Kong Hyun Joon, Smith Molly K, Mooney David J
Department of Biologic and Materials Sciences, University of Michigan, Dental 5213, 1011 N University Avenue, Ann Arbor, MI 48109-1078, USA.
Biomaterials. 2003 Oct;24(22):4023-9. doi: 10.1016/s0142-9612(03)00295-3.
Hydrogel-forming materials have been widely utilized as an immobilization matrix and transport vehicle for cells. Success in these applications is dependent upon maintaining cell viability through the gel preparation process. We hypothesized that the high viscosity of pre-gelled solutions typically used in these applications may decrease cell viability due to the high shear forces required to mix cells with these solutions. Further, we proposed this harmful effect could be mediated by decreasing the molecular weight (Mw) of the polymer used to form the gel, while maintaining its gel-forming ability. To investigate this hypothesis, alginate was used as model system, as this copolymer consists of cross-linkable guluronic acid (G) blocks and non-cross-linkable blocks. Decreasing the Mw of alginate using irradiation (e.g., irradiating at dose of 2 Mrad) decreased the low shear viscosity of 2% (w/w) pre-gelled solutions from 1000 to 4 cP, while maintaining high elastic moduli, once cross-linked to form a gel. Importantly, the immobilization of cells with these polymer hydrogels increased cell viability from 40% to 70%, as compared to using high Mw polymer chains to form the gels. Furthermore, the solids concentration of gels formed with the low Mw alginate could be raised to further increase the moduli of gels without significantly deteriorating the viability of immobilized cells. This was likely due to the limited increase in the viscosity of these solutions. This material design approach may be useful with a variety of synthetic or naturally occurring block copolymers used to immobilize cells.
水凝胶形成材料已被广泛用作细胞的固定化基质和运输载体。这些应用的成功取决于在凝胶制备过程中保持细胞活力。我们假设，这些应用中通常使用的预凝胶溶液的高粘度可能会由于将细胞与这些溶液混合所需的高剪切力而降低细胞活力。此外，我们提出这种有害影响可以通过降低用于形成凝胶的聚合物的分子量（Mw）来介导，同时保持其凝胶形成能力。为了研究这一假设，使用藻酸盐作为模型系统，因为这种共聚物由可交联的古洛糖醛酸（G）嵌段和不可交联的嵌段组成。使用辐射（例如，以2兆拉德的剂量辐照）降低藻酸盐的Mw，可将2%（w/w）预凝胶溶液的低剪切粘度从1000厘泊降低到4厘泊，同时在交联形成凝胶后保持高弹性模量。重要的是，与使用高Mw聚合物链形成凝胶相比，用这些聚合物水凝胶固定细胞可使细胞活力从40%提高到70%。此外，用低Mw藻酸盐形成的凝胶的固体浓度可以提高，以进一步增加凝胶的模量，而不会显著降低固定化细胞的活力。这可能是由于这些溶液的粘度增加有限。这种材料设计方法可能适用于用于固定细胞的各种合成或天然存在的嵌段共聚物。
