Implantable
hydrogels are designed to treat wounds by providing
structure and delivering additional cells to damaged tissue. These
materials must consider how aspects of the native wound, including
environmental chemical cues, affect and instruct delivered cells.
One cell type researchers are interested in delivering are human mesenchymal
stem cells (hMSCs) due to their importance in healing. Wound healing
involves recruiting and coordinating a variety of cells to resolve
a wound. hMSCs coordinate the cellular response and are signaled to
the wound by cytokines, including transforming growth factor-β
(TGF-β) and tumor necrosis factor-α (TNF-α), present in vivo. These cytokines change hMSC secretions, regulating
material remodeling. TGF-β, present from inflammation through
remodeling, directs hMSCs to reorganize collagen, increasing extracellular
matrix (ECM) structure. TNF-α, present primarily during inflammation,
cues hMSCs to clear debris and degrade ECM. Because cytokines change
how hMSCs degrade their microenvironment and are naturally present
in the wound, they also affect how hMSCs migrate out of the scaffold
to conduct healing. Therefore, the effects of cytokines on hMSC remodeling
are important when designing materials for cell delivery. In this
work, we encapsulate hMSCs in a polymer–peptide hydrogel and
incubate the scaffolds in media with TGF-β or TNF-α at
concentrations similar to those in wounds. Multiple particle tracking
microrheology (MPT) measures hMSC-mediated scaffold degradation in
response to these cytokines, which mimics aspects of the in
vivo microenvironment post-implantation. MPT uses video microscopy
to measure Brownian motion of particles in a material, quantifying
structure and rheology. Using MPT, we measure increased hMSC-mediated
remodeling when cells are exposed to TNF-α and decreased remodeling
after exposure to TGF-β when compared to untreated hMSCs. This
agrees with previous studies that measure: (1) TNF-α encourages
matrix reorganization and (2) TGF-β signals the formation of
new matrix. These results enable material design that anticipates
changes in remodeling after implantation, improving control over hMSC
delivery and healing.
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