Development of a Novel Bioinspired Fiber Reinforced Hydrogel that Recapitulates Developmental Processes to Regenerate the Bone-Ligament Interface

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This award by the Biomaterials program in the Division of Materials Research to Colorado State University is to study novel biomaterial tissue constructs that will be able to mimic the native interface between soft tissue and bone. This award is cofunded by the Biomedical Engineering program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems. The Global Venture Fund program in the Office of International Science and Engineering is also supporting this project. Although numerous soft-tissue replacement constructs have been developed previously, less attention has been dedicated in recreating the interface between the engineered replacement soft-tissue and the hard bone. The proposed tissue construct will be prepared from a composite hydrogel reinforced with polycaprolactone nanofibers, and seeded by mesenchymal stem cells (MSCs). In order to mimic the structure of native soft tissue-to-bone interface, biochemical and biophysical cues will be modulated along the length of the tissue construct to drive the differentiation of MSCs down the chondrogenic, fibrocartilaginous, and ligamentous pathways. With this design of the tissue graft, the end part of the bone tissue will be established by promoting endochondral ossification of the chondrogenically primed portion of the construct following in vivo implantation of stem cells. This approach is unique and innovative in providing a spatially graded engineered tissue grafts with the capacity to promote the formation of an intermediary soft tissue template, which will differentiate into appropriate end-stage tissue phenotypes in response to local environmental cues. This strategy is to recapitulate different aspects of the developmental process, where all tissues are derived from soft tissue precursors and specific environmental cues are critical to determining end-stage differentiation. With respect to educational and training aspects of the project, this work will involve the training of graduate and undergraduate students in a broad range of innovative tissue engineering and biomaterial design techniques. Student exchanges with Ireland and Northern Ireland are also parts of this project.This project brings together experts from the US, Ireland and Northern Ireland to address a growing problem related to knee injuries using a combined approach that incorporates materials research, engineering, cell biology and biomaterials. Although numerous replacements for injured soft tissue structures have been developed, these techniques typically fail to address the soft tissue-to-bone interface. This interface is necessary for the proper functionality of the entire joint. This project seeks to recreate the interface between soft tissue and bone using a novel biomaterial construct that mimics the structure and function of the native interface. In addition to innovative research, this grant will use outreach activities to emphasize the education of students and the general public. Graduate students and undergraduate students who participate in this research will learn both biological and engineering techniques and will have opportunities to attend conferences to disseminate research and strengthen international collaborations. This work will also provide engineering experience to pre-college students in encouraging their participation in research. Additionally, this project will interact with local Native American communities to encourage their members to participate in science subjects. During National Engineers Week, Girl Scout groups will be involved in lab demonstrations in encouraging younger girls to become interested in science and engineering. Finally, the research will be disseminated to the general public by publishing results in nationally recognized journals.