E cient manipulation of cell fate is important for regenerative engineering applications. Lineage-speci c differentiation of stem cells is particularly challenging due to their inherent plasticity. Engineered topographies may alter cellular plasticity through contact guidance. However, the ability to rationally design topographies to regulate phenotypic outcomes has been hindered in part by the lack of tools to quantify nanoscale chromatin structure reorganization in live cells. Herein we use micropillars, molecular, and nanostructural quanti cation tools to investigate how nuclear morphology in human mesenchymal stem cells (hMSCs) affects chromatin conformation and osteogenic differentiation. We show that micropillar-induced contact guidance is transduced via the cytoskeleton and impacts nuclear architecture, lamin A/C multimerization, histone modi cations, and the 3-D conformation of chromatin within packing domains, a key regulator of transcriptional responsiveness. Micropillars repressed expression of genes associated with developmental processes and enhanced lineage-speci c responsiveness, thereby decreasing cell plasticity and off-target differentiation, and facilitating osteogenic differentiation of hMSCs. Altogether, these ndings reveal that chromatin reprogramming through contact guidance-induced nuclear deformation can be an e cient way to manipulate cell fate.
Impaired wound healing is a common complication for diabetic patients and effective diabetic wound management remains a clinical challenge. Furthermore, a significant problem that contributes to patient morbidity is the suboptimal quality of healed skin, which often leads to reoccurring chronic skin wounds. Herein, a novel compound and biomaterial building block, panthenol citrate (PC), is developed. It has interesting fluorescence and absorbance properties, and it is shown that PC can be used in soluble form as a wash solution and as a hydrogel dressing to address impaired wound healing in diabetes. PC exhibits antioxidant, antibacterial, anti‐inflammatory, and pro‐angiogenic properties, and promotes keratinocyte and dermal fibroblast migration and proliferation. When applied in a splinted excisional wound diabetic rodent model, PC improves re‐epithelialization, granulation tissue formation, and neovascularization. It also reduces inflammation and oxidative stress in the wound environment. Most importantly, it improves the regenerated tissue quality with enhanced mechanical strength and electrical properties. Therefore, PC could potentially improve wound care management for diabetic patients and play a beneficial role in other tissue regeneration applications.
Myocardial infarction (MI) is one of the leading causes of death and disability. Recently developed cardiac patches provide mechanical support and additional conductive paths to promote electrical signal propagation in the MI area to synchronize cardiac excitation and contraction. Cardiac patches based on conductive polymers offer attractive features; however, the modest levels of elasticity and high impedance interfaces limit their mechanical and electrical performance. These structures also operate as permanent implants, even in cases where their utility is limited to the healing period of tissue damaged by the MI. The work presented here introduces a highly conductive cardiac patch that combines bioresorbable metals and polymers together in a hybrid material structure configured in a thin serpentine geometry that yields elastic mechanical properties. Finite element analysis guides optimized choices of layouts in these systems. Regular and synchronous contraction of human induced pluripotent stem cell‐derived cardiomyocytes on the cardiac patch and ex vivo studies offer insights into the essential properties and the bio‐interface. These results provide additional options in the design of cardiac patches to treat MI and other cardiac disorders.
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