Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, United States.
ACS Appl Mater Interfaces. 2022 Aug 3;14(30):34488-34501. doi: 10.1021/acsami.2c10288. Epub 2022 Jul 21.
Seamlessly integrating soluble factors onto biomedical scaffolds with a precisely manufactured topography for efficient cell control remains elusive since many scaffold fabrication techniques degrade payloads. Surface adsorption of payloads onto synthesized nanoscaffolds retains bioactivity by removing exposure to harsh processing conditions at the expense of inefficient drug loading and uncontrolled release. Herein, we present a nanomaterial composite scaffold paradigm to improve physicochemical surface adsorption pharmacokinetics. As a proof of concept, we integrated graphene oxide (GO) and manganese dioxide (MnO) nanosheets onto nanofibers to increase loading capacity and tune drug release. Non-degradable GO enhances payload retention, while biodegradable MnO enables cell-responsive drug release. To demonstrate the utility of this hybrid nanomaterial scaffold paradigm for tissue engineering, we adsorbed payloads ranging from small molecules to proteins onto the scaffold to induce myogenesis and osteogenesis for multiple stem cell lines. Scaffolds with adsorbed payloads enabled more efficient differentiation than media supplementation using equivalent quantities of differentiation factors. We attribute this increased efficacy to a reverse uptake mechanism whereby payloads are localized around seeded cells, increasing delivery efficiency for guiding differentiation. Additionally, we demonstrate spatial control over cells since differentiation factors are delivered locally through the scaffold. When co-culturing scaffolds with and without adsorbed payloads, only cells seeded on payload-adsorbed scaffolds underwent differentiation. With this modular technology being capable of enhancing multiple differentiation fates for specific cell lines, this technology provides a promising alternative for current tissue engineering scaffolds.
将可溶因子与具有精确制造的拓扑结构的生物医学支架无缝集成，以实现高效的细胞控制，这一目标仍然难以实现，因为许多支架制造技术会降解有效载荷。通过将有效载荷表面吸附到合成纳米支架上，可以避免暴露在苛刻的处理条件下，从而保留生物活性，但这是以药物负载效率低和释放不可控为代价的。在此，我们提出了一种纳米复合材料支架范例，以改善物理化学表面吸附药代动力学。作为概念验证，我们将氧化石墨烯 (GO) 和二氧化锰 (MnO) 纳米片整合到纳米纤维上，以提高载药量并调节药物释放。不可降解的 GO 增强了有效载荷的保留，而可生物降解的 MnO 则实现了细胞响应性药物释放。为了证明这种混合纳米材料支架范例在组织工程中的实用性，我们将从小分子到蛋白质的各种有效载荷吸附到支架上，以诱导多种干细胞系的肌生成和骨生成。与使用等量分化因子的培养基补充相比，具有吸附有效载荷的支架可实现更有效的分化。我们将这种增强的功效归因于一种反向摄取机制，其中有效载荷被定位在接种细胞周围，从而提高了用于指导分化的递送效率。此外，我们证明了对细胞的空间控制，因为分化因子通过支架局部递送。在共培养具有和不具有吸附有效载荷的支架时，只有在吸附有效载荷的支架上接种的细胞才会发生分化。由于这种模块化技术能够增强特定细胞系的多种分化命运，因此它为当前的组织工程支架提供了一种有前途的替代方案。
