School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
Henry Royce Institute, University of Manchester, Manchester, United Kingdom.
Biofabrication. 2024 Oct 24;17(1):015005. doi: 10.1088/1758-5090/ad8379.
Intervertebral disc (IVD) function is achieved through integration of its two component regions: the nucleus pulposus (NP) and the annulus fibrosus (AF). The NP is soft (0.3-5 kPa), gelatinous and populated by spherical NP cells in a polysaccharide-rich extracellular matrix (ECM). The AF is much stiffer (∼100 kPa) and contains layers of elongated AF cells in an aligned, fibrous ECM. Degeneration of the disc is a common problem with age being a major risk factor. Progression of IVD degeneration leads to chronic pain and can result in permanent disability. The development of therapeutic solutions for IVD degeneration is impaired by a lack ofmodels of the disc that are capable of replicating the fundamental structure and biology of the tissue. This study aims to investigate if a newly developed suspended hydrogel bioprinting system (termed SLAM) could be employed to fabricate IVD analogues with integrated structural and compositional features similar to native tissue. Bioprinted IVD analogues were fabricated to recapitulate structural, morphological and biological components present in the native tissue. The constructs replicated key structural components of native tissue with the presence of a central, polysaccharide-rich NP surrounded by organised, aligned collagen fibres in the AF. Cell tracking, actin and matrix staining demonstrated that embedded NP and AF cells exhibited morphologies and phenotypes analogous to what is observedwith elongated, aligned AF cells and spherical NP cells that deposited HA into the surrounding environment. Critically, it was also observed that the NP and AF regions contained a defined cellular and material interface and segregated regions of the two cell types, thus mimicking the highly regulated structure of the IVD.
椎间盘(IVD)的功能是通过其两个组成区域的整合来实现的:髓核(NP)和纤维环(AF)。NP 是柔软的(0.3-5 kPa),凝胶状的,由富含多糖的细胞外基质(ECM)中的球形 NP 细胞组成。AF 则硬得多(∼100 kPa),并包含排列在纤维 ECM 中的拉长的 AF 细胞层。椎间盘的退化是一个常见的问题,年龄是一个主要的危险因素。IVD 退化的进展导致慢性疼痛,并可能导致永久性残疾。由于缺乏能够复制组织基本结构和生物学的椎间盘模型,因此对 IVD 退化的治疗解决方案的开发受到了阻碍。本研究旨在探讨新开发的悬浮水凝胶生物打印系统(称为 SLAM)是否可用于制造具有类似于天然组织的集成结构和组成特征的 IVD 类似物。生物打印的 IVD 类似物被制造出来以重现天然组织中存在的结构、形态和生物学成分。构建物复制了天然组织的关键结构成分,其中存在一个中央、富含多糖的 NP,周围是 AF 中排列整齐的胶原纤维。细胞跟踪、肌动蛋白和基质染色表明,嵌入的 NP 和 AF 细胞表现出与拉长的、排列整齐的 AF 细胞和将 HA 沉积到周围环境中的球形 NP 细胞类似的形态和表型。关键的是,还观察到 NP 和 AF 区域包含一个定义明确的细胞和材料界面,并分隔了两种细胞类型的区域,从而模拟了 IVD 的高度调节结构。