Spatial organization of biochemical cues in 3D-printed scaffolds to guide osteochondral tissue engineering
Spatial organization of biochemical cues in 3D-printed scaffolds to guide osteochondral tissue engineering
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DOI：
10.1039/d1bm00859e
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发表时间：
2021-08-26
影响因子：
6.6
通讯作者：
Chow, Lesley W.
中科院分区：
文献类型：
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作者：
Camacho, Paula;Behre, Anne;Chow, Lesley W.
骨软骨（OC）组织的功能性修复仍然具有挑战性，因为从骨到软骨的过渡呈现出关节功能所需的生物化学和物理特性的梯度。骨软骨再生需要恢复天然组织中的空间组成和组织的策略。已经开发了几种生物材料方法来引导人间充质干细胞（hMSCs）的成软骨和成骨分化。这些策略可以与3D打印相结合，3D打印已经成为一种有用的工具，用于生产具有生物活性线索功能化的可调连续支架。然而，功能化通常包括一个或多个制造后处理步骤，这可能导致不希望的副作用，并且通常产生具有均匀分布的化学物质的生物材料。为了解决这些挑战，可以通过溶剂浇铸3D打印肽官能化聚合物在一个步骤中实现表面官能化。合成肽-聚（己内酯）（PCL）缀合物，其带有透明质酸（HA）结合（HAbind-PCL）或矿化（E3-PCL）肽，其已显示分别促进hMSC软骨形成或骨形成。这种3D打印策略能够前所未有地控制连续构建体中的表面肽呈递和空间组织。与不含肽或仅含一种肽的支架相比，同时含有软骨促进肽和骨促进肽的支架具有协同效应，在不存在分化因子的情况下增强了hMSC软骨形成和成骨分化。此外，多肽组织显着影响hMSC的反应。在离散的相对区域中呈现HAbind和E3肽的支架促进hMSC成骨行为。相反，在整个支架中均匀地呈现两种肽促使hMSC向关节和肥大软骨细胞的混合群体分化。这些显著的结果表明hMSC的行为是由双肽呈递和组织驱动的。该平台的下游潜力是能够制造具有空间控制的生化线索的生物材料，以引导功能性组织再生，而不需要分化因子。
Functional repair of osteochondral (OC) tissue remains challenging because the transition from bone to cartilage presents gradients in biochemical and physical properties necessary for joint function. Osteochondral regeneration requires strategies that restore the spatial composition and organization found in the native tissue. Several biomaterial approaches have been developed to guide chondrogenic and osteogenic differentiation of human mesenchymal stem cells (hMSCs). These strategies can be combined with 3D printing, which has emerged as a useful tool to produce tunable, continuous scaffolds functionalized with bioactive cues. However, functionalization often includes one or more post-fabrication processing steps, which can lead to unwanted side effects and often produce biomaterials with homogeneously distributed chemistries. To address these challenges, surface functionalization can be achieved in a single step by solvent-cast 3D printing peptide-functionalized polymers. Peptide-poly(caprolactone) (PCL) conjugates were synthesized bearing hyaluronic acid (HA)-binding (HAbind-PCL) or mineralizing (E3-PCL) peptides, which have been shown to promote hMSC chondrogenesis or osteogenesis, respectively. This 3D printing strategy enables unprecedented control of surface peptide presentation and spatial organization within a continuous construct. Scaffolds presenting both cartilage-promoting and bone-promoting peptides had a synergistic effect that enhanced hMSC chondrogenic and osteogenic differentiation in the absence of differentiation factors compared to scaffolds without peptides or only one peptide. Furthermore, multi-peptide organization significantly influenced hMSC response. Scaffolds presenting HAbind and E3 peptides in discrete opposing zones promoted hMSC osteogenic behavior. In contrast, presenting both peptides homogeneously throughout the scaffolds drove hMSC differentiation towards a mixed population of articular and hypertrophic chondrocytes. These significant results indicated that hMSC behavior was driven by dual-peptide presentation and organization. The downstream potential of this platform is the ability to fabricate biomaterials with spatially controlled biochemical cues to guide functional tissue regeneration without the need for differentiation factors.