Barthold Jeanne E, McCreery Kaitlin P, Martinez Jaylene, Bellerjeau Charlotte, Ding Yifu, Bryant Stephanie J, Whiting Gregory L, Neu Corey P
Paul M Rady Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, United States of America.
Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, United States of America.
Biofabrication. 2022 Mar 16;14(2). doi: 10.1088/1758-5090/ac584c.
Articular cartilage is a layered tissue with a complex, heterogeneous structure and lubricated surface which is challenging to reproduce using traditional tissue engineering methods. Three-dimensional printing techniques have enabled engineering of complex scaffolds for cartilage regeneration, but constructs fail to replicate the unique zonal layers, and limited cytocompatible crosslinkers exist. To address the need for mechanically robust, layered scaffolds, we developed an extracellular matrix particle-based biomaterial ink (pECM biomaterial ink) which can be extruded, polymerizes via disulfide bonding, and restores layered tissue structure and surface lubrication. Our cartilage pECM biomaterial ink utilizes functionalized hyaluronan (HA), a naturally occurring glycosaminoglycan, crosslinked directly to decellularized tissue particles (ø40-100m). We experimentally determined that HA functionalized with thiol groups (t-HA) forms disulfide bonds with the ECM particles to form a 3D network. We show that two inks can be co-printed to create a layered cartilage scaffold with bulk compressive and surface (friction coefficient, adhesion, and roughness) mechanics approaching values measured on native cartilage. We demonstrate that our printing process enables the addition of macropores throughout the construct, increasing the viability of introduced cells by 10%. The delivery of these 3D printed scaffolds to a defect is straightforward, customizable to any shape, and adheres to surrounding tissue.
关节软骨是一种具有复杂、异质结构和润滑表面的分层组织，使用传统组织工程方法进行复制具有挑战性。三维打印技术能够制造用于软骨再生的复杂支架，但构建物无法复制独特的分层结构，且细胞相容性交联剂有限。为满足对机械坚固的分层支架的需求，我们开发了一种基于细胞外基质颗粒的生物材料墨水（pECM生物材料墨水），它可以挤出，通过二硫键聚合，并恢复分层组织结构和表面润滑性。我们的软骨pECM生物材料墨水利用功能化透明质酸（HA），一种天然存在的糖胺聚糖，直接交联到脱细胞组织颗粒（ø40 - 100m）上。我们通过实验确定，用硫醇基团功能化的HA（t - HA）与ECM颗粒形成二硫键以形成三维网络。我们表明，可以共打印两种墨水以创建具有整体压缩和表面（摩擦系数、粘附力和粗糙度）力学性能接近天然软骨测量值的分层软骨支架。我们证明，我们的打印过程能够在整个构建物中添加大孔，使引入细胞的活力提高10%。将这些三维打印支架递送至缺损部位很简单，可定制成任何形状，并能粘附于周围组织。
