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Abstract Abdominal aortic aneurysms (AAA), with approximately 200,000 new diagnoses each year, represent a prevalent clinical concern. Current treatment includes monitoring and surgical procedures once the aneurysm reaches a certain size. However, the lack of effective, timely therapies leads to a high mortality rate due to rupture. With recent advancements and innovations in biomedical science, stem cell therapy has moved closer to widespread clinical use, with the field experiencing rapid growth since its inception in the late 20^thcentury. Given the pathophysiology of AAA, stem cell therapies have high potential impact in the treatment for both early and late-stage disease, targeting underlying mechanisms such as inflammation, vascular degeneration, and extracellular matrix degradation. There are many considerations and innovative potential approaches being explored in this type of treatment, such as strategically leveraging cell properties and their associated secretome and incorporating biomaterials-based strategies. This review article summarizes and critically assesses the efficacy of cell-based therapies in AAA preclinical models, current clinical trials in this area, and other emerging bioengineering approaches for the treatment of AAA. 

Abstract Despite the therapeutic potential of mesenchymal stromal cells (MSC), there is limited understanding of optimal extracellular matrix (ECM) environments to manufacture these cells. We developed tissue chips to study the effects of multi-factorial ECM environments under manufacturable stiffness ranges and multi-component ECM compositions. Manufacturing qualities of cell expansion potential, immunomodulation, and differentiation capacity were examined. The results show stiffness effects, with 900 kPa substrates supporting higher proliferation and osteogenic differentiation, along with anti-inflammatory IL-10 expression, whereas 150 kPa substrates promoted adipogenic differentiation at 150 kPa, suggesting that optimal ECM environments may differ based on manufacturing goals. ECM biochemistries containing fibronectin and laminin further modulated MSC manufacturing qualities across various stiffnesses. Proteomic and transcriptomic analyses revealed unique ECM combinations that induced higher levels of angiogenic and immunomodulatory cytokines, compared to single factor ECMs. These findings demonstrate that optimized ECM environments enhance MSC manufacturing quality. 

Abstract Bioengineering and regenerative medicine strategies are promising for the treatment of vascular diseases. However, current limitations inhibit the ability of these approaches to be translated to clinical practice. Here we summarize some of the big bottlenecks that inhibit vascular regeneration in the disease applications of aortic aneurysms, stroke, and peripheral artery disease. We also describe the bottlenecks preventing three-dimensional bioprinting of vascular networks for tissue engineering applications. Finally, we describe emerging technologies and opportunities to overcome these challenges to advance vascular regeneration. 

Abstract Traumatic muscle injuries associated with volumetric muscle loss (VML) are characterized by muscle loss beyond intrinsic regeneration capacity, leading to permanent functional impairment. Experimental therapies to augment muscle regeneration, such as cell injection, are limited by low cell transplantation capacity, whereas conventional engineered muscle tissue transplants lack geometric customization to conform to the shape of the muscle defect. Here, a facile approach to engineer scaffold‐free high‐density muscle tissues in customizable geometric shapes and sizes with high cell viability and integration potential is developed. Using a facile mold‐based approach to engineer scaffold‐free modular units, transcriptional profiling is performed to uncover the role of pre‐formed cell–cell interactions within scaffold‐free muscle bioconstructs on myogenesis, an the efficacy of muscle bioconstructs in a mouse model of VML is then evaluated. RNA sequencing revealed that pre‐formed cell–cell interactions supported myogenic pathways related to muscle contraction and myofibril assembly, unlike dissociated monodisperse cells. This work further demonstrates the therapeutic efficacy of 3D rectangular solid‐shaped scaffold‐free transplants in improving muscle function and vascular regeneration. Finally, toward clinical translation, the feasibility of this technology to integrate with medical imaging and artificial intelligence‐driven customized bioconstruct design and assembly for intraoperative use is illustrated.