Systemic administration of enzyme-responsive growth factor nanocapsules for promoting bone repair

Qi, Hongzhao; Yang, Lijun; Li, Xueping; Sun, Xiaolei; Zhao, Jin; Hou, Xin; Li, Zhaoyang; Yuan, Xubo; Cui, Zhenduo; Yang, Xianjin

doi:10.1039/c8bm01632a

Cited by 38 publications

(27 citation statements)

References 39 publications

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“…As a result, the formed nanocapsules sustained local GF concentration and reduced systemic side effects in rat tibial injury model. [ 98 ] Anjum et al demonstrated a modularly assembled, transglutaminase‐crosslinked poly(ethylene glycol) (TG‐PEG) and MMP Lysine‐peptide grafted chondroitin sulfate (CS) precursor (CS‐MMP‐Lys) hybrid hydrogel platform (CS‐PEG) to tune BMP‐2 binding and release to induce bone regeneration. [ 99 ] Holloway et al developed a material that concurrently delivered SDF‐1α and BMP‐2 through a hydrogel composed of a maleimide‐modified hyaluronic acid (MaHA) combined with both cell‐adhesive peptides (RGD, pendent) and MMP‐sensitive peptides (VPMS↓MRGG, crosslinker).…”

Section: Stimuli‐responsive Growth Factor Delivery Systems In Tissue mentioning

confidence: 99%

Stimuli‐Responsive Delivery of Growth Factors for Tissue Engineering

Jiang

Zhou

et al. 2020

Adv Healthcare Materials

105

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Growth factors (GFs) play a crucial role in directing stem cell behavior and transmitting information between different cell populations for tissue regeneration. However, their utility as therapeutics is limited by their short half‐life within the physiological microenvironment and significant side effects caused by off‐target effects or improper dosage. “Smart” materials that can not only sustain therapeutic delivery over a treatment period but also facilitate on‐demand release upon activation are attracting significant interest in the field of GF delivery for tissue engineering. Three properties are essential in engineering these “smart” materials: 1) the cargo vehicle protects the encapsulated therapeutic; 2) release is targeted to the site of injury; 3) cargo release can be modulated by disease‐specific stimuli. The aim of this review is to summarize the current research on stimuli‐responsive materials as intelligent vehicles for controlled GF delivery; Five main subfields of tissue engineering are discussed: skin, bone and cartilage, muscle, blood vessel, and nerve. Challenges in achieving such “smart” materials and perspectives on future applications of stimuli‐responsive GF delivery for tissue regeneration are also discussed.

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Section: Stimuli‐responsive Growth Factor Delivery Systems In Tissue mentioning

confidence: 99%

Stimuli‐Responsive Delivery of Growth Factors for Tissue Engineering

Jiang

Zhou

et al. 2020

Adv Healthcare Materials

105

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“…In addition, we have proven that proteins are not modified during polymerization. As an example, bone morphogenetic protein-2 (BMP-2) can be released from nanogels without any damage [4]. Therefore, this kind of nanogels is an excellent alternative for protein encapsulation.…”

Section: The Activity Of Native Catalase and Paam-n(catalase)mentioning

confidence: 99%

“…The protection ability of nanogels was mainly dependent on the polymeric shells formed by monomers [42,43]. Therefore, through changing the crosslinkers, we could also design the responsive-release nanogels with high protection ability to load other functional protein drugs, such as monoclonal antibodies [44] and growth factors [4], on scaffolds with organic coatings. In other words, we exploited a platform for the loading of protein drugs on scaffolds using organic coatings.…”

Section: The Detection Of the Ros Concentration In 4t1 Cellsmentioning

confidence: 99%

“…Most protein drugs, such as monoclonal antibodies [3], are currently used as injection formulations. However, the moderate bioavailability of protein drugs often results in their low concentration in the lesion after systemic administration [4]. Therefore, many organic or inorganic scaffolds are currently under investigation for the local controlled release of protein drugs [5,6].…”

Section: Introductionmentioning

confidence: 99%

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The Stability Maintenance of Protein Drugs in Organic Coatings Based on Nanogels

Yang

Shan

et al. 2020

Pharmaceutics

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Protein drugs are often loaded on scaffolds with organic coatings to realize a spatiotemporal controlled release. The stability or activity of protein drugs, however, is largely affected by the organic coating, particularly with organic solvents, which can dramatically reduce their delivery efficiency and limit their application scope. In spite of this, little attention has been paid to maintaining the stability of protein drugs in organic coatings, to date. Here, we used catalase as a model protein drug to exploit a kind of chemically cross-linked nanogel that can efficiently encapsulate protein drugs. The polymeric shells of nanogels can maintain the surface hydration shell to endow them with a protein protection ability against organic solvents. Furthermore, the protection efficiency of nanogels is higher when the polymeric shell is more hydrophilic. In addition, nanogels can be dispersed in polylactic acid (PLA) solution and subsequently coated on scaffolds to load catalase with high activity. To the best of our knowledge, this is the first use of hydrophilic nanogels as a protection niche to load protein drugs on scaffolds through an organic coating, potentially inspiring researchers to exploit new methods for protein drug loading.

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“…Major shortcomings include short half‐lives in circulation, susceptibility to deactivation and degradation by enzymes, and rapid rates of internalization. [ 5,10,11 ] For example, the half‐life of vascular endothelial growth factor (VEGF) after intravenous injection is only 50 min, while that of FGF‐2 is merely 3 min. [ 5 ] This has led to the requirement of a regimen of repeated systemic administration at supraphysiologic doses, in order to achieve sustained effective local concentrations.…”

Section: Introductionmentioning

confidence: 99%

Biomaterials for Sequestration of Growth Factors and Modulation of Cell Behavior

Teixeira

Domingues

Shevchuk

et al. 2020

Adv Funct Materials

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Growth factors (GFs) are proteins secreted by cells that regulate a variety of biological processes. Although they have long been proposed as potent therapeutic agents, their administration in a soluble form has proven costly and ineffective due to their short half-lives in biological environments. Biomaterial-based approaches are increasingly sought as alternatives to improve the efficacy or, ideally, replace the need for exogenous administration of GFs in regenerative medicine strategies. The means by which these systems evolve from biomaterials for conventional controlled release of GFs to the recent extracellular matrix (ECM)-inspired approaches for sequestering these labile molecules and regulating their spatiotemporal activity and presentation are reviewed. Focus is placed on biomaterials functionalized either with ECM components, which show promiscuous GF binding, or with targeted GF ligands (antibodies, aptamers, or peptides). The potential of synthetic platforms with abiotic affinity as cost-effective alternatives to the current biological ligands is also discussed. Overall, the various GF sequestering systems developed so far have remarkably improved the activity of GFs at reduced doses and, in some cases, completely avoided the need for their exogenous administration to guide cell fates. These bioinspired concepts thus enable the rational exploration of the full therapeutic potential of GFs in regenerative medicine.

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Systemic administration of enzyme-responsive growth factor nanocapsules for promoting bone repair

Abstract: Taking the advantages