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Cell-derived extracellular matrix (ECM) has become increasingly popular in tissue engineering applications due to its ability to provide tailored signals for desirable cellular responses. Anisotropic cardiac-specific ECM scaffold decellularized from human induced pluripotent stem cell (hiPSC)-derived cardiac fibroblasts (hiPSC-CFs) mimics the native cardiac microenvironment and provides essential biochemical and signaling cues to hiPSC-derived cardiomyocytes (hiPSC-CMs). The objective of this study was to assess the efficacy of two detergent-based decellularization methods: (1) a combination of ethylenediaminetetraacetic acid and sodium dodecyl sulfate (EDTA + SDS) and (2) a combination of sodium deoxycholate and deoxyribonuclease (SD + DNase), in preserving the composition and bioactive substances within the aligned ECM scaffold while maximumly removing cellular components. The decellularization effects were evaluated by characterizing the ECM morphology, quantifying key structural biomacromolecules, and measuring preserved growth factors. Results showed that both treatments met the standard of cell removal (less than 50 ng/mg ECM dry weight) and substantially preserved major ECM biomacromolecules and growth factors. The EDTA + SDS treatment was more time-efficient and has been determined to be a more efficient method for generating an anisotropic ECM scaffold from aligned hiPSC-CFs. Moreover, this cardiac-specific ECM has demonstrated effectiveness in supporting the alignment of hiPSC-CMs and their expression of mature structural and functional proteins in in vitro cultures, which is crucial for cardiac tissue engineering. [ABSTRACT FROM AUTHOR]

A healthy lymphatic system is required to return excess interstitial fluid back to the venous circulation. However, up to 49% of breast cancer survivors eventually develop breast cancer-related lymphedema due to lymphatic injuries from lymph node dissections or biopsies performed to treat cancer. While early-stage lymphedema can be ameliorated by manual lymph drainage, no cure exists for late-stage lymphedema when lymph vessels become completely dysfunctional. A viable late-stage treatment is the autotransplantation of functional lymphatic vessels. Here we report on a novel engineered lymphatic flap that may eventually replace the skin flaps used in vascularized lymph vessel transfers. The engineered flap mimics the lymphatic and dermal compartments of the skin by guiding multi-layered tissue organization of mesenchymal stem cells and lymphatic endothelial cells with an aligned decellularized fibroblast matrix. The construct was tested in a novel bilayered wound healing model and implanted into athymic nude rats. The in vitro model demonstrated capillary invasion into the wound gaps and deposition of extracellular matrix fibers, which may guide anastomosis and vascular integration of the graft during wound healing. The construct successfully anastomosed in vivo, forming chimeric vessels of human and rat cells. Overall, our flap replacement has high potential for treating lymphedema. [ABSTRACT FROM AUTHOR]