Extracellular matrix (ECM) properties, including mechanics, multiscale structure, and bioactive factors, are important regulators of cell behavior, particularly at early stages of bone healing. Such aspects of the ECM modulate an array of cell responses (e.g., cytoskeletal organization, proliferation, migration) for different cells within the bone marrow niche. However, healing of large bone defects may result in delayed or poor bone regeneration. Approaches to mimic these ECM properties are needed for both fundamental studies of cell responses to bone remodeling events and applied studies to promote healing. We hypothesize that engineering synthetic hydrogels to recapitulate aspects of the early stages of healing in healthy bone will promote stem cell invasion and remodeling processes and provide key insights toward studying and improving bone regeneration of traumatic fractures or critical-sized defects. Here, we have created well-defined materials to mimic the mechanical properties, biochemical content, and multiscale structure of native tissues, particularly the collagen-rich environment of the clot-like hematoma formed early in the wound healing process. Specifically, we have synthesized a multifunctional collagen mimetic peptide (mfCMP) that self-assembles into triple helices via the integration of Proline-Hydroxyproline-Glycine repeat units, which are abundant in native collagen. Charged groups encourage further assembly into fibrillar structures, which can then be covalently locked into place within a larger hydrogel scaffold via an alloxycarbonyl reactive handle. Here, we examine mesenchymal stem cell (hMSC) response to these materials for better understanding of cell-matrix interactions toward adaptation to bone healing applications. hMSCs encapsulated within these materials demonstrate high viability (~ 85%) after 10 days of cell culture. At similar timepoints, hMSCs assume unique morphologies in the presence of mfCMPs. Toward studying stem cell invasion, hMSCs were seeded on top of mfCMP hydrogels, demonstrating an affinity for the materials and increased directional migration when a protein gradient was applied to the hydrogel. Ongoing studies of hMSCs within these materials support their relevance for multidimensional cell culture and provide a platform to study cell response in a largely fibrous wound-healing environment and improve upon current bone regeneration techniques.

Incorporating self-assembling hierarchical structures within tunable hydrogel biomaterials to recapitulate aspects of healing bone

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.