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Intro -- Immunomodulatory Biomaterials: Regulating the Immune Response with Biomaterials to Affect Clinical Outcome -- Copyright -- Contents -- Contributors -- Preface -- Chapter 1: Engineering physical biomaterial properties to manipulate macrophage phenotype: From bench to bedside -- 1.1. Introduction -- 1.2. Role of macrophages in tissue repair and the foreign body response -- 1.3. Modulation of macrophage function via physical biomaterial properties in vitro -- 1.3.1. Stiffness -- 1.3.2. Topography or 3D architecture -- 1.3.3. Ligand presentation or geometry of adhesion -- 1.4. Macrophage response to implanted biomaterials in vivo -- 1.4.1. Non-degradable biomaterials -- 1.4.2. Degradable biomaterials -- 1.5. Clinical insight into the effect of physical biomaterial properties on macrophages during tissue repair -- 1.5.1. Dental implants -- 1.5.2. Wound dressings -- 1.5.3. Materials for cardiovascular repair -- 1.6. Conclusions and future directions -- References -- Chapter 2: Early factors in the immune response to biomaterials -- 2.1. Introduction -- 2.2. Protein adsorption -- 2.2.1. Complement cascade -- 2.2.2. Coagulation -- 2.2.3. Immunoglobulins -- 2.2.4. Innate immunity -- 2.2.4.1. Neutrophils -- 2.2.4.2. Mast cells -- 2.2.4.3. Macrophages/monocytes -- 2.2.5. Adaptive immunity -- 2.2.5.1. Dendritic cells -- 2.2.5.2. T Cells -- 2.2.5.3. B Cells -- 2.3. Foreign body giant cells -- 2.4. Fibrous capsule -- 2.5. Signaling pathways activated -- 2.5.1. TLRs and MyD88-dependent signaling -- 2.5.2. Inflammasome activation -- 2.5.3. JAK/STAT pathway -- 2.6. Conclusion -- References -- Chapter 3: Nanotechnology and biomaterials for immune modulation and monitoring -- 3.1. Introduction -- 3.2. Autoimmunity -- 3.3. Allergy -- 3.4. Transplant rejection -- 3.5. Clinical trials of tolerogenic nanotherapies -- 3.5.1. Liposomal.

3.5.2. Virus-like particles -- 3.5.3. Metallic -- 3.5.4. Polymeric -- 3.6. Precision diagnostics -- 3.6.1. Liquid biopsy -- 3.6.2. Immunological niches -- 3.7. Outlook and conclusion -- Acknowledgments -- References -- Chapter 4: Immune-instructive materials and surfaces for medical applications -- 4.1. Introduction -- 4.1.1. Immune cells involved in inflammation -- 4.1.2. The foreign body response -- 4.2. Naturally occurring biomaterials with immune modulatory properties and their application in wound healing and reduct ... -- 4.3. Bioinstructive synthetic materials and their application in regenerative medicine -- 4.4. Developing ``immune-instructive�� biomaterials -- 4.5. Concluding remarks -- References -- Chapter 5: Electrospun tissue regeneration biomaterials for immunomodulation -- 5.1. Introduction -- 5.2. Acknowledging immunomodulation in tissue engineering -- 5.3. Well-studied areas -- 5.3.1. Monocytes and macrophages -- 5.3.2. Platelets -- 5.4. Areas gaining attention -- 5.4.1. Neutrophils -- 5.4.2. Mast cells -- 5.5. Areas needing attention -- 5.5.1. Dendritic cells -- 5.5.2. Eosinophils -- 5.5.3. Basophils -- 5.5.4. Natural killer cells -- 5.5.5. T cells -- 5.5.6. B cells -- 5.6. Future directions -- 5.7. Conclusion -- References -- Chapter 6: Biomaterials and immunomodulation for spinal cord repair -- 6.1. Spinal cord injury -- 6.1.1. Acute phase of SCI -- 6.1.2. Subacute phase of SCI -- 6.1.3. Chronic phase of SCI -- 6.1.4. Self-repair after SCI -- 6.1.5. Translational potential of animal models of SCI -- 6.2. Immune response after SCI -- 6.3. Immunomodulation after spinal cord injury -- 6.4. Biomaterials for spinal cord repair -- 6.5. Immunomodulatory biomaterials for spinal cord injury -- 6.5.1. Immunomodulation by surface chemistry -- 6.5.2. Immunomodulation by topography -- 6.5.3. Immunomodulation by delivering agents.

