 3D neurobioprinting, we have devised a method to model the cytoarchitecture of spinal cord tissue.

Vascularized organoids on a chip: strategies for engineering organoids with functional vasculature

Abstract: Human organoids, self-organized and differentiated from homogenous pluripotent stem cells (PSC), replicate the key structural and functional characteristics of their in vivo counterparts. Despite the rapid advancement of organoid technology and its diverse applications, major limitations in achieving truly in vivo like functionality have been the lack of matured structural organization and constraints on tissue size, both of which are direct consequences of lacking a functional vasculature. In the absence of perfusable vessels, a core region within organoids quickly becomes necrotic during development due to increased metabolic demands that cannot be met by diffusion alone. Thus, incorporating functional vasculature in organoid models is indispensable for their growth in excess of several hundred microns and maturaturation beyond the embryonic and fetal phase. Here, we review recent advancements in vascularizing organoids and engineering in vitro capillary beds, and further explore strategies to integrate them on a microfluidic based platform, aiming for establishing perfused vasculature throughout organoids in vitro.

3D Printing and Bioprinting Nerve Conduits for Neural Tissue Engineering.

Abstract: Fabrication of nerve conduits for perfectly repairing or replacing damaged peripheral nerve is an urgent demand worldwide, but it is also a formidable clinical challenge. In the last decade, with the rapid development of manufacture technologies, 3D printing and bioprinting have been becoming remarkable stars in the field of neural engineering. In this review, we explore that the biomaterial inks (hydrogels, thermoplastic, and thermoset polyesters and composite) and bioinks have been selected for 3D printing and bioprinting of peripheral nerve conduits. This review covers 3D manufacturing technologies, including extrusion printing, inkjet printing, stereolithography, and bioprinting with inclusion of cells, bioactive molecules, and drugs. Finally, an outlook on the future directions of 3D printing and 4D printing in customizable nerve therapies is presented.