Authors
Jiye Lee, University of Illinois Urbana Champaign
Jiachun Shi, University of Illinois at Urbana-Champaign
Musculoskeletal injuries affect large populations worldwide, and many existing treatments fail to restore functional tissue or are not scalable for large populations. Instructive biomaterials along with cell therapy and drug cues can promote tissue regeneration by retaining and signaling mesenchymal stem cells (MSC) differentiation. In this work, we aim to modify collagen scaffolds to control the local microenvironment by injecting cell and drug fused hydrogels into the porous scaffold to support MSC differentiation, enhance cell deposition, and promote vascular formation. Pore size and directionality of scaffolds are tuned to mimic tissue structures using freeze-drying strategies. We hypothesized that delivery challenges associated with lyophilized porous scaffolds could be improved by printing biomolecule-laden hydrogels into the porous scaffold after rehydration. MSC-infused Thiolated Gelatin (GelSH) or Maleimide Gelatin (GelMAL) hydrogels were 3D printed after ink calibration and rheological characterization. Flow properties of both materials show the existence of yield stresses, and therefore shear thinning behavior, which is desirable for printing. While GelMAL construct remained stable for longer periods at basal temperatures after printing, GelSH hydrogels exhibited earlier cell release due to weaker crosslinking. Current work is studying cell migration from the hydrogel to the surrounding collagen scaffold. We expect that while lower number of cells are seeded using a 3D printing method, local material properties can be more precisely controlled. Further, we seek to improve poor vascular integration of biomaterials that has hindered their potential to be a scalable solution for musculoskeletal injuries. Deferoxamine (DFO), has been associated with upregulation of angiogenic markers such HIF-1a and VEGF, making it a promising angiogenic stimulator. Here, DFO-PEG microgels were fabricated via batch emulsion, loaded into collagen suspension, and freeze dried to form collagen porous scaffolds. We expect DFO-PEG microgels to remain in collagen scaffolds longer than free loaded DFO, while bulk mechanical properties are not significantly affected. We are measuring patterns of MSC gene expression and metabolic activity in response to DFO as well as its potential to support vascular structure formation. Materials that facilitate vasculature integration and induce tissue regenerative responses offer significant innovation. These projects will advance multimaterial design strategies to create biomaterials for musculoskeletal tissue engineering.