6.5.3.1. Immunomodulation by providing biological ligands -- 6.5.3.2. Immunomodulation by delivering drugs -- 6.5.3.3. Immunomodulation by carrying cells -- 6.6. Natural immunomodulatory materials for spinal cord injury -- 6.7. Considerations and future directions -- 6.8. Conclusions and summary -- Acknowledgments -- References -- Chapter 7: Biomaterial strategies to treat autoimmunity and unwanted immune responses to drugs and transplanted tissu -- 7.1. Introduction -- 7.1.1. Burden of disease -- 7.1.2. Current treatment options and challenges -- 7.1.3. Immunological causes of aberrant immune responses -- 7.1.3.1. Immunological basis for autoimmune diseases -- 7.1.3.2. Immunological basis for transplant rejection, anti-drug antibodies, and allergies -- 7.1.4. Antigen-specific tolerance as a treatment goal -- 7.2. Scope -- 7.3. Biomaterials in development for autoimmunity and anti-drug antibodies -- 7.3.1. Lessons from trials of free peptide and free protein -- 7.3.1.1. Type 1 diabetes -- 7.3.1.2. Multiple sclerosis -- 7.3.2. Antigen delivery vehicles without additional regulatory cues -- 7.3.2.1. Antigen depots -- 7.3.2.2. Nanoparticles -- 7.3.2.3. Alternative nanoparticle vehicles -- 7.3.2.4. Targeting liver APCs -- 7.3.2.5. Targeting splenic APCs -- 7.3.3. Antigen delivery vehicles with additional regulatory cues -- 7.3.3.1. Small molecule immunomodulators -- 7.3.3.2. Cytokines -- 7.3.4. Peptide-MHC complexes -- 7.3.4.1. Soluble pMHC complexes -- 7.3.4.2. Multimeric pMHC complexes -- 7.3.4.3. Nanoparticle pMHC complexes -- 7.4. Biomaterials in development for transplant tolerance -- 7.4.1. Transplant ECDI-treated cells -- 7.4.2. PLGA scaffold with transplanted cells and additional immunomodulatory drugs -- 7.5. Future of the field -- 7.5.1. Challenges and future directions -- 7.5.1.1. Standardization of immunological goals and readouts.

7.5.1.2. Further improvement in nanoparticle design -- 7.5.1.3. Manufacturability -- 7.5.2. Current or upcoming clinical trials -- References -- Chapter 8: Lipids as regulators of inflammation and tissue regeneration -- 8.1. Introduction -- 8.2. LC-MS based approaches to analyze lipids and their oxidation products -- 8.3. Free PUFA and their oxidation products as signals for immunomodulation and tissue regeneration -- 8.4. Oxidized phospholipids as modulators of the inflammatory response -- 8.5. Phospholipid signatures of EV -- 8.6. Hydrolysis of MBV derived oxygenated lipids and their possible role in inflammation and tissue regeneration -- References -- Chapter 9: Biomaterials modulation of the tumor immune environment for cancer immunotherapy -- 9.1. Introduction -- 9.2. Fundamentals of cancer immunology and immunotherapy -- 9.2.1. Cancer biology: Setting the stage -- 9.2.2. The role of immunity in cancer -- 9.3. Immunomodulatory biomaterials in cancer therapy -- 9.3.1. Cancer immunotherapy -- 9.3.2. Immunomodulatory biomaterials -- 9.3.3. Direct interactions between cancer and the biomaterial immune microenvironment -- 9.3.4. Biomaterial scaffold cancer vaccines -- 9.3.5. Biomaterial scaffolds for cell-based cancer immunotherapy -- 9.3.6. Immune tissue engineering -- 9.4. Summary -- References -- Chapter 10: Circumventing immune rejection and foreign body response to therapeutics of type 1 diabetes -- 10.1. Introduction -- 10.1.1. Type 1 diabetes (T1D) -- 10.1.2. Insulin and other injectable therapeutics -- 10.1.3. Biomaterials/devices -- 10.1.4. CGMs and insulin pumps -- 10.1.5. Cellular therapies -- 10.1.6. Protective immunity -- 10.2. Immune rejection for cells/grafts -- 10.2.1. General concepts for graft implementation -- 10.2.2. Transplant procedures -- 10.2.3. Human donor considerations -- 10.2.4. Alternative cell sources.

10.2.4.1. Xenogeneic grafts -- 10.2.4.2. Allogeneic grafts -- 10.2.4.3. Syngeneic grafts -- 10.2.4.4. Autologous grafts -- 10.3. Biological hurdles to preventing graft rejection -- 10.4. Advances in eliminating rejection of non-encapsulated grafts -- 10.4.1. Edmonton protocol and anti-inflammatory strategies -- 10.4.2. Delivery of antigen/nucleotide-based drugs for rejection suppression -- 10.4.3. Engineering therapeutic cells to modulate immune response -- 10.4.4. Tolerogenic vaccines -- 10.4.5. Artificial antigen-presenting cells for inducing tolerance -- 10.5. Advances in preventing FBR to bulk encapsulation systems -- 10.5.1. Bioresorption vs. lack of biodegradability -- 10.5.2. Non-biodegradable hydrogels/alginate and stable immune isolation -- 10.5.3. Effects of altering physical architecture -- 10.5.3.1. Size and shape -- 10.5.3.2. Surface topography and selective porosity -- 10.5.4. Chemical modification of material devices -- 10.5.4.1. Identification of anti-fibrotic chemistries: Surface vs. bulk modified -- 10.5.4.2. Zwitterionic (and other polymer-based) biocompatibility coatings -- 10.5.5. Long-term controlled release systems for rejection prevention -- 10.6. Pre/clinical observations, and models for translation -- 10.6.1. Choosing the right test animal and transplant site -- 10.6.2. Blood flow and nutrient considerations for graft viability -- 10.7. Future prospects and perceived challenges/difficulties -- 10.7.1. Increasing burdens on healthcare -- 10.7.2. Population expansion and increasing age of the general human populace -- 10.7.3. Increase in emerging diseases -- 10.8. Summary/conclusion -- References -- Chapter 11: Machine learning and mechanistic computational modeling of inflammation as tools for designing immuno -- 11.1. Biomaterials, inflammation, and wound healing.