Table 1.

Current Methods for Inflammatory Immune Evasion in Material Science

Method	Description	Example Immune Evasive Agent	Ref
Coating material surface with non-fouling substrates
Coating with hydrogels	Hydrogels are known to produce a hydrophilic barrier between the bulk material and cellular medium.	PHEMA PEG	[60]
Immobilization of non-biofouling substances to material surface	Non-biofouling compounds like PEG have been conjugated with peptide mimics of mussel adhesive proteins to facilitate immobilization to a material surface.	PEG-DOPA	[64, 65]
	PEO-like tetraglyme is known to inhibit the deposition of fibrinogen, a mediator of phagocytic response, when adsorbed to the surface of a material.	Tetraglyme	[70, 120, 121]
Coating with microgels	Coating of microgel beads crosslinked with PEG on a PET surface induces a 4-fold decrease in leukocyte adhesion as well as decreases in fibrinogen deposition and MCP-1 concentration over controls.	PEG-pNIPAm	[66–69]
Release of anti-inflammatory drugs
Release of glucocorticoids	Dexamethasone is a known anti-inflammatory that has been used in steroid-eluting stents and pacemaker leads. Has been shown to reduce implant related inflammation.	Dexamethasone	[71–75, 77, 79, 80]
Delivery of pro-wound healing or anti-inflammatory factors
Release of pro-angiogenic factors	VEGF has been released from hydrogels coating glucose sensors to promote angiogenesis.	VEGF	[73, 77, 79, 80]
	bFGF has been delivered via a biodegradable hydrogel to improve limb ischemia via angiogenesis.	bFGF	[81]
Release of pro-inflammatory receptor antagonists	The receptor antagonist for the IL-1 family of cytokines has been delivered for the treatment of rheumatoid arthritis and osteoarthritis. Delivery of both the receptor and the gene encoding the receptor has been studied.	IL-1ra ELP-IL-1ra	[82, 83, 122, 123]
Release of nitric oxide	Activated macrophages produce reactive oxygen and nitrogen intermediates like nitric oxide, which kills bacteria in the surrounding environment. By loading a hydrogel surface with species like nitric oxide, the environment will be free of bacteria, reducing the effect of inflammation.	Nitric oxide	[86–88]
Release of anti-inflammatory cytokines	IL-10 has been delivered for the treatment of a number of inflammatory diseases and is known to down-regulate the synthesis of pro-inflammatory cytokines. Delivery of both the cytokine and the gene encoding the cytokine has been studied.	IL-10	[89–93, 124, 125]
Immobilization of pro-wound healing or anti-inflammatory factors onto material surfaces
Immobilization of erythropoietin	Erythropoietin was immobilized and patterned onto a substrate and its bioactivity was verified by examining the proliferation of a erythropoietin-dependent cell line. Provided impetus for later immobilization studies.	Erythropoietin	[95, 96, 105]
Immobilization of pro-inflammatory receptor antagonists	The receptor antagonist for the IL-1 family of cytokines was immobilized onto a SAM. The modified surface exhibited attenuated inflammatory cytokine production relative to a control.	ELP-IL-1ra	[97]
Immobilization of EGF	EGF has been immobilized in gradients on material surfaces to encourage keratinocyte migration and increased wound healing response.	EGF	[98–101, 104]
Immobilization of bFGF	bFGF has been immobilized onto hydrogel scaffolds and was able to maintain mitogenic and chemotactic activity. Both gradient immobilization and co-immobilization with EGF have been considered.	bFGF	[103, 104]
Immobilization of VEGF	VEGF gradients were immobilized on SAMs to investigate cell migration and potential for inducing angiogenesis. VEGF gradients were found to increase directional migration 2-fold compared to controls.	VEGF	[102]
Cell-based surface modifications
Attachment of adipose-derived stem cells to the surface of an implant	When implanted into rat fat pads, implants elicit a much different immune response than if they were implanted into subcutaneous tissue (more neovascularization, smaller fibrous capsule). Attachment of adipose derived stem cells harvested from fat pads to the surface of an implant promotes neovascularization and small fibrous capsules.	ASCs	[106]