Production of heparin-functionalized hydrogels for the development of responsive and controlled growth factor delivery systems

Nie, Ting; Baldwin, Aaron D.; Yamaguchi, Nori; Kiick, Kristi L.

doi:10.1016/j.jconrel.2007.04.019

Cited by 215 publications

(197 citation statements)

References 46 publications

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“…Indeed, in our recent investigations, crosslinking of maleimide-functionalized heparin by thiol-terminated, linear PEGs of various molecular weights and compositions, affords gels with moduli ranging from 100s Pa to greater than 10 kPa, of appropriate range for a variety of soft tissue engineering applications. 84 These crosslinked, heparinized materials can bind GF and release them in a controlled fashion. These results suggest promising opportunities to combine these covalent strategies with the noncovalent crosslinking by GF to produce hydrogels that are responsive to a variety of biological stimuli, including proteolytic remodeling and ligand-receptor interactions.…”

Section: Discussionmentioning

confidence: 99%

Peptide- and protein-mediated assembly of heparinized hydrogels

Kiick

2008

Soft Matter

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Polymeric hydrogels have demonstrated significant promise in biomedical applications such as drug delivery and tissue engineering. A continued direction in hydrogel development includes the engineering of the biological responsiveness of these materials, via the inclusion of cell-binding domains and enzyme-sensitive domains. Ligand-receptor interactions offer additional opportunities in the design of responsive hydrogels, and strategies employing protein-polysaccharide interactions as a target may have unique relevance to materials intended to mimic the extracellular matrix (ECM). Accordingly, we have developed approaches for producing hydrogels via noncovalent interactions between heparin and heparin-binding peptides/proteins, and have demonstrated that such matrices are capable of both passive and receptor-mediated growth factor delivery. Further modification of these materials via the integration of these noncovalent strategies with chemical crosslinking methods will expand the range of their potential use and is under exploration. The combination of these approaches offers broad opportunities for the production of responsive matrices for biomedical applications.

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Section: Discussionmentioning

confidence: 99%

Peptide- and protein-mediated assembly of heparinized hydrogels

Kiick

2008

Soft Matter

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“…The adaptability of hydrogel synthesis allows one to introduce signalling molecules via covalent linkage, non-covalent tethering or physical entrapment 42 , or as localized depots 40,41,43 , leading to spatial morphogen gradients that mimic a common paradigm in tissue development and regeneration. Non-covalent tethering in a hydrogel can be used as a mechanism to control diffusivity of general classes of growth factors such as heparin binders 44 , or specific growth factors such as nerve growth factor 45 .…”

Section: Hydrogels That Degrade With Timementioning

confidence: 99%

Moving from static to dynamic complexity in hydrogel design

2012

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Hydrogels are water-swollen polymer networks that have found a range of applications from biological scaffolds to contact lenses. Historically, their design has consisted primarily of static systems and those that exhibit simple degradation. However, advances in polymer synthesis and processing have led to a new generation of dynamic systems that are capable of responding to artificial triggers and biological signals with spatial precision. These systems will open up new possibilities for the use of hydrogels as model biological structures and in tissue regeneration.H ydrogels are water-swollen polymer networks that have been used for many decades, with applications as varied as contact lenses and super-absorbant materials. As the field of biomedical engineering has developed, hydrogels have become a prime candidate for application as molecule delivery vehicles and as carriers for cells in tissue engineering, owing to their ability to mimic many aspects of the native cellular environment (for example, high water content, mechanical properties that match soft tissues). Traditional hydrogels, formed through the covalent and non-covalent crosslinking of polymer chains, were regarded as relatively inert materials, providing a simple biomimetic three-dimensional (3D) environment, either for tissue production by local resident cells or for positioning of cells delivered in vivo. However, the simplicity of these materials may have in fact hindered their application, restricting cellular interactions with the environment and preventing uniform extracellular matrix (ECM) production and proper tissue development. In addition, these materials were limited to modelling static environments and lacked the spatiotemporal dynamic properties relevant for complex tissue processes. Fortunately, during the last decade the concepts of hydrogel design and cellular interaction have evolved, shedding light on how they may control cell behaviour, particularly for tissue engineering applications.Hydrogels with a range of mechanical properties, and capable of incorporating a wide range of biologically relevant molecules, from individual functional groups to multidomain proteins, are currently in development 1 . In addition, hydrogels are being designed with spatial heterogeneity, to either replicate properties in native tissue structures or to produce constructs with distinct regionally specific cell behavior 2 . As a result, studies to date have clearly demonstrated the possibility of creating well-defined microenvironments with control over the 3D presentation of signals to cells 3 . However, recently there has been a focus on the concept of hydrogels that exhibit dynamic complexity. These materials should evolve with time and in response to

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“…Recently, many recent strategies have focused on composite hydrogels, which afford greater control over each of these aspects, by combining different degradable or non-degradable polymers with tailored chemistries in order to create bioactive systems with customized functional properties [3,4].…”

Section: Open Accessmentioning

confidence: 99%

Hydrogel-Based Platforms for the Regeneration of Osteochondral Tissue and Intervertebral Disc

et al. 2012

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Hydrogels currently represent a powerful solution to promote the regeneration of soft and hard tissues. Primarily, they assure efficient bio-molecular interactions with cells, also regulating their basic functions, guiding the spatially and temporally complex multi-cellular processes of tissue formation, and ultimately facilitating the restoration of structure and function of damaged or dysfunctional tissues. In order to overcome basic drawbacks of traditional synthesized hydrogels, many recent strategies have been implemented to realize multi-component hydrogels based on natural and/or synthetic materials with tailored chemistries and different degradation kinetics. Here, a critical review of main strategies has been proposed based on the use of hydrogels-based devices for the regeneration of complex tissues, i.e., osteo-chondral tissues and intervertebral disc.

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Production of heparin-functionalized hydrogels for the development of responsive and controlled growth factor delivery systems

Cited by 215 publications

References 46 publications

Peptide- and protein-mediated assembly of heparinized hydrogels

Peptide- and protein-mediated assembly of heparinized hydrogels

Moving from static to dynamic complexity in hydrogel design

Hydrogel-Based Platforms for the Regeneration of Osteochondral Tissue and Intervertebral Disc

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