Modulating Macrophage Response with Microporous Annealed Particle Scaffolds

dc.contributor.advisor

Segura, Tatiana TS

dc.contributor.author

Liu, Yining

dc.date.accessioned

2023-03-28T21:41:02Z

dc.date.issued

2022

dc.department

Biomedical Engineering

dc.description.abstract

When designing biomaterials for clinical applications, the performance of these platforms hinges on their interaction with the host immune system. A failure in engaging and incorporating the correct immune response would lead to foreign body response and subsequent rejection of the materials. To improve the biocompatibility of biomaterials and avoid undesired immune reactions, the key immunomodulatory cell type macrophage needs to be engaged and its phenotype modulated properly and timely. Therefore, the design parameters of biomaterials should be carefully considered in the context of macrophage modulation. Microporous annealed particle scaffolds (MAPS) are a new class of immunomodulatory granular materials generated through the interlinking of microgels. The modular nature of MAPS offers enormous tunability in not only the individual microgel design but also the homogenous or heterogenous microgel assembly into the bulk scaffold. We leveraged the plug-and-play feature of MAPS to study the effect of two design parameters, microgel crosslinking peptide (comprised of L- or D-amino acids) and spatial confinement (achieved through varying microgel size), on macrophage modulation and host responses. We uncovered that a fine balance between pro-regenerative and pro-inflammatory macrophage phenotypes in MAPS with D-amino acid-based crosslinker was an indicator for regenerative scaffolds in a subcutaneous implantation model. We also discovered that scaffolds comprised of large microgels with pore size that can accommodate ~40 µm diameter spheres induced a more balanced pro-regenerative macrophage response and better wound healing outcomes with more mature collagen regeneration and reduced inflammation level. The role of spatial confinement on macrophage response was further explored in vitro, where we demonstrated that size-dependent macrophage response to M1/M2 cytokine stimulations was tied to the change in cell morphology and motility. This work offers valuable insights into the dynamic immune response to synthetic porous scaffolds with a specific focus on macrophages, and establishes a foundation for further optimization of immunomodulatory pro-regenerative outcomes for would healing and biomaterial implants.

dc.identifier.uri

https://hdl.handle.net/10161/26792

dc.subject

Biomedical engineering

dc.subject

Biomaterial

dc.subject

Foreign body response

dc.subject

Granular material

dc.subject

Immune modulation

dc.subject

Macrophage

dc.subject

Wound healing

dc.title

Modulating Macrophage Response with Microporous Annealed Particle Scaffolds

dc.type

Dissertation

duke.embargo.months

22

duke.embargo.release

2025-01-27T00:00:00Z

Files

Collections