Neovascularized implantable cell homing encapsulation platform with tunable local immunosuppressant delivery for allogeneic cell transplantation

Paez‐Mayorga, Jesus; Capuani, Simone; Hernandez, Nathanael; Farina, Marco; Chua, Corrine Ying Xuan; Blanchard, Ryan; Sizovs, Antons; Liu, Hsuan-Chen; Fraga, Daniel; Niles, Jean A.; Salazar, Hector F.; Corradetti, Bruna; Sikora, Andrew G.; Kloc, Małgorzata; Li, Xian Chang; Gaber, A. Osama; Nichols, Joan E.; Grattoni, Alessandro

doi:10.1016/j.biomaterials.2020.120232

Cited by 35 publications

(52 citation statements)

References 66 publications

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“…In tissue repair and regeneration, the vascularization has a significant impact on the longevity of transplanted cells and rapid tissue integration. [ 45 ] Vascular endothelial growth factors (VEGFs) play a critical role in angiogenesis and microvasculature formation. QK peptide is a VEGF‐mimicking peptide consisting of 15 amino acids, which can enhance the angiogenesis by activating the VEGF receptors.…”

Section: Resultsmentioning

confidence: 99%

Freeze‐Casting with 3D‐Printed Templates Creates Anisotropic Microchannels and Patterned Macrochannels within Biomimetic Nanofiber Aerogels for Rapid Cellular Infiltration

John

McCarthy

Wang

et al. 2021

Adv Healthcare Materials

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A new approach is described for fabricating 3D poly(ε‐caprolactone) (PCL)/gelatin (1:1) nanofiber aerogels with patterned macrochannels and anisotropic microchannels by freeze‐casting with 3D‐printed sacrificial templates. Single layer or multiple layers of macrochannels are formed through an inverse replica of 3D‐printed templates. Aligned microchannels formed by partially anisotropic freezing act as interconnected pores between templated macrochannels. The resulting macro‐/microchannels within nanofiber aerogels significantly increase preosteoblast infiltration in vitro. The conjugation of vascular endothelial growth factor (VEGF)‐mimicking QK peptide to PCL/gelatin/gelatin methacryloyl (1:0.5:0.5) nanofiber aerogels with patterned macrochannels promotes the formation of a microvascular network of seeded human microvascular endothelial cells. Moreover, nanofiber aerogels with patterned macrochannels and anisotropic microchannels show significantly enhanced cellular infiltration rates and host tissue integration compared to aerogels without macrochannels following subcutaneous implantation in rats. Taken together, this novel class of nanofiber aerogels holds great potential in biomedical applications including tissue repair and regeneration, wound healing, and 3D tissue/disease modeling.

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Section: Resultsmentioning

confidence: 99%

Freeze‐Casting with 3D‐Printed Templates Creates Anisotropic Microchannels and Patterned Macrochannels within Biomimetic Nanofiber Aerogels for Rapid Cellular Infiltration

John

McCarthy

Wang

et al. 2021

Adv Healthcare Materials

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“…The adoptive transfer of tolerogenic cells or stem cells has also induced tolerance and/or localized suppression in preclinical and clinical studies [4][5][6] (Figure 2). Finally, bioengineered approaches comprising biomaterials, cells, or combinations thereof [7][8][9] (Figure 3) may provide clues to unveil the mechanisms behind innovative acceptance-inducing strategies (Table 1, Key Table ). The following sections critically review the impact of different strategies on the recipients' response, while addressing the reported biological mechanisms influencing their efficiency.…”

Section: Strategies To Achieve Allograft Acceptance: Advances From Standard-of-care Approachesmentioning

confidence: 99%

“…Finally, a model of allotransplantation received polyethyleneimine (PEI)-poly lactic-co-glycolic acid (PLGA) nanoparticles functionalized with an allogeneic MHC-mimic, CD47, and immunosuppressants (IS), that triggered peripheral deletion of MHC-alloreactive T cells and promoted Treg expansion. Adapted from references [8,67,71,72,74,[76][77][78]82]. tolerogenic DCs achieved 300 days of IS-free survival after transplantation with MHCmismatched livers.…”

