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Shear-thinning hydrogel for allograft cell transplantation and externally controlled transgene expression.
Bezold, Mariah G; Dollinger, Bryan R; DeJulius, Carlisle R; Keech, Megan C; Hanna, Andrew R; Kittel, Anna R; Yu, Fang; Gupta, Mukesh K; D'Arcy, Richard; Brunger, Jonathan M; Duvall, Craig L.
Afiliación
  • Bezold MG; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
  • Dollinger BR; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
  • DeJulius CR; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
  • Keech MC; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
  • Hanna AR; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
  • Kittel AR; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
  • Yu F; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
  • Gupta MK; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
  • D'Arcy R; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
  • Brunger JM; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
  • Duvall CL; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA. Electronic address: craig.duvall@vanderbilt.edu.
Biomaterials ; 314: 122812, 2024 Sep 04.
Article en En | MEDLINE | ID: mdl-39288619
ABSTRACT
This work establishes the design of a fully synthetic, shear-thinning hydrogel platform that is injectable and can isolate engineered, allogeneic cell therapies from the host. We utilized RAFT to generate a library of linear random copolymers of N,N-dimethylacrylamide (DMA) and 2-vinyl-4,4-dimethyl azlactone (VDMA) with variable mol% VDMA and degree of polymerization. Poly(DMA-co-VDMA) copolymers were subsequently modified with either adamantane (Ad) or ß-cyclodextrin (Cd) through amine-reactive VDMA to prepare hydrogel precursor macromers containing complementary guest-host pairing pendant groups that, when mixed, form shear-thinning hydrogels. Rheometric evaluation of the hydrogel library enabled identification of lead macromer structures comprising 15 mol% pendants (Ad or Cd) and a degree of polymerization of 1000; mixing of these Ad and Cd functionalized precursors yielded hydrogels possessing storage modulus above 1000 Pa, tan(δ) values below 1 and high yield strain, which are target characteristics of robust but injectable shear-thinning gels. This modular system proved amenable to nanoparticle integration with surface-modified nanoparticles displaying Ad. The addition of the Ad-functionalized nanoparticles simultaneously improved mechanical properties of the hydrogels and enabled extended hydrogel retention of a model small molecule in vivo. In studies benchmarking against alginate, a material traditionally used for cell encapsulation, the lead hydrogel showed significantly less fibrous encapsulation in a subcutaneous implant site. Finally, this platform was utilized to encapsulate and extend in vivo longevity of inducible transgene-engineered mesenchymal stem cells in an allogeneic transplant model. The hydrogels remained intact and blocked infiltration by host cells, consequently extending the longevity of grafted cell function relative to a benchmark, shear-thinning hyaluronic acid-based gel. In sum, the new synthetic, shear-thinning hydrogel system presented here shows potential for further development as an injectable platform for delivery and in situ drug modulation of allograft and engineered cell therapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomaterials Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomaterials Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos