Role of Dendritic Cells in Response to Biomaterials

Lewis, Jamal S.; Keselowsky, Benjamin G.

doi:10.1016/b978-0-12-800196-7.00007-4

Cited by 2 publications

(1 citation statement)

References 95 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When biomaterial vehicles are engineered to deliver immunomodulators, it is important that the biomaterial itself does not elicit a response from the DCs. Advancements in the area of host response to biomaterials, either singularly or as part of combination devices, including biologics, show that DCs are critical to the success of these materials in vivo . − DCs respond to a variety of biomaterials by undergoing changes in their expressed phenotypes. − For instance, in vitro , agarose-treated human , or murine DCs maintain a relatively quiescent state compared to stimulatory positive controls. Contact of immature DCs with agarose maintains them in an immature phenotype and induces autologous regulatory T-cells in cocultures.…”

Section: Introductionmentioning

confidence: 99%

Controlled Delivery of Immunomodulators from a Biomaterial Scaffold Niche to Induce a Tolerogenic Phenotype in Human Dendritic Cells

Srinivasan

Babensee

2020

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

Engineering a regulatory phenotype in dendritic cells (DCs) is a potential approach to circumvent an immune response against self-antigens in autoimmunity or alloantigens in allograft rejection. Cell microenvironments influence the differentiation of DC precursors into either proinflammatory/ immunostimulatory or tolerogenic/regulatory DCs. Biomaterial-based vehicles can be used to re-engineer cell microenvironments and re-educate the DC phenotype. This study presents the development and validation of a biomaterial-based multicomponent immunomodulatory (MI) scaffold for the purpose of promoting a tolerogenic/regulatory DC phenotype. Glutaraldehyde-crosslinked gelatin microparticles, loaded with specific immunomodulators, were embedded into a porous agarose scaffold. Using the Weibull equation and the Bayesian approach, an empirical mathematical model was derived from the release profile data of "model" molecules. The scaffold design was generated from the model to achieve distinct temporal release profiles of the loaded immunomodulator(s): granulocyte monocyte colony-stimulating factor (GM-CSF), dexamethasone (DEX), and/or peptidoglycan (PGN). The MI scaffold-treated DCs (MI DCs) showed an increase in the expression of tolerogenic markers such as surface immunoglobulin-like transcript 3 (ILT-3) and secreted interleukin-10 (IL-10), with a simultaneous decrease in maturation markers such as CD86 and secreted interferon-γ (IFN-γ). In cell culture studies, these MI DCs were able to suppress Tcell proliferation. This approach is expected to enhance the generation of endogenous regulatory DCs when applied in vivo. This technology serves as a basis for future immunotherapeutic applications in the autoimmunity and allogeneic therapies. It also shows that empirical mathematical modeling can be used to engineer scaffold designs for distinct temporal release of one or more immunomodulators.

show abstract

Section: Introductionmentioning

confidence: 99%

Controlled Delivery of Immunomodulators from a Biomaterial Scaffold Niche to Induce a Tolerogenic Phenotype in Human Dendritic Cells

Srinivasan

Babensee

2020

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

show abstract

The role of dendritic cells in the immunomodulation to implanted biomaterials

et al. 2022

View full text Add to dashboard Cite

Considering the substantial role played by dendritic cells (DCs) in the immune system to bridge innate and adaptive immunity, studies on DC-mediated immunity toward biomaterials principally center on their adjuvant effects in facilitating the adaptive immunity of codelivered antigens. However, the effect of the intrinsic properties of biomaterials on dendritic cells has not been clarified. Recently, researchers have begun to investigate and found that biomaterials that are nonadjuvant could also regulate the immune function of DCs and thus affect subsequent tissue regeneration. In the case of proteins adsorbed onto biomaterial surfaces, their intrinsic properties can direct their orientation and conformation, forming “biomaterial-associated molecular patterns (BAMPs)”. Thus, in this review, we focused on the intrinsic physiochemical properties of biomaterials in the absence of antigens that affect DC immune function and summarized the underlying signaling pathways. Moreover, we preliminarily clarified the specific composition of BAMPs and the interplay between some key molecules and DCs, such as heat shock proteins (HSPs) and high mobility group box 1 (HMGB1). This review provides a new direction for future biomaterial design, through which modulation of host immune responses is applicable to tissue engineering and immunotherapy.

show abstract

Role of Dendritic Cells in Response to Biomaterials

Cited by 2 publications

References 95 publications

Controlled Delivery of Immunomodulators from a Biomaterial Scaffold Niche to Induce a Tolerogenic Phenotype in Human Dendritic Cells

Controlled Delivery of Immunomodulators from a Biomaterial Scaffold Niche to Induce a Tolerogenic Phenotype in Human Dendritic Cells

The role of dendritic cells in the immunomodulation to implanted biomaterials

Contact Info

Product

Resources

About