Ameer Guillermo, Keate Rebecca, Bury Matthew, Mendez-Santos Maria, Gerena Andres, Goedegebuure Madeleine, Rivnay Jonathan, Sharma Arun
Res Sq. 2024 Jan 29:rs.3.rs-3817836. doi: 10.21203/rs.3.rs-3817836/v1.
Tissue engineering heavily relies on cell-seeded scaffolds to support the complex biological and mechanical requirements of a target organ. However, in addition to safety and efficacy, translation of tissue engineering technology will depend on manufacturability, affordability, and ease of adoption. Therefore, there is a need to develop scalable biomaterial scaffolds with sufficient bioactivity to eliminate the need for exogenous cell seeding. Herein, we describe synthesis, characterization, and implementation of an electroactive biodegradable elastomer for urinary bladder tissue engineering. To create an electrically conductive and mechanically robust scaffold to support bladder tissue regeneration, we developed a phase-compatible functionalization method wherein the hydrophobic conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) was polymerized within a similarly hydrophobic citrate-based elastomer poly(octamethylene-citrate-co-octanol) (POCO) film. We demonstrate the efficacy of this film as a scaffold for bladder augmentation in athymic rats, comparing PEDOT-POCO scaffolds to mesenchymal stromal cell-seeded POCO scaffolds. PEDOT-POCO recovered bladder function and anatomical structure comparably to the cell-seeded POCO scaffolds and significantly better than non-cell seeded POCO scaffolds. This manuscript reports: (1) a new phase-compatible functionalization method that confers electroactivity to a biodegradable elastic scaffold, and (2) the successful restoration of the anatomy and function of an organ using a cell-free electroactive scaffold.
组织工程严重依赖于接种细胞的支架来满足目标器官复杂的生物学和力学需求。然而,除了安全性和有效性之外,组织工程技术的转化还将取决于可制造性、可承受性和易用性。因此,需要开发具有足够生物活性的可扩展生物材料支架,以消除对外源细胞接种的需求。在此,我们描述了一种用于膀胱组织工程的电活性可生物降解弹性体的合成、表征及应用。为了创建一个导电且机械性能稳健的支架来支持膀胱组织再生,我们开发了一种相兼容的功能化方法,其中疏水性导电聚合物聚(3,4-乙撑二氧噻吩)(PEDOT)在同样疏水性的基于柠檬酸盐的弹性体聚(辛亚甲基柠檬酸盐-共-辛醇)(POCO)薄膜内聚合。我们将PEDOT-POCO支架与接种间充质基质细胞的POCO支架进行比较,证明了该薄膜作为无胸腺大鼠膀胱扩大术支架的有效性。PEDOT-POCO恢复膀胱功能和解剖结构的效果与接种细胞的POCO支架相当,且明显优于未接种细胞的POCO支架。本论文报道了:(1)一种赋予可生物降解弹性支架电活性的新的相兼容功能化方法,以及(2)使用无细胞电活性支架成功恢复器官的解剖结构和功能。