PEG Hydrogels for the Controlled Release of Biomolecules in Regenerative Medicine

Lin, Chien‐Chi; Anseth, Kristi S.

doi:10.1007/s11095-008-9801-2

Cited by 903 publications

(771 citation statements)

References 125 publications

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“…Extracellular matrix-based materials, such as collagen-glycosaminoglycan scaffolds and hyaluronic acid hydrogels, have also been explored with cells that are seeded before grafting (9,10). Softer materials, including hydrogel-based delivery systems, can effectively present biological cues, such as growth factors at low doses (11,12). A range of BMP-2 doses have been explored from biomaterial carriers-from 100 ng to 2 mg in ratsand bone regeneration was observed at all of these doses (13).…”

Section: Significancementioning

confidence: 99%

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

Shah

Hyder

Quadir

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

131

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Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration.regenerative medicine | layer-by-layer | biomaterial | controlled drug release | wound healing

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Section: Significancementioning

confidence: 99%

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

Shah

Hyder

Quadir

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

131

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Section: Poly-ethylene-glycol (Peg)/poly-ethylene Oxide (Peo)mentioning

confidence: 99%

“…it can be used for cell immobilization [127] and drug release [128] . Another interesting capability of PEG is that it has anti-oxidant actions [129,130] , which may limit secondary injury.…”

Section: Poly-ethylene-glycol (Peg)/poly-ethylene Oxide (Peo)mentioning

confidence: 99%

“…Another interesting capability of PEG is that it has anti-oxidant actions [129,130] , which may limit secondary injury. PEG hydrogels have been used alone [119-123, 129, 130] and as factors [128] or cellular carriers [131] after SCi and they are generally considered promising candidates for nervous tissue repair.Poly(vinyl alcohol) (PVA) PVA is a degradable, biocompatible, non-toxic, carbon-carbon backbone polymer [132] , which makes it an attractive option for biomedical applications. it is nontoxic, hydrophilic, and has good adhesion properties.…”

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confidence: 99%

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Biomaterials for spinal cord repair

Haggerty

Oudega

2013

Neurosci. Bull.

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Spinal cord injury (SCi) results in permanent loss of function leading to often devastating personal, economic and social problems. A contributing factor to the permanence of SCi is that damaged axons do not regenerate, which prevents the re-establishment of axonal circuits involved in function. Many groups are working to develop treatments that address the lack of axon regeneration after SCi. The emergence of biomaterials for regeneration and increased collaboration between engineers, basic and translational scientists, and clinicians hold promise for the development of effective therapies for SCi. A plethora of biomaterials is available and has been tested in various models of SCi. Considering the clinical relevance of contusion injuries, we primarily focus on polymers that meet the specific criteria for addressing this type of injury. Biomaterials may provide structural support and/or serve as a delivery vehicle for factors to arrest growth inhibition and promote axonal growth. Designing materials to address the specific needs of the damaged central nervous system is crucial and possible with current technology. Here, we review the most prominent materials, their optimal characteristics, and their potential roles in repairing and regenerating damaged axons following SCi.Keywords: spinal cord injury; axon regeneration; biodegradable materials; extracellular matrix proteins; functional recovery; growth factor; guidance; injury and repair; spinal motor neuron IntroductionSpinal cord injury (SCi) causes loss of neurons and axons resulting in motor and sensory function impairments. There are thousands of new cases of SCi in the world annually [1,2] occurring often in young adults. The lack of endogenous repair and the significant costs to the individual, family and society [1] are important motivations behind the continuing efforts to develop effective therapies. Promoting axonal regeneration is considered a potential repair strategy because it could lead to recovery of axonal circuits involved in motor and/or sensory function [3] .The central nervous system (CNS) neurons are intrinsically capable of some regeneration of damaged axons [4] but their attempts after SCi are frustrated by structural and chemical obstructions in the damaged nervous tissue [5] . Spinal cord repair approaches typically lead to small functional gains. one feature that most of these approaches have in common is a poor axonal regeneration response, suggesting that promoting axonal regeneration, including synapse formation, is essential to achieve substantial functional repair after SCi. if so, it is rational to anticipate that effective spinal cord therapies will need to include interventions addressing the axon growth-inhibition that leads to the poor axonal growth responses. As introduced above, axonal regeneration is considered an important repair mechanism for the injured spinal cord. Therefore, this review focuses on materials that have shown most promise to elicit an axonal regeneration response to foster functional restoration after ...

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“…[1][2][3][4][5][6][7][8] To be incorporated into a hydrogel structure, the hydroxyl end group of PEG is usually and conveniently reacted with acryloyl chloride to form an acrylate structure (PEG-A, Scheme 1), [9][10][11] which subsequently undergoes either a free radical polymerization or the Michael-type addition reaction with thiol-containing molecules. [11][12][13][14] Consequently, the formed hydrogel structure contains ester linkages at the crosslink points, and their hydrolysis (half time of the ester bonds in the water-rich environment is on the order of days at pH 7.4 and 37 C) will result in disintegration of the gel, [15][16][17] which is an advantage for applications requiring gel degradation but a disadvantage for longer term applications such as vitreous, cartilage, and nucleus pulposus replacement.…”

mentioning

confidence: 99%

A new end group structure of poly(ethylene glycol) for hydrolysis‐resistant biomaterials

Tong

Lai

Guo

et al. 2011

J. Polym. Sci. A Polym. Chem.

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INTRODUCTION Because of their excellent biocompatibility, poly(ethylene glycol) (PEG) and its derivatives have been widely used in biomedical applications, especially in drug PEGylation, biomaterial surface modification, and hydrogelbased implants and tissue scaffolds. [1][2][3][4][5][6][7][8] To be incorporated into a hydrogel structure, the hydroxyl end group of PEG is usually and conveniently reacted with acryloyl chloride to form an acrylate structure (PEG-A, Scheme 1), 9-11 which subsequently undergoes either a free radical polymerization or the Michael-type addition reaction with thiol-containing molecules. 11-14 Consequently, the formed hydrogel structure contains ester linkages at the crosslink points, and their hydrolysis (half time of the ester bonds in the water-rich environment is on the order of days at pH 7.4 and 37 C) will result in disintegration of the gel, 15-17 which is an advantage for applications requiring gel degradation but a disadvantage for longer term applications such as vitreous, cartilage, and nucleus pulposus replacement.

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PEG Hydrogels for the Controlled Release of Biomolecules in Regenerative Medicine

Cited by 903 publications

References 125 publications

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

Biomaterials for spinal cord repair

A new end group structure of poly(ethylene glycol) for hydrolysis‐resistant biomaterials

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