a-murine-model-of-carotid-aneurysm-formation

A Murine Model of Carotid Aneurysm Formation

Cerebral aneurysms are present in approximately 2%-5% of the population and represent a significant public health concern due to their high rates of ...

McGowan Institute for Regenerative Medicine

Reanimating facial structures following paralysis and muscle loss is a surgical objective that would benefit from improved options for harvesting appropriately sized muscle flaps. The objective of this study is to apply electrohydrodynamic processing to generate a cellularized, elastic, biocomposite scaffold that could develop and mature as muscle in a prepared donor site in vivo, and then be transferred as a thin muscle flap with a vascular and neural pedicle. First, an effective extracellular matrix (ECM) gel type is selected for the biocomposite scaffold from three types of ECM combined with poly(ester urethane)urea microfibers and evaluated in rat abdominal wall defects. Next, two types of precursor cells (muscle-derived and adipose-derived) are compared in constructs placed in rat hind limb defects for muscle regeneration capacity. Finally, with a construct made from dermal ECM and muscle-derived stem cells, protoflaps are implanted in one hindlimb for development and then microsurgically transferred as a free flap to the contralateral limb where stimulated muscle function is confirmed. This construct generation and in vivo incubation procedure may allow the generation of small-scale muscle flaps appropriate for transfer to the face, offering a new strategy for facial reanimation.

Creating and Transferring an Innervated, Vascularized Muscle Flap Made from an Elastic, Cellularized Tissue Construct Developed In Situ.

Cerebral aneurysms are a source of neurological morbidity and mortality, most often as a result of rupture. The most common approach for treating aneurysms involves endovascular embolization using nonbiodegradable medical devices, such as platinum coils. However, the need for retreatment due to the recanalization of coil-treated aneurysms highlights the importance of exploring alternative solutions. In this study, we propose an injectable extracellular matrix-derived embolic formed in situ by Michael addition of gelatin-thiol (Gel-SH) and hyaluronic acid vinyl sulfone (HA-VS) that may be delivered with a therapeutic agent (here, RADA-SP) to fill and remodel aneurysmal tissue without leaving behind permanent foreign bodies. The injectable embolic material demonstrated rapid gelation under physiological conditions, forming a highly porous structure and allowing for cellular infiltration. The injectable embolic exhibited thrombogenic behavior in vitro that was comparable to that of alginate injectables. Furthermore, in vivo studies in a murine carotid aneurysm model demonstrated the successful embolization of a saccular aneurysm and extensive cellular infiltration both with and without RADA-SP at 3 weeks, with some evidence of increased vascular or fibrosis markers with RADA-SP incorporation. The results indicate that the developed embolic has inherent potential for acutely filling cerebrovascular aneurysms and encouraging the cellular infiltration that would be necessary for stable, chronic remodeling.

Article	Year
Creating and Transferring an Innervated, Vascularized Muscle Flap Made from an Elastic, Cellularized Tissue Construct Developed In Situ. Advanced healthcare materials\| PubMed ID: 37499214	2023
Development of an Injectable, ECM-Derivative Embolic for the Treatment of Cerebral Saccular Aneurysms. Biomacromolecules\| PubMed ID: 39001820	2024

Keishi Kohyama

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