DNA delivery from hyaluronic acid-collagen hydrogels via a substrate-mediated approach

Segura, Tatiana; Chung, Peter; Shea, Lonnie D.

doi:10.1016/j.biomaterials.2004.05.007

Cited by 146 publications

(131 citation statements)

References 38 publications

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“…Specific interactions can be introduced through complementary functional groups on the vector and surface, such as antigen-antibody or biotin-avidin [7][8][9]. Poly(L-lysine) (PLL) and polyethylenimine (PEI), modified with biotin residues, were complexed with DNA and bound to a neutravidin substrate [7,8], resulting in 100-fold increased transgene expression from the immobilized complexes relative to bolus delivery of complexes [7].…”

Section: Introductionmentioning

confidence: 99%

“…However, as in traditional gene delivery approaches, further improvements are still needed for substrate-mediated gene delivery to address issues that limit gene transfer, including complex size stability, complex aggregation and strong interactions between the surface and complexes [9,13]. Polyethylene glycol (PEG), which has the monomeric repeat unit [-CH 2 -CH 2 -O]-, is widely used in drug and gene delivery and has been incorporated into DNA complexes of several cationic polymers, including polymethacrylate [23], PEI [24][25][26][27][28][29][30][31][32], PLL [33][34][35] and poly(amidoamine)s [36].…”

Section: Introductionmentioning

confidence: 99%

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Surface polyethylene glycol enhances substrate-mediated gene delivery by nonspecifically immobilized complexes

2008

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Substrate-mediated gene delivery describes the immobilization of gene therapy vectors to a biomaterial, which enhances gene transfer by exposing adhered cells to elevated DNA concentrations within the local microenvironment. Surface chemistry has been shown to affect transfection by nonspecifically immobilized complexes using self-assembled monolayers (SAMs) of alkanethiols on gold. In this report, SAMs were again used to provide a controlled surface to investigate whether the presence of oligo(ethylene glycol) (EG) groups in a SAM could affect complex morphology and enhance transfection. EG groups were included at percentages that did not affect cell adhesion. Nonspecific complex immobilization to SAMs containing combinations of EG-and carboxylic acidterminated alkanethiols resulted in substantially greater transfection than surfaces containing no EG groups or SAMs composed of EG groups combined with other functional groups. Enhancement in transfection levels could not be attributed to complex binding densities or release profiles. Atomic force microscopy imaging of immobilized complexes revealed that EG groups within SAMs affected complex size and appearance and could indicate the ability of these surfaces to preserve complex morphology upon binding. The ability to control the morphology of the immobilized complexes and influence transfection levels through surface chemistry could be translated to scaffolds for gene delivery in tissue engineering and diagnostic applications.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Surface polyethylene glycol enhances substrate-mediated gene delivery by nonspecifically immobilized complexes

2008

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“…HA-based hydrogels with surface associated neutravidin was able to bind biotinylated PEI/DNA complexes [111]. Similarly, collagen and polyurethane films modified with anti-adenovirus antibodies were employed to binding adenoviruses, with [99] or without [112] the avidin/biotin chemistry.…”

Section: Vector Immobilizationmentioning

confidence: 99%

Matrices and scaffolds for DNA delivery in tissue engineering

Laporte¹,

Shea²

2007

Advanced Drug Delivery Reviews

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240

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Regenerative medicine aims to create functional tissue replacements, typically through creating a controlled environment that promotes and directs the differentiation of stem or progenitor cells, either endogenous or transplanted. Scaffolds serve a central role in many strategies by providing the means to control the local environment. Gene delivery from the scaffold represents a versatile approach to manipulating the local environment for directing cell function. Research at the interface of biomaterials, gene therapy, and drug delivery has identified several design parameters for the vector and the biomaterial scaffold that must be satisfied. Progress has been made towards achieving gene delivery within a tissue engineering scaffold, though the design principles for the materials and vectors that produce efficient delivery require further development. Nevertheless, these advances in obtaining transgene expression with the scaffold have created opportunities to develop greater control of either delivery or expression and to identify the best practices for promoting tissue formation. Strategies to achieve controlled localized expression within the tissue engineering scaffold will have broad application to the regeneration of many tissues, with great promise for clinical therapies.

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“…For gene delivery in particular, localized release of plasmid or DNA complexes can transfect cells for the sustained production of tissue inductive proteins [9,10]. Hydrogels formed from a range of polymers have been employed for the controlled release non-viral vectors, such as naked plasmid or cationic polymer/DNA complexes [4,[11][12][13][14][15][16]. For many hydrogels, release occurs primarily by diffusion, which can be influenced by physical properties such as water content, swelling ratio, and mesh size.…”

Section: Introductionmentioning

confidence: 99%

“…Many naturally occurring biopolymers, such as hyaluronic acid (HA) [2] and collagen [3,4], are generally considered to be biocompatible and can be used alone or in combination with synthetic polymers such as poly(ethylene glycol) (PEG). The natural polymers provide specific biological interactions or functionality, whereas the synthetic polymers can modulate the physical properties and can be synthesized cost effectively and reproducibly [2].…”

Section: Introductionmentioning

confidence: 99%

Non-viral vector delivery from PEG-hyaluronic acid hydrogels

Wieland

Houchin-Ray

Shea

2007

Journal of Controlled Release

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121

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Hydrogels have been widely used in tissue engineering as a support for tissue formation or to deliver non-viral gene therapy vectors locally. Hydrogels that combine these functionalities can provide a fundamental tool to promote specific cellular processes leading to tissue formation. This report investigates controlled release of gene therapy vectors from hydrogels as a function of the physical properties for both the hydrogel and the vector. Hydrogels were formed by photocrosslinking acrylmodified hyaluronic acid (HA) with a 4-arm poly(ethylene glycol) (PEG) acryl. The polymer content, and relative composition of HA and PEG modulated the swelling ratio, water content, and degradation, which can influence transport of the vector through the hydrogel. All hydrogels had a water content of 94% or higher, though the water content and swelling ratio increased with a decrease in the PEG:HA ratio. Plasmids were stably incorporated into the hydrogel, with a majority of the release occurring during the initial 2 days. For incubation in buffer, the cumulative release increased with a decreasing PEG or increasing HA content, with approximately 20% to 80% released during the first week depending on the hydrogel composition. Hydrogels incubated in hyaluronidase, an enzyme that degrades HA, significantly increased plasmid release for hydrogels containing 4% PEG and 4% HA-Acryl. The encapsulation of plasmid complexed with polyethylenimine had less than 14% of the complexes released from the hydrogel both in the presence and absence of hyaluronidase. The limited release of the complexes likely results from the complex size and interactions between the vector and hydrogel. These studies demonstrate the dependence of non-viral vector release on the physical properties of the hydrogel and the vector, suggesting vector and hydrogel designs for maximizing localized delivery of non-viral vectors.

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DNA delivery from hyaluronic acid-collagen hydrogels via a substrate-mediated approach

Cited by 146 publications

References 38 publications

Surface polyethylene glycol enhances substrate-mediated gene delivery by nonspecifically immobilized complexes

Surface polyethylene glycol enhances substrate-mediated gene delivery by nonspecifically immobilized complexes

Matrices and scaffolds for DNA delivery in tissue engineering

Non-viral vector delivery from PEG-hyaluronic acid hydrogels

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