Table 1.

Key Examples of Materials for Immune Engineering

	Approach	Biomaterial	Notes	Refs
Intrinsic immunogenicity	Polymer particles	Poly(D,L-lactic-co-glycolic acid)	T cell stimulation is shape dependent	[16,18]
		Gold NPs	Particle shape and hydrophobicity alter cytokine secretion profiles	[23,99]
		Polystyrene	Ellipsoidal particles improve pharmacokinetics by enhancing circulation time, while smaller particles are taken up more efficiently by pulmonary APCs	[17,21,22]
		Poly(β-amino esters)	The immunogenicity of polymers changes during degradation	[27,28]
	Liposomes		Ellipsoid liposomes exhibit improved pharmacokinetics compared with spheres	[17]
	Self-assembly	Poly(methacrylic acid)	Different immune cell types preferentially interact with distinctly shaped particles	[19]
		Peptide nanofibers	Negatively charged surfaces prevent uptake by APCs to limit adaptive immune response	[25]
	Porous particles	Silicon	Surface chemistry of particles changes immunostimulatory effects	[24]
Infectious disease	Polymer particles	Poly(D,L-lactic-co-glycolic acid)	PLGA encapsulation increases uptake of cargo by APCs and allows for controlled release	[29,35,41,8]
		Poly(D,L-lactic-co-glycolic acid)-b- poly(L-histidine)-b-poly(ethylene glycol)	Particulate delivery of antigen can change the immune response from tolerogenic to long-lived protection	[49]
	Liposomes		Encapsulating cargo into liposomes increases retention time in the draining LN for increased interaction with T cells, yields control over protein density, and can be attached to T cells for targeted delivery	[30,31,39,40]
	Porous particles	Poly(vinyl pyrrolidone)	Porous particles increase the diffusion of intracellular proteases leading to faster and more efficient processing and increase the surface area allowing for increased cargo loading density	[32]
		Silicon	Co-delivering signals in porous particles synergistically increases cytokine secretion	[33]
	Self-assembly	Peptide and TLRa	Self-assembling immune signals eliminates carrier effects and provides a platform to control the absolute and relative loading of cargo	[34]
		Recombinant protein	Self-assembled proteins can be used to change how an antigen is displayed, thus controlling the desired immune response	[36,42]
		Modified dendrimers	Biomaterials can be used as a tool to efficiently screen vaccine candidates	[50]
	Scaffolds	N-(2-hydroxypropyl)methacrylamide	Density of TLRa on a polymer backbone changes innate immune activation, kinetics, and uptake by APCs	[37]
		Mesoporous silica rods	Porous scaffolds loaded with immune signals recruit and program DCs to home to the LN	[38]
	Microneedles	poly(o-nitrobenzyl-methacrylate-co- methyl-methacrylate-co-poly (ethylene-glycol)-methacrylate)	Microneedles can be used to co-deliver immune signals to the APC rich dermal layer for a simple, pain free vaccine design	[46]
		Poly(L-lactic acid)	Microneedle delivery can improve patient compliance and elicit antigen specific responses	[47]
		Polyvinyl alcohol	Dissolvable microneedle patches are stable and able to produce comparable antibody response to fresh liquid vaccines in humans	[43–45]
	Hybrid biological and biomaterial particle	Poly(β-amino esters)	Hybrid vaccines can be used to engage APC receptors and enhance uptake	[51]
Cancer	Liposomes		Particle encapsulation can be used to target the delivery of chemotherapeutics to decrease systemic effects and safety concerns, increase uptake and processing by APCs, and enhance tumor-specific T cell function. In addition, liposomes can be modified to exploit naturally occurring immune pathways to direct the type of response	[54,63–65, 69,70]
	Polymer Particles	Poly(β-amino esters)	Polymer condensation of DNA cargo can be used to induce the expression of CAR genes in situ eliminating the need for ex vivo expansion	[55]
		Polyanhydride	Different polymer chemistries elicit different levels of response when used to encapsulate model tumor antigen	[52]
		Poly(D,L-lactic-co-glycolic acid)	PLGA NPs co-encapsulating different cargos enhance targeting, uptake, and homing and can change the way a small molecule drug is processed. Polymers can also be used to synthesize artificial APCs to deliver signals in a controlled context. PLGA particles are also being used in conjunction with photothermal therapy to generate tumor associated and deliver the context cues to direct the immune response against them	[53,62,66,72]
		Chitosan	Biomaterials enable formulation of effective vaccines containing whole tumor lysates that actively target DCs where the tumor associated antigens can be processed and presented	[67]
		Poly(lactide-co-glycolide)		[65]
		Synthetic block copolymers	Polymer architecture and pH responsiveness can be optimized for maximum cytosolic delivery of antigen in APCs to maximize activation of the STING pathway	[61]
		Polystyrene	Bispecific nanobioconjugates are useful to induce selective immune-mediated eradication of breast cancer by bringing the appropriate cell types together	[71]
	Microneedles	Hyaluronic acid	Microneedles can be exploited to target the delivery of checkpoint blockade therapies to appropriate cell types, reducing adverse systemic effects	[68]
		Poly(L-lactide)	Co-delivering a tumor antigen and TLRa via microneedles elicits antigen specific T cell expansion in a painless approach	[60]
	Self-assembled particles	Polyethylenimine and DNA	NPs can protect DNA cargo and co-deliver enhancing immune cues in an oral vaccine	[59]
	Scaffolds	Cryogel	Scaffolds can be used to co-deliver signals to increase DC infiltration at the site of infection	[57]
		Alginate	Implantable biopolymers can be used to target delivery of CAR T cells directly to the site of solid tumors. Alginate scaffolds can also deliver immune signals to increase T cell proliferation with memory phenotypes at a resection site	[58,73]
Tolerance	Polymer particles	Poly(D,L-lactic-co-glycolic acid)	Regulatory small molecules and immune signals can be delivered more safely and effectively using particle encapsulation. Particles can be used to co-deliver signals in a controlled release manner to change the immune response against an self-antigen	[75–78,84, 88–90,97,98]
		Polystyrene	Negatively charged MPs are taken up by inflammatory monocytes and sequestered in the spleen decreasing systemic inflammation	[76,77]
		Iron oxide	Artificial APCs can be used to expand self-antigen specific regulatory T cell populations and as tools to probe the key design features	[82,83]
		QDs	Allows for precise control over self-antigen display on surfaces to drive tolerance	[79]
	Self-assembled immune signals	Immune signals	Self-assembled immune signals protect cargo from degradation and reduce antigen specific disease in mouse models of MS	[86,87]
	Scaffolds	Poly(D,L-lactic-co-glycolic acid)	Encapsulation of insulin and immune signals in a scaffold alter the response to the antigen	[91]
		Alginate	Scaffolds can be used to target the delivery of regulatory immune signals and drugs	[94]
		Triglycerol monostearate	Immunosuppressive drug loaded into a hydrogel allows for controllable release in response to proteolytic enzyme overexpressed during inflammation	[95]
		Acellular dermal matrix		[96]
	Engineered erythrocytes		Red blood cells can be exploited for their non-inflammatory clearance to promote tolerance against conjugated antigens	[80,81]