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For over 25 years, our group has used regenerative medicine strategies to develop improved biomaterials for use in congenital heart surgery. Among other applications, we developed a tissue-engineered vascular graft (TEVG) by seeding tubular biodegradable polymeric scaffolds with autologous bone marrow-derived mononuclear cells. Results of our first-in-human study demonstrated feasibility as the TEVG transformed into a living vascular graft having an ability to grow, making it the first engineered graft with growth potential. Yet, outcomes of this first Food and Drug Administration-approved clinical trial evaluating safety revealed a prohibitively high incidence of early TEVG stenosis, preventing the widespread use of this promising technology. Mechanistic studies in mouse models provided important insight into the development of stenosis and enabled advanced computational models. Computational simulations suggested both a novel inflammation-driven, mechano-mediated process of in vivo TEVG development and an unexpected natural history, including spontaneous reversal of the stenosis. Based on these in vivo and in silico discoveries, we have been able to rationally design strategies for inhibiting TEVG stenosis that have been validated in preclinical large animal studies and translated to the clinic via a new Food and Drug Administration-approved clinical trial. This progress would not have been possible without the multidisciplinary approach, ranging from small to large animal models and computational simulations. This same process is expected to lead to further advances in scaffold design, and thus next generation TEVGs.

Stroke family caregiver and dyad literature has expanded over the past few years. The purpose of this review was to build upon 2 prior systematic reviews to critique, analyze, and synthesize the evidence pertaining to the impact of family caregiver and dyad interventions on stroke survivor and family caregiver outcomes. CINAHL, PsychINFO, PubMed, and reference lists were searched from December 1, 2016 through March 31, 2021. Using PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), articles were identified that tested outcomes from stroke family caregiver or dyad interventions that targeted the health or well-being of family caregivers. Data from the articles were abstracted into tables for analysis, then compared with recommendations from the 2 prior systematic reviews. A total of 18 articles met inclusion criteria (10 caregiver interventions; 8 dyad interventions) representing sample sizes ranging from 7 to 349 caregivers or dyads. Most were randomized controlled trials (n=13); 2 were cluster randomized trials; and 3 were single-group quasi-experimental designs. Of the 18 studies, 8 had <50 caregivers or dyads and 5 were small feasibility studies that reported data trends rather than testing for significance. Only 6 studies reported significant survivor outcomes. Eleven studies reported significant caregiver outcomes, the most common being burden. A number of survivor and caregiver outcomes were not significant, or only significant for certain subgroups. The limited number of studies, small sample sizes, and conflicting results, made it difficult to draw firm conclusions regarding the impact of these interventions on outcomes. Based on the available evidence from these 18 studies, recommendations from the 2 prior reviews were generally supported. Well-designed and well-powered randomized controlled clinical trials are still needed to confirm efficacy of stroke family caregiver and dyad interventions.