Chitosan Based Biomaterials Volume 2: Tissue Engineering and Therapeutics

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Berthod, F. Bonnassar, L. Boyce, S. Mater: Res. Cao, X.

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The Design of Scaffolds for Use in Tissue Engineering. Part I. Traditional Factors

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Gabrilovich, D. Immunother: Emphasis Tumor Immuno. Gillery, P. Guidry, C. Cell Biol. Gullberg, D. Cell Res. Ho-Sung, L. Huc, A. Imamura, E.


Kahn, A. Khor, E. Klein, C. Kleinmann, H. Klopper, P. Lambert, C. Langer, R. Langholz, O. Levy, R. McCoy, J. McPherson, J. Mauch, C. Middelkoop, E. Miyata, T.

Montesano, R. Moullier, P. Naffakh, N. Nakagawa, S. Nimni, M. Nishiyama, T. Immune system plays a critical role in the health of organisms and can be either a cure or cause of diseases. Strategies to enhance, suppress or qualitatively shape the immune response are of great importance for diverse biomedical applications, such as the development of new vaccines, treatments for autoimmune diseases and allergies, immunotherapies for cancer and strategies for regenerative medicine. Currently, increasing interests are focusing on engineering biomaterials to rationally control the immune system by enhancing or suppressing immune reactions in an antigen-specific or nonspecific manner to treat disease or overcome adverse immune situations.

Among them, new strategies for vaccination using biomaterials are highlighted.

Journal of Biomaterials and Tissue Engineering

Vaccination is an important way of controlling and potentially eliminating infectious diseases and cancers. Traditional live-attenuated vaccines have been used for a long time, but serious safety concerns regarding toxicity and the risk of mutation back to the infectious pathogen have largely limited their application [ 65 , 66 ].

In recent years, subunit vaccines composed of purified or recombinant antigens with ensure safety have gained much attention, but they do not provide sufficient immunostimulation necessary for robust protection [ 67 , 68 ]. Biomaterials-based antigen delivery systems have emerged as an innovative strategy to improve the efficacy of subunit vaccines. The antigen delivery systems are often used to enhance the delivery and presentation of antigens to antigen presenting cells APCs in order to improve the efficacy of the vaccination strategy.

Pioneering work has been done in encapsulating antigens, immunomodulatory agents and immunostimulatory drugs inside antigen delivery systems.

Tissue Engineering: Biology - Scaffolds - Materials Science

Meanwhile, the delivery systems may exert different functions, depending on the specific properties of delivery system. Lipid-based delivery systems like emulsions, virosomes and liposomes have been widely used in vaccines, even some of them like liposomes and ISCOMs are undergoing clinical development [ 73 ].

They are versatile antigen delivery systems since their physicochemical properties can be easily varied by adjusting the lipid composition and the content of additional immunopotentiating components that associated, encapsulated or intercalated in the lipid membrane [ 72 ]. Cationic liposomes based on dimethyldioctadecylammonium and the immunopotentiating glycolipid trehalosedibehenate Adjuvant CAF01 can promote humoral immune responses and cell-mediated immune responses in preclinical animal models and has completed its Phase I clinical trial in combination with HIV-1 peptides for treatment of patients with chronic HIV-infection NCT Another example is ISCOMs, which are lipid particles comprising cholesterol, phospholipids and cell membrane antigens with the immunostimulatory fraction from Quillaja saponaria Quil A incorporated.

ISCOMs have been shown to induce both humoral and cellular immune responses in humans and evaluated in clinical trials [ 72 ]. Additionally, Tecemotide, a therapeutic vaccine consists of a MUC1 lipopeptide combined with monophosphoryl lipid A in a liposomal delivery vehicle, has been designed to induce immune response to cancer cells expressing MUC1. Polymeric micro-and nanoparticles have also been studied widely as vaccine delivery systems due to their ability to mediate cross-presentation [ 76 ].

The most commonly used polymer for vaccination is the biocompatible and biodegradable polymer poly lactic-co-glycolic acid PLGA formulated into either nano- or microparticles. PLGA microparticles encapsulating antigen have been shown to enhance cross-presentation and the induction of CTL responses [ 77 ]. Particularly, combination PLGA particles with immunopotentiating compounds have been validated to be a promising strategy for further improving the vaccine efficacy [ 72 , 78 ]. Polyelectrolyte capsules fabricated by layer-by-layer LBL coating of template nano- or microparticles with oppositely charged polyelectrolytes have also been applied to encapsulated protein or peptide antigens [ 79 ].

Polymeric scaffolds and hydrogels with 3D polymeric networks have been widely used for cell encapsulation and controlled release of therapeutic proteins, peptides, drugs and nucleic acids due to their biocompatibility, design flexibility and a broad spectrum of choice of base material [ 70 ]. Choice of materials for forming scaffolds and hydrogels ranged from natural polymers dextran, alginate, gelatin, hyaluronic acid etc. On one hand, 3D scaffolds or hydrogels can be used as immunological microenvironments and delivery of ex vivo programmed immune cells, such as dendritic cells DCs and adoptive T cells, attributed to their macroporous properties.

On the other hand, they can also been used to simultaneously encapsulate antigen and adjuvant and provide a depot to controlled release the loading cargos, which could induce and program immune cells in situ. In the preclinical study, these scaffolds recruited naive DCs and programmed them to induce robust prophylactic immunity against murine B16F10 melanoma tumor. Subsequently, CpG oligonucleotides complexed to cationic polymer PEI loaded into the scaffolds activated the DC in the implant in situ [ 81 ].

More importantly, the group of David Mooney also investigated the ability of these scaffolds to provide therapeutic vaccination against established melanoma.

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The researchers combined this vaccine with antibodies that block either the protein cytotoxic T lymphocyte antigen4 or a protein called programed death 1, two immune checkpoint receptors. They found a single dose of the vaccine alone inhibited cancer growth in mice with established melanoma. Stem-cell-based therapies have existed since the first successful bone marrow transplantations in [ 82 , 83 ]. In the subsequent development, significant progress has been made in the field of cardiovascular disease, tissue engineering cartilage, bone, spinal injury etc. For instances, transplantation of stem cells into the heart can improve cardiac function after myocardial infarction and in chronic heart failure [ 84 ].

Mesenchymal stem-cell therapy is capable to rebuild cartilage [ 85 ].

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However, survival of transplanted stem cells into diseased tissues or organs is poor, and new strategies are needed to enhance stem cell differentiation and survival in vivo. In recent years, progress in biomaterials design and engineering enabled a new generation of instructive materials to emerge as good candidates for stem-cell-based therapies [ 86 ].

On one hand, biomaterials, which mimic naturally occurring extracellular matrix ECM could instruct stem cell function in different ways. On the other hand, biomaterials could also able to promote angiogenesis, enhance engraftment and differentiation of stem cells, and accelerate electromechanical integration of transplanted stem cells.