Department of Bioengineering, Lehigh University, Bethlehem, PA, USA.
Integrated Degree in Engineering, Arts, and Sciences Program, Lehigh University, Bethlehem, PA, USA.
Biomater Sci. 2021 Oct 12;9(20):6813-6829. doi: 10.1039/d1bm00859e.
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.
骨软骨（OC）组织的功能修复仍然具有挑战性，因为从骨到软骨的转变呈现出必要的生化和物理特性的梯度，这些特性对于关节功能至关重要。骨软骨再生需要采用能够恢复天然组织中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骨髓间充质干细胞（hMSC）的软骨生成和成骨分化。这些策略可以与 3D 打印相结合，3D 打印已成为一种有用的工具，可以生产具有生物活性线索的可调谐、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，这可能导致不必要的副作用，并且通常会产生具有均匀分布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 打印肽功能化聚合物来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）缀合物，这些肽已被证明分别促进 hMSC 软骨生成或成骨。这种 3D 打印策略能够在连续结构内以前所未有的方式控制表面肽的呈现和空间组织。与没有肽或只有一种肽的支架相比，呈现出既促进软骨又促进骨的肽的支架具有协同作用，能够在没有分化因子的情况下增强 hMSC 的软骨生成和成骨分化。此外，多肽组织对 hMSC 反应有显著影响。在离散的相反区域呈现 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现两种肽会促使 hMSC 分化为混合的关节和肥大软骨细胞群体。这些显著的结果表明，hMSC 的行为是由双肽呈现和组织决定的。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，以引导功能性组织再生，而无需分化因子。
