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.

中文翻译：

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3D 打印支架中生化线索的空间组织以指导骨软骨组织工程

骨软骨 (OC) 组织的功能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化和物理特性梯度。骨软骨再生需要恢复在天然组织中发现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指导人类间充质干细胞 (hMSC) 的软骨形成和成骨分化。这些策略可以与 3D 打印相结合，3D 打印已成为生产具有生物活性线索功能化的可调连续支架的有用工具。然而，功能化通常包括一个或多个制造后处理步骤，这可能会导致不需要的副作用，并且通常会产生化学分布均匀的生物材料。为了应对这些挑战，可以通过溶剂浇铸 3D 打印肽功能化聚合物一步实现表面功能化。合成了带有透明质酸 (HA) 结合 (HAbind-PCL) 或矿化 (E3-PCL) 肽的肽-聚（己内酯）（PCL）偶联物，它们已被证明分别促进 hMSC 软骨形成或成骨。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。与没有肽或只有一种肽的支架相比，同时提供软骨促进肽和骨促进肽的支架具有协同作用，在没有分化因子的情况下增强了 hMSC 的软骨形成和成骨分化。此外，多肽组织显着影响 hMSC 反应。在离散的相对区域中呈递 HAbind 和 E3 肽的支架促进了 hMSC 的成骨行为。相比之下，在整个支架中均匀呈递两种肽会促使 hMSC 向关节和肥大软骨细胞的混合群体分化。这些重要结果表明 hMSC 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生化线索的生物材料，以指导功能性组织再生，而无需分化因子。在整个支架中均匀呈递两种肽促使 hMSC 向关节和肥大软骨细胞的混合群体分化。这些重要结果表明 hMSC 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生化线索的生物材料，以指导功能性组织再生，而无需分化因子。在整个支架中均匀呈递两种肽促使 hMSC 向关节和肥大软骨细胞的混合群体分化。这些重要结果表明 hMSC 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生化线索的生物材料，以指导功能性组织再生，而无需分化因子。