Biomimetic Tissue Analogs via Micropatterned Deposition of Proteins

ID：MPS/DMR/BMAT（7623）1306665 PI：阿库斯、奥赞 ORG：Case Western ReserveTitle：通过蛋白质的微图案化沉积的仿生组织类似物技术：制造机械上坚固的生物材料，同时具有足够的孔隙率用于细胞和血管渗透仍然是一个主要的挑战，特别是在承重肌肉骨骼组织的工程中。 这项拟议的研究将通过使用微图案电极对富含胶原蛋白的蛋白质溶液进行电化学压实（ELC）而具有突破性，从而为设计具有受控尺寸和分布的孔阵列创造条件。 ELC的效用将在肌腱修复支架的制作方面进行评估。 第一目标研究将提供关于基质各向异性和基质模量（在MPa至GPa的范围内）对脂肪组织来源的间充质干细胞（aMSC）的分化和基质沉积的影响的基本见解。 通过在基质中包括硫酸皮肤素（DS）（一种富含肌腱的糖胺聚糖）来补充地形分化线索。 被确定为最有利于所需细胞反应的材料配方将用于第二阶段研究，在此期间，CAD，CAM和FEM等关键技术将共同用于设计最佳晶格微观形态，从而产生强大的宏观机械功能。 将使用计算机控制的制造方法制造计算上有价值的支架结构，并将其细胞化以在3D环境中筛选细胞反应。 非技术：肌腱退化，特别是与肩部衰老有关的肌腱退化，是一个普遍的健康问题，影响着数十万人，并给经济带来了巨大的负担。 缺乏机械上坚固的支架来修复肌腱，并且大多数生物材料被用作损伤肌腱上的加固补片。 所提出的图案沉积技术提供了一种可行的替代方案，作为再生肌腱的3D生物活性框架。 这有可能改善目前的治疗方式。 拟议的研究还将开发一种可扩展到其他组织（如骨骼、韧带、肝脏和血管结构）的技术。 相互连接的受控孔隙空间的图案化沉积允许增强的质量输送，为工程化更大的组织体积创造机会。 所提出的研究的优点之一是理解基质各向异性和基质刚度在诱导骨髓源性干细胞在没有生长因子的情况下成为肌腱细胞中的相对作用。 通过机械成分线索实现分化是非常重要的，因为生长因子是昂贵的并且受到严格的调控。 拟议项目的外展部分将通过跨学科的高级设计团队和研究参与，培养本科生对脚手架设计和制造的兴趣。 本科生将通过以下方式接触新兴的生物制造领域：（a）为项目的每一年提供一名本科生（全日制夏季），以及（B）指导高级设计团队关于拟议活动的主题。新兴的生物制造领域在新经济中非常重要，拟议的活动旨在激励未来的创新者。

ID: MPS/DMR/BMAT(7623) 1306665 PI: Akkus, Ozan ORG: Case Western ReserveTitle: Biomimetic Tissue Analogs via Micropatterned Deposition of ProteinsTechnical: Fabrication of mechanically robust biomaterials that also possess sufficient porosity for cell and blood vessel penetration remains a major challenge, particularly in engineering of load bearing musculoskeletal tissues. The proposed research will be groundbreaking through electrochemical-compaction (ELC) of collagen-rich protein solution using micropatterned electrodes, thus creating the provision for designing arrays of pores with controlled size and distribution. The utility of ELC will be assessed in terms of fabricating scaffolds for tendon repair. First aim studies will provide fundamental insight on the effects of matrix anisotropy and matrix modulus (in a range of MPa to GPa) on differentiation and matrix deposition by adipose tissue-derived mesenchymal stem cells (aMSCs). The topographical differentiation cues will be supplemented with compositional cues by including dermatan sulfate (DS), a glycosaminoglycan richly present in tendon, in the matrix. That material formulation determined to be the most conducive to desired cell response will be used in second phase studies during which key technologies such as CAD, CAM and FEM will be used collectively to design for optimal lattice micromorphology resulting in robust macroscale mechanical function. Computationally meritorious scaffold structures will be fabricated using computer controlled fabrication methods and cellularized to screen cell response in the 3D environment. Non-Technical: Tendon degeneration, particularly those associated with aging at the shoulder, is a widespread health problem that is affecting hundreds of thousands and imposing a substantial burden on the economy. There is a lack of mechanically robust scaffolds to repair tendon, and most biomaterials are applied as reinforcement patches over the injured tendon. The proposed pattern deposition technology presents a viable alternative as a 3D bioactive framework to regenerate tendons. This carries the potential to improve the current treatment modalities. The proposed research will also develop an enabling technology that can be extended to other tissues such as bone, ligament, liver, and vascular structures. Patterned deposition of interconnected controlled pore space allows for enhanced mass-transport, creating the opportunity for engineering larger tissue volumes. One of the merits of the proposed studies is understanding the relative roles of matrix anisotropy and matrix stiffness in inducing marrow-derived stem cells to become tendon cells in the absence of growth factors. Achievement of differentiation by mechano-compositional cues is highly significant, because growth factors are expensive and heavily regulated. The outreach component of the proposed project will foster undergraduate students' interests in scaffold design and fabrication through interdisciplinary senior design teams and research engagement. Undergraduate students will be exposed to the emerging field of biofabrication by: (a) accommodating one undergraduate student (full-time summer) for each year of the project, and (b) mentoring senior design teams on topics that map to the proposed activities. The emerging field of biofabrication is important in the new economy, and the proposed activities aim to inspire the innovators of the future.