Section: Tolerogenic Cells Tolerogenic Leucocytesmentioning

confidence: 99%

“…Few reports in mice models comprise the use of biomaterial-assisting immunomodulatory cells as localized IS/tolerance towards an allogeneic transplant [8,87]. Intraperitoneal delivery of MSCs primed with proinflammatory cytokines provided 50-day survival of co-encapsulated mice islet allografts, without IS [87].…”

Section: Carriers Of Immunomodulatory Cellsmentioning

confidence: 99%

“…The reservoir had 100-300-μm external openings that allowed host vascularization, achieved through 6-week prevascularization. As a result, although fibrotic tissue covered the implant, the local delivery of CTLA-4Ig locally impaired T cell activation, allowing allogeneic cell survival for 31 days [8]. Additional approaches to implement carriers of immunomodulatory cells may be found in reference [93].…”

Section: Carriers Of Immunomodulatory Cellsmentioning

confidence: 99%

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Engineering Strategies for Allogeneic Solid Tissue Acceptance

Sousa

Mano

Oliveira

2021

Trends in Molecular Medicine

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Systemic immunosuppressants have allowed the transplantation of life-saving organs. However, they cause deleterious effects and long-term graft failure. Strategies promoting allogeneic graft acceptance and the maintenance of immunological competence have been proposed.Cell-based tolerance-inducing strategies that preserve immune competence have already extended human allograft acceptance, although toxic side effects or difficult reproduction of observed effects in humans have counteracted their clinical translation.Localized tolerance/immunosuppression mediated through bioengineered setups comprising immunomodulatory biomaterials and/or tissue engineeringinspired tools already achieved allograft acceptance in murine models and are game changing in the field. Such advances have contributed to unveiling the complex interplay of immune cells and allogeneic transplants.

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Enhanced In Vivo Vascularization of 3D‐Printed Cell Encapsulation Device Using Platelet‐Rich Plasma and Mesenchymal Stem Cells

Paez‐Mayorga

Capuani

Farina

et al. 2020

Adv Healthcare Materials

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The current standard for cell encapsulation platforms is enveloping cells in semipermeable membranes that physically isolate transplanted cells from the host while allowing for oxygen and nutrient diffusion. However, long-term viability and function of encapsulated cells are compromised by insufficient oxygen and nutrient supply to the graft. To address this need, a strategy to achieve enhanced vascularization of a 3D-printed, polymeric cell encapsulation platform using platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) is investigated. The study is conducted in rats and, for clinical translation relevance, in nonhuman primates (NHP). Devices filled with PRP, MSCs, or vehicle hydrogel are subcutaneously implanted in rats and NHP and the amount and maturity of penetrating blood vessels assessed via histopathological analysis. In rats, MSCs drive the strongest angiogenic response at early time points, with the highest vessel density and endothelial nitric oxide synthase (eNOS) expression. In NHP, PRP and MSCs result in similar vessel densities but incorporation of PRP ensues higher levels of eNOS expression. Overall, enrichment with PRP and MSCs yields extensive, mature vascularization of subcutaneous cell encapsulation devices. It is postulated that the individual properties of PRP and MSCs can be leveraged in a synergistic approach for maximal vascularization of cell encapsulation platforms.

show abstract

Neovascularized implantable cell homing encapsulation platform with tunable local immunosuppressant delivery for allogeneic cell transplantation

Cited by 35 publications

References 66 publications

Freeze‐Casting with 3D‐Printed Templates Creates Anisotropic Microchannels and Patterned Macrochannels within Biomimetic Nanofiber Aerogels for Rapid Cellular Infiltration

Freeze‐Casting with 3D‐Printed Templates Creates Anisotropic Microchannels and Patterned Macrochannels within Biomimetic Nanofiber Aerogels for Rapid Cellular Infiltration

Engineering Strategies for Allogeneic Solid Tissue Acceptance

Enhanced In Vivo Vascularization of 3D‐Printed Cell Encapsulation Device Using Platelet‐Rich Plasma and Mesenchymal Stem Cells

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