Technical: 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.
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.
