Development and in vivo evaluation of an implantable nano-enabled multipolymeric scaffold for the management of AIDS dementia complex (ADC)

Harilall, Sheri-lee; Choonara, Yahya E.; Tomar, Lomas K.; Tyagi, Charu; Kumar, Pradeep; Toit, Lisa C. du; Modi, Girish; Naidoo, Dinesh; Iyuke, Sunny E.; Danckwerts, Michael P.; Pillay, Viness

doi:10.1016/j.ijpharm.2015.10.025

Cited by 5 publications

(4 citation statements)

References 37 publications

(52 reference statements)

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“…Many of these investigations have transitioned from in vitro to in vivo in the tissue-engineering field of organs such as retina [46], skin [47], liver [48], digestive tract [49], ear [50], pancreas [51], lungs [52] and skeletal muscle [53]. However the systematic development of a bioengineered scaffold for the brain with DOE studies has been rarely pursued past the in vitro stage [21, 22]. This work provides the first evidence supporting the multi-factorial cell/hydrogel/DOE approach that combines mechanical, biochemical and trophic factors to 1) systematically modify multiple factors at the same time, 2) identify the specific combination that promotes the desired cell behavior and 3) selectively control the in vivo distinct cell fate of transplanted cells.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanical properties of this gel are similar to those of normal brain. HA has been shown to promote angiognesis in a mouse model of skin wound healing [21, 22]. Biotin was then introduced to HA-AC using sulfo-NHS–LC–biotin (NHS–biotin).…”

Section: Methodsmentioning

confidence: 99%

“…Biotin was then introduced to HA-AC using sulfo-NHS–LC–biotin (NHS–biotin). NHS–biotin (100mg) was added as a solid to a solution of HA–AC (300 mg; 3 mg/mL in PBS; pH 7.4) as previously described [22]. The reaction proceeded for 16 hours at room temperature with stirring.…”

Section: Methodsmentioning

confidence: 99%

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Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain

et al. 2016

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Stem cell therapies have shown promise in promoting recovery in stroke but have been limited by poor cell survival and differentiation. We have developed a hyaluronic acid (HA)-based self-polymerizing hydrogel that serves as a platform for adhesion of structural motifs and a depot release for growth factors to promote transplant stem cell survival and differentiation. We took an iterative approach in optimizing the complex combination of mechanical, biochemical and biological properties of an HA cell scaffold. First, we optimized stiffness for a minimal reaction of adjacent brain to the transplant. Next hydrogel crosslinkers sensitive to matrix metalloproteinases (MMP) were incorporated as they promoted vascularization. Finally, candidate adhesion motifs and growth factors were systemically changed in vitro using a design of experiment approach to optimize stem cell survival or proliferation. The optimized HA hydrogel, tested in vivo, promoted survival of encapsulated human neural progenitor cells (iPS-NPCs) after transplantation into the stroke core and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. This HA hydrogel can be tracked in vivo with MRI. A hydrogel can serve as a therapeutic adjunct in a stem cell therapy through selective control of stem cell survival and differentiation in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain

et al. 2016

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“…The specific selection of HA as a hydrogel relies on its biocompatibility with human tissue, as it is constituted of naturally occurring brain extracellular matrix constituents. Furthermore, HA has been shown to enhance vessel growth in wound sites and to promote repair [5], [9]. The final purified product was lyophilized and stored at 4 °C until used.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach

Nih¹,

Moshayedi²,

Llorente³

et al. 2017

Data in Brief

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This article presents data related to the research article “Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain” (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016) [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA)-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs) after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1) Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2) the use of a design of Experiment (DOE) approach (M.W. 2 Weible and T. Chan-Ling, 2007) [2] to select multi-factorial experimental conditions, and (3) Inflammatory response and cell survival after transplantation.

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Approaches to the Development of Implantable Therapeutic Systems

Mane¹,

Maheshwari

Ghode

et al. 2019

Biomaterials and Bionanotechnology

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Development and in vivo evaluation of an implantable nano-enabled multipolymeric scaffold for the management of AIDS dementia complex (ADC)

Cited by 5 publications

References 37 publications

Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain

Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain

Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach

Approaches to the Development of Implantable Therapeutic Systems

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