TY - JOUR
T1 - Eluted 25-hydroxyvitamin D3 from radially aligned nanofiber scaffolds enhances cathelicidin production while reducing inflammatory response in human immune system-engrafted mice
AU - Chen, Shixuan
AU - Ge, Liangpeng
AU - Wang, Hongjun
AU - Cheng, Yan
AU - Gorantla, Santhi
AU - Poluektova, Larisa Y.
AU - Gombart, Adrian F.
AU - Xie, Jingwei
N1 - Funding Information:
This work was supported partially from startup funds from the University of Nebraska Medical Center (UNMC) and National Institute of General Medical Science (NIGMS) of the National Institutes of Health under Award Numbers R01GM123081 and 1U54GM115458. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
This work was supported partially from startup funds from the University of Nebraska Medical Center (UNMC) and National Institute of General Medical Science (NIGMS) of the National Institutes of Health under Award Numbers R01GM123081 and 1U54GM115458 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2019 Acta Materialia Inc.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Vitamin D3 modulates immune response, induces endogenous antimicrobial peptide production, and enhances innate immunity to defend against infections. These findings suggest that incorporating vitamin D3 into medical devices or scaffolds could positively modulate host immune response and prevent infections. In the current study, we evaluated host responses and endogenous antimicrobial peptide production using 25-hydroxyvitamin D3 (25(OH)D3)-eluting radially aligned PCL nanofiber scaffolds in human immune system-engrafted mice. We transformed traditional 2D electrospun nanofiber membranes into radially aligned PCL nanofiber scaffolds using the concept of solid of revolution and an innovative gas-foaming technique. Such scaffolds can promote rapid cellular infiltration and neovascularization. The infiltrating immune cells within subcutaneously implanted 25(OH)D3-containing scaffolds mainly consisted of human macrophages in the M1 phase (CCR7+), mice macrophages in the M2 phase (CD206+), and human cytotoxic T cells (CD8+) other than few human T-helper cells (CD4+). The 25(OH)D3-eluting nanofiber scaffolds significantly inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6), while accelerating the production of anti-inflammatory cytokines (IL-4, IL-10) within the scaffolds. Additionally, we observed increased expression of human cathelicidin LL-37 within the 25(OH)D3-eluting scaffolds, while no LL-37 expression was observed in the control. Together, these findings support further work in the design of vitamin D3-eluting medical devices or scaffolds for modulating immune response and promoting antimicrobial peptide production. This could potentially reduce the inflammatory response, prevent infections, and eventually improve success rates of implants. Statement of Significance: Transplant failure of medical devices, grafts, scaffolds, and tissue-engineered constructs due to inflammation and infection causes not only economic losses but also sufferings of second operation to the patient. Positive modulation of the host response to implants, scaffolds, and tissue-engineered constructs is likely to reduce the failure rate. Vitamin D3 plays an important role in modulating the immune response. It is able to not only reduce inflammation and induce endogenous antimicrobial peptide production but also prevent multidrug resistance and other side effects of traditional antibiotics. In this study, host responses to 25-hydroxyvitamin D3 (25(OH)D3)-eluting radially aligned PCL nanofiber scaffolds were evaluated in human immune system-engrafted mice. The 25(OH)D3-eluting medical devices or scaffolds were able to modulate positive immune response and promote antimicrobial peptide production. This work presented an innate immunity-enhancing approach for reducing the inflammatory response and preventing infections, likely resulting in improvement of success rates of implants.
AB - Vitamin D3 modulates immune response, induces endogenous antimicrobial peptide production, and enhances innate immunity to defend against infections. These findings suggest that incorporating vitamin D3 into medical devices or scaffolds could positively modulate host immune response and prevent infections. In the current study, we evaluated host responses and endogenous antimicrobial peptide production using 25-hydroxyvitamin D3 (25(OH)D3)-eluting radially aligned PCL nanofiber scaffolds in human immune system-engrafted mice. We transformed traditional 2D electrospun nanofiber membranes into radially aligned PCL nanofiber scaffolds using the concept of solid of revolution and an innovative gas-foaming technique. Such scaffolds can promote rapid cellular infiltration and neovascularization. The infiltrating immune cells within subcutaneously implanted 25(OH)D3-containing scaffolds mainly consisted of human macrophages in the M1 phase (CCR7+), mice macrophages in the M2 phase (CD206+), and human cytotoxic T cells (CD8+) other than few human T-helper cells (CD4+). The 25(OH)D3-eluting nanofiber scaffolds significantly inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6), while accelerating the production of anti-inflammatory cytokines (IL-4, IL-10) within the scaffolds. Additionally, we observed increased expression of human cathelicidin LL-37 within the 25(OH)D3-eluting scaffolds, while no LL-37 expression was observed in the control. Together, these findings support further work in the design of vitamin D3-eluting medical devices or scaffolds for modulating immune response and promoting antimicrobial peptide production. This could potentially reduce the inflammatory response, prevent infections, and eventually improve success rates of implants. Statement of Significance: Transplant failure of medical devices, grafts, scaffolds, and tissue-engineered constructs due to inflammation and infection causes not only economic losses but also sufferings of second operation to the patient. Positive modulation of the host response to implants, scaffolds, and tissue-engineered constructs is likely to reduce the failure rate. Vitamin D3 plays an important role in modulating the immune response. It is able to not only reduce inflammation and induce endogenous antimicrobial peptide production but also prevent multidrug resistance and other side effects of traditional antibiotics. In this study, host responses to 25-hydroxyvitamin D3 (25(OH)D3)-eluting radially aligned PCL nanofiber scaffolds were evaluated in human immune system-engrafted mice. The 25(OH)D3-eluting medical devices or scaffolds were able to modulate positive immune response and promote antimicrobial peptide production. This work presented an innate immunity-enhancing approach for reducing the inflammatory response and preventing infections, likely resulting in improvement of success rates of implants.
KW - 25-Hydroxyvitamin D
KW - Cathelicidin production
KW - Inflammatory response
KW - Radially aligned nanofiber scaffolds
KW - Sustained release
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U2 - 10.1016/j.actbio.2019.08.005
DO - 10.1016/j.actbio.2019.08.005
M3 - Article
C2 - 31386930
AN - SCOPUS:85070303881
SN - 1742-7061
VL - 97
SP - 187
EP - 199
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -