Gelatin-Based Colloidal Versus Monolithic Gels to Regulate Macrophage-Mediated Inflammatory Response

Area of Science:

• Biomaterials Science
• Immunology
• Tissue Engineering

Background:

• Conventional monolithic hydrogels are elastic, limiting their use as injectable biomaterials.
• Colloidal gels, composed of reversibly assembled particles, exhibit viscoelastic properties like shear-thinning and self-healing, making them suitable for tissue regeneration.
• The immune response to colloidal gels is critical for implant integration but remains understudied.

Purpose of the Study:

• To investigate the in vitro macrophage polarization and in vivo inflammatory response induced by gelatin-based colloidal gels compared to monolithic gels.
• To compare self-healing colloidal gels (pure gelatin or GelMA nanoparticles) with GelMA bulk hydrogels.

Main Methods:

• Investigated in vitro macrophage polarization using gelatin-based colloidal and monolithic hydrogels.
• Assessed in vivo inflammatory response via subcutaneous implantation of colloidal and bulk GelMA hydrogels.
• Analyzed macrophage phenotype (M1/M2) and fibrous capsule formation.

Main Results:

• Hydrogel elasticity, not structure, dominated in vitro macrophage polarization, with stiffer gels inducing pro-inflammatory M2 phenotypes.
• Colloidal gels showed significantly alleviated in vivo immune responses and reduced fibrous capsule formation compared to bulk gels of similar elasticity.
• Improved permeability of colloidal gels may facilitate cell penetration, reducing fibrosis.

Conclusions:

• Colloidal hydrogels demonstrate a less inflammatory profile in vivo compared to monolithic hydrogels.
• Macrophage response is mechanically regulated by hydrogel viscoelasticity, suggesting a design strategy for biomaterials.
• These findings offer insights into biomaterial-host interactions for regenerative medicine and immunotherapy.