Table 2.

Summary of scaffolds used in immunomodulation studies, their modification methods, and immune response to them.

Materials Used in Scaffold Fabrication	Modification Method	Immune Response	References
Chitosan	Integrating magnetic ferrite nanoparticles and lanthanum into hydroxyapatite.	The modification recruited MSCs at the implant site, leading to the promotion of an anti-inflammatory phenotype among macrophages and immune cells.	[135]
Laponite	Seeding with BMSCs	Cell seeding demonstrated a remarkable ability to shift macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype.	[139]
Silk fibroin scaffold loaded with graphene oxide and nanohydroxyapatite	Seeding with urine-derived MSCs	Six weeks post-implantation in calvarial bone, a significant upswing in CD206 expression was noted, signifying an increased prevalence of M2-type macrophages.	[140]
Chitin, nano-hydroxyapatite, and poly(ε-caprolactone)	Incorporation of MSCs	Gene expression analysis revealed a balanced expression of genes associated with both M1 macrophage polarization and M2 macrophage polarization after implantation.	[141]
Electrospun silk fibroin scaffolds	Seeding with IFN-γ stimulated MSCs	They demonstrated that MSCs cultured on silk fibroin constructs significantly reduced TNF-α secretion from lipopolysaccharide-activated murine splenocytes.	[143]
Polyethylene glycol (PEG) hydrogel	MSC encapsulation	Cell loading significantly dampened the foreign body response to fibroblast cell-incorporated hydrogels. They noted that the osteogenic differentiation of these cells diminished their capacity to modulate inflammation. Additionally, they identified prostaglandin E2 (PGE2) as a mediator of MSC immunomodulation of macrophages.	[145]
3D porous collagen and collagen/chitosan scaffolds	Incorporation of synovial fluid MSCs	Cell loading resulted in increased expression of master gene regulators associated with the suppression of chronic inflammation.	[146]
Injectable hydrogels derived from the decellularized ECM	Incorporation of urine-derived MSCs.	In a rat model of cartilage defects, the cell-laden hydrogels demonstrated remarkable capabilities, including the stimulation of ECM secretion, modulation of the immune response, and promotion of cartilage regeneration.	[147]
Collagen	Incorporation of MSCs	Three-dimensional scaffolds, such as hydrogels and sponges, notably heightened the expression of mRNA and the production of proteins associated with immunomodulation, surpassing conventional two-dimensional setups.	[149]
3D collagen scaffold	BMSC seeding	Following transplantation, they observed a significant reduction in inflammatory cytokines (TNF-a, IL-1b, and IL-6), correlating with enhanced axonal regeneration in spinal cord injury.	[151]
PLGA scaffold	Seeding with TNF-α-primed MSCs	The construct reduced production of the inflammatory factor IL-1α and influenced macrophage polarization.	[152]
PLGA scaffold	Seeding with Amniotic Epithelial Stem Cells	These constructs enhanced the immunomodulatory activity of the cells, which was linked to the activation of the mechanotransducer YAP.	[153]
Polydopamine bioceramics	Mussel surface coatings	This nanopattern significantly augmented ASC’s ability to modulate the immune response, fostering anti-inflammatory effects and curbing immune cell activation.	[158]
Decellularized ECM	MSC loading	Both MSCs and the decellularized ECM scaffold exhibited the ability to promote macrophage polarization toward the M2 phenotype while inhibiting polarization toward the M1 phenotype.	[159]
Decellularized pericardial scaffold filled with a peptide hydrogel	Loading with porcine cardiac ASC-derived extracellular vesicles	The developed scaffolds mitigated adverse remodeling processes and showed anti-inflammatory effects.	[160]
Cardiac extracellular matrix	MSCs loading	MSCs seeded onto the ECM significantly modulated inflammatory responses.	[161]
Porcine cardiac ECM	No modifications	These scaffolds underwent vascularization and bolstered regenerative remodeling, as indicated by an elevated proportion of M2/M1 macrophage phenotype at the site of injury.	[162]
Polyethyleneimine-modified polycaprolactone fibers	Surface coating with MSCs-derived exosomes	Exosomes predominantly interacted with CD68+ macrophages rather than CD3+ T cells. The scaffolds induced the accumulation of immunomodulatory M2-like macrophages.	[15]