Triggered Drug Release from Dynamic Microspheres via a Protein Conformational Change

King, William J.; Pytel, Nicholas; Ng, Kelvin; Murphy, William L.

doi:10.1002/mabi.200900382

Cited by 30 publications

(28 citation statements)

References 18 publications

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“…Tailoring the ratio of PEG to CaM and the initial loading concentration modulated the release of VEGF from the hydrogel construct[115]. These materials have also been processed into microspheres loaded with VEGF and BMP-2 using an aqueous two-phase suspension polymerization[116]. Therapeutic proteins were released in a temporally controlled manner via ligand-induced conformational changes in the network.…”

Section: Cell or Tissue-dictated Stimuli For Dynamic Hydrogel Responsesmentioning

confidence: 99%

Hydrogels in healthcare: From static to dynamic material microenvironments

Kirschner¹,

Anseth²

2013

Acta Materialia

208

161

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Advances in hydrogel design have revolutionized the way biomaterials are applied to address biomedical needs. Hydrogels were introduced in medicine over 50 years ago and have evolved from static, bioinert materials to dynamic, bioactive microenvironments, which can be used to direct specific biological responses such as cellular ingrowth in wound healing or on-demand delivery of therapeutics. Two general classes of mechanisms, those defined by the user and those dictated by the endogenous cells and tissues, can control dynamic hydrogel microenvironments. These highly tunable materials have provided bioengineers and biological scientists with new ways to not only treat patients in the clinic but to study the fundamental cellular responses to engineered microenvironments as well. Here, we provide a brief history of hydrogels in medicine and follow with a discussion of the synthesis and implementation of dynamic hydrogel microenvironments for healthcare-related applications.

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Section: Cell or Tissue-dictated Stimuli For Dynamic Hydrogel Responsesmentioning

confidence: 99%

Hydrogels in healthcare: From static to dynamic material microenvironments

Kirschner¹,

Anseth²

2013

Acta Materialia

208

161

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“…Coupling the calmodulin into a PEGDA network created a hydrogel that could expand or collapse in response to trifluoropernazine, a small molecule drug that induces conformational change in calmodulin. This approach was used to release VEGF from PEG microspheres [307] and bulk hydrogels [308] in response to the ligand-induced conformational change. The PEG-calmodulin microspheres were implemented to release multiple growth factors, VEGF and BMP-2, which are especially relevant to bone tissue engineering [309].…”

Section: Spatially Controlled Delivery Technologiesmentioning

confidence: 99%

Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

Samorezov

Alsberg

2015

Advanced Drug Delivery Reviews

119

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Limitations of current treatment options for critical size bone defects create a significant clinical need for tissue engineered bone strategies. This review describes how control over the spatiotemporal delivery of growth factors, nucleic acids, and drugs and small molecules may aid in recapitulating signals present in bone development and healing, regenerating interfaces of bone with other connective tissues, and enhancing vascularization of tissue engineered bone. State-of-the-art technologies used to create spatially controlled patterns of bioactive factors on the surfaces of materials, to build up 3D materials with patterns of signal presentation within their bulk, and to pattern bioactive factor delivery after scaffold fabrication are presented, highlighting their applications in bone tissue engineering. As these techniques improve in areas such as spatial resolution and speed of patterning, they will continue to grow in value as model systems for understanding cell responses to spatially regulated bioactive factor signal presentation in vitro, and as strategies to investigate the capacity of the defined spatial arrangement of these signals to drive bone regeneration in vivo.

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“…5). King et al 50–52 encapsulated or absorbed growth factors within hydrogel microspheres, in which calmodulin was included as a functional component. The release rate of VEGF or bone morphogenetic protein-2 (BMP-2) from these microspheres was minimal in the absence of the trifluoperazine ligand.…”

Section: Applying Protein Motions: Toward Bio-responsive Drug Delimentioning

confidence: 99%

“…There are hundreds of protein motions that have been structurally characterized or modeled via predictive algorithms, 7,8 and many of these motions could be harnessed in future studies to build dynamic materials using design rules established in early studies to date. 38–42,48,50–52 However, it is noteworthy that the majority of these proteins are not ideal components of putative synthetic materials. Many natural dynamic proteins are too large to readily synthesize recombinantly, require multimerization for their dynamic function, or respond to a biochemical trigger only under very specific circumstances ( e.g.…”

Section: Emerging Directions: Mimicking and Exploiting Nature’s Prmentioning

confidence: 99%

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Emerging area: biomaterials that mimic and exploit protein motion

Murphy

2011

Soft Matter

Self Cite

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Traditional dynamic hydrogels have been designed to respond to changes in physicochemical inputs, such as pH and temperature, for a wide range of biomedical applications. An emerging strategy that may allow for more specific “bio-responsiveness” in synthetic hydrogels involves mimicking or exploiting nature’s dynamic proteins. Hundreds of proteins are known to undergo pronounced conformational changes in response to specific biochemical triggers, and these responses represent a potentially attractive toolkit for design of dynamic materials. This “emerging area” review focuses on the use of protein motions as a new paradigm for design of dynamic hydrogels. In particular, the review emphasizes early examples of dynamic hydrogels that harness well-known protein motions. These examples then serve as templates to discuss challenges and suggest emerging directions in the field. Successful early examples of this approach, coupled with the fundamental properties of nature’s protein motions, suggest that protein-based materials may ultimately achieve specific, multiplexed responses to a range of biochemical triggers. Applications of this new class of materials include drug delivery, biosensing, bioactuation, and tissue engineering.

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Triggered Drug Release from Dynamic Microspheres via a Protein Conformational Change

Cited by 30 publications

References 18 publications

Hydrogels in healthcare: From static to dynamic material microenvironments

Hydrogels in healthcare: From static to dynamic material microenvironments

Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

Emerging area: biomaterials that mimic and exploit protein motion

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