Designing biomaterials with immunomodulatory properties for tissue engineering and regenerative medicine

Andorko, James I.; Jewell, Christopher M.

doi:10.1002/btm2.10063

Cited by 161 publications

(130 citation statements)

References 140 publications

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“…More importantly, activated DCs were only observed in 20 μm pore scaffolds on Day 7. As the immune response is shaped collectively by the various cell types at the implantation site (Andorko & Jewell, ), it is possible that the interplay between DCs and other host cell types at the implant site intensified the adjuvant effect of the porous scaffold in vivo.…”

Section: Discussionmentioning

confidence: 99%

Precision‐porous templated scaffolds of varying pore size drive dendritic cell activation

Chen

Zhang

et al. 2018

Biotech & Bioengineering

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Scaffold based systems have shown significant potential in modulating immune responses in vivo. While there has been much attention on macrophage interactions with tissue engineered scaffolds for tissue regeneration, fewer studies have looked at the effects of scaffold design on the response of immune cells−that is, dendritic cells (DCs). Here, we present the effects of varying pore size of poly (2-hydroxyethyl methacrylate) (pHEMA) and poly(dimethylsiloxane) (PDMS, silicone) scaffolds on the maturation and in vivo enrichment of DCs. We employ a precision templating method to make 3-D porous polymer scaffolds with uniformly defined and adjustable architecture. Hydrophilic pHEMA and hydrophobic PDMS scaffolds were fabricated in three pore sizes (20, 40, 90 μm) to quantify scaffold pore size effects on DCs activation/maturation in vitro and in vivo. In vitro results showed that both pHEMA and PDMS scaffolds could promote maturation in the DC cell line, JAWSII, that resembled lipopolysaccharide (LPS)-activated/matured DCs (mDCs). Scaffolds with smaller pore sizes correlate with higher DC maturation, regardless of the polymer used. In vivo, when implanted subcutaneously in C57BL/6J mice, scaffolds with smaller pore sizes also demonstrated more DCs recruitment and more sustained activation. Without the use of DC chemo-attractants or chemical adjuvants, our results suggested that DC maturation and scaffold infiltration profile can be modulated by simply altering the pore size of the scaffolds.

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Section: Discussionmentioning

confidence: 99%

Precision‐porous templated scaffolds of varying pore size drive dendritic cell activation

Chen

Zhang

et al. 2018

Biotech & Bioengineering

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“…Biomaterials derived from mammalian extracellular matrix (ECM) have been widely used in surgical wound repair, tissue reconstruction and tissue engineering due to their good biocompatibility [1,2]. However, the immune risk caused by animal derived biomaterials or xenogeneic organs directly affected the safety and effectiveness of these materials and limited their applications [1,3,4]. Immune reactions between the antigen on xenografts and the antibody in humans may lead to immune mediated tissue degeneration and dystrophic calcification [5].…”

Section: Introductionmentioning

confidence: 99%

Xenogeneic bone matrix immune risk assessment using GGTA1 knockout mice

Shao

Ling

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Homeotransplantation of bones for replacement therapy have been demonstrated reliably in clinical data. However, human donor bones applicable for homeotransplantation are in short supply, which facilitates the search for suitable alternatives, such as xenografts grafts. The α-Gal antigen-related immune risk of xenografts directly affects the safety and effectiveness of the biomaterials and limits their applications in the clinic. The immune risk can be prevented by depletion or breaking anti-Gal antibody prior to transplant. Therefore, how to assess the immune risk of the bone substitutes and select the reliable animal research model become extremely important. In this study, we prepared lyophilized bone substitutes (T1) and Guanghao Biotech bone substitutes (T2, animal-derived biomaterials with α-Gal antigen decreased), aimed to assess the immune risk of xenografts bone substitutes on GGTA1 knockout mice. The α-Gal antigen contents of T1 and T2 were firstly detected by ELISA method in vitro. The bone substitutes were then implanted subcutaneously into GGTA1 knockout mice for 2, 4 and 12 weeks, respectively. The total serum antibody levels, anti-α-Gal antibody levels, inflammatory cytokine and splenic lymphocyte surface molecules were detected and histology analysis of skin and thymus were performed to systematically evaluate the immune response caused by the T1 and T2 bone substitutes in mice. In vitro results showed that the amount of α-Gal epitopes in T1 bone substitutes was significantly higher than T2 bone substitutes, and the clearance rate of α-Gal antigen in T2 bone substitutes achieved about 55.6%. Results of antibody level in vivo showed that the T1 bone substitutes group possessed significantly higher total IgG, IgM, IgA and anti-α-Gal IgG levels than T2 and control group, while T2 group showed no significant changes of these indexes compared with control. In terms of inflammatory cytokines, T1 bone substitutes showed evidently higher levels of IL-4, IL-12P70 and IL-10 than T2 and control, while T2 group was comparable to control. No changes in the levels of splenic lymphocyte surface molecules were found in the three groups (T1, T2 and control group) during the experimental periods. The pathological results demonstrated that the inflammatory response in T2 group was lighter than the T1 group, which was in accordance with the inflammatory cytokines levels. The above results indicated that the process of antigen removal effectively reduced the α-Gal antigens content in T2 bone substitutes, which caused little immune response in vivo and could be used as bone healing materials. This study also demonstrated that GGTA1 knockout mice can be used as a routine tool to assess the immune risk of animal-derived biomaterials.

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“…To optimize the response of bone biomaterials and avoid excessive inflammation or implant rejection, different immunomodulation approaches have been adopted to interfere with the immune system [24][25][26][27][28][29][30].…”

Section: Of 19mentioning

confidence: 99%

Macrophage in vitro Response on Hybrid Coatings Obtained by Matrix Assisted Pulsed Laser Evaporation

et al. 2019

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The improvement in the research area of the implant by surface functionalization when correlated with the biological response is of major interest in the biomedical field. Based on the fact that the inflammatory response is directly involved in the ultimate response of the implant within the body, it is essential to study the macrophage-material interactions. Within this context, we have investigated the composite material-macrophage cell interactions and the inflammatory response to these composites with amorphous hydroxyapatite (HA), Lactoferrin (Lf), and polyethylene glycol-polycaprolactone (PEG-PCL) copolymer. All materials are obtained by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique and characterized by Atomic Force Microscopy and Scanning Electron Microscopy. Macrophage-differentiated THP-1 cells proliferation and metabolic activity were assessed by qualitative and quantitative methods. The secretion of tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) cytokine, in the presence and absence of the inflammatory stimuli (bacterial endotoxin; lipopolysaccharide (LPS)), was measured using an ELISA assay. Our results revealed that the cellular response depended on the physical-chemical characteristics of the coatings. Copolymer-HA-Lf coatings led to low level of pro-inflammatory TNF-α, the increased level of anti-inflammatory IL-10, and the polarization of THP-1 cells towards an M2 pro-reparative phenotype in the presence of LPS. These findings could have important potential for the development of composite coatings in implant applications.

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Designing biomaterials with immunomodulatory properties for tissue engineering and regenerative medicine

Cited by 161 publications

References 140 publications

Precision‐porous templated scaffolds of varying pore size drive dendritic cell activation

Precision‐porous templated scaffolds of varying pore size drive dendritic cell activation

Xenogeneic bone matrix immune risk assessment using GGTA1 knockout mice

Macrophage in vitro Response on Hybrid Coatings Obtained by Matrix Assisted Pulsed Laser Evaporation

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