免疫系统工程水凝胶《Advanced NanoBiomed Research》
Hydrogels for Engineering the Immune System
Hydrogels for Engineering the Immune System
Xianlei Li, Yufeng Shou, Andy Tay
Department of Biomedical Engineering, National University of Singapore, 117583 Singapore
Institute for Health Innovation and Technology, National University of Singapore, 117599 Singapore
Advanced NanoBiomed Research, Volume1, Issue3
March 2021, 2000073
First published: 17 January 2021
https://doi.org/10.1002/anbr.202000073
Review
Abstract
Human immune system has evolved as one of the most powerful defense systems to protect against invading pathogens and mutated cells. However, when persistent immune suppression or activation occurs, it can lead to adverse, chronic physiological effects including cancer and arthritis. Hydrogels are soft materials that can be engineered to modulate immune responses through controlled biomolecule release/adsorption, regeneration of lymphoid tissues, and enhanced antigen presentations. This is achieved by programming hydrogels to exhibit optimal properties such as porosity, biodegradability, and biocompatibility to interface seamlessly with the immune system. Herein, recent innovations and future challenges are described using programmable hydrogels to regenerate the lymphatic system, modulate inflammation, and enhance cancer immunotherapy. Key properties of hydrogels are also highlighted for engineering the immune system and techniques to characterize these properties.
Figure 1. Hydrogels for regenerating the lymphatic system.
水凝胶用于再生淋巴系统。
Figure 2. Hydrogels served as “molecular scavenger” to modulate inflammation.
水凝胶作为“分子清除剂”调节炎症。
Figure 3. Hydrogels served as drug/biomolecule reservoirs to ameliorate inflammatory response.
水凝胶用作药物/生物分子库以改善炎症反应。
Figure 4. Hydrogels substantially contributed for high-efficiency antigen uptake and presentation.
水凝胶大大有助于高效抗原的摄取和呈现。
Figure 5. Hydrogels strikingly ameliorated ICB therapeutic toxicity and reversed immunosuppressive TME.
水凝胶显著改善了ICB治疗毒性并逆转了免疫抑制性TME。
Table 1. Key properties and rationale of hydrogels used for engineering immune system
用于免疫系统工程水凝胶的关键特性和原理
| Purposesa) | Materials used | Key properties optimized and rationale |
|---|---|---|
| Regenerate lymphatic system | Gelatin[40] Alginate[45] Collagen[48] Peptide[51] HPMC[53] PEG[59] | 3D structure, mechanical properties such as stiffness and aqueous resembling native tissues and ECM matrices Network structure for high drug loading capability ECM-like matrices and aqueous content for implanted cells viability Porous/biodegrade property for sustained drug release Continuous pore-channels allows intercellular junction as conducive to the formation of tissue Biocompatibility/biodegradability to prevent adverse immune reactions |
| Modulate inflammation | StarPEG[62] Hydroexythylcellulose[63] Polyacrylamide[66] Peptide[79] HA[26] Alginate[97] | Naturally occurring polymers like hyaluronic acids with inherent anti-inflammatory bioactivity Controlled porosity for inflammatory molecule absorption Optimal porosity and tunable biodegradability for controlled drug release ECM-like feature to improve wound healing Trigger responsive for on-demand drug release |
| Improve cancer immunotherapy | PCL-PEG-PCL[100] Piptide[110] Alginate[118] Fibrin[114] Poloxamer 407[128] Polyvinyl alcohol[119] Betamethasone phosphate[134] Supramolecular prodrug[135] | Phase-transition and in situ gel formation (induced by temperature, shear stress, light, ions, etc.) for good injectability Network structures make hydrogels as reservoir to physical encapsulate or chemically link some drug molecules. Tunable porous structure allows drug/cells release and entrance Local delivery drug to relieve systemic toxicity High water content for prolonged activity of bio-drugs or co-trapped cells Aqueous content satisfies the condition of chemical reaction, such as in situ labeling immune cells via click chemistry. Inherent physicochemical properties of materials to reverse immunosuppressive tumor microenvironment |
a) Abbreviation: HPMC = hydroxypropyl methylcellulose; PEG = Polyethylene glycol; HA = hyaluronic acid; PCL-PEG-PCL = poly-(caprolactone)-poly(ethylene glycol)-poly(caprolactone); 3D = three dimensional; ECM = extracellular matrix; VEGF-C = Vascular endothelial growth factors C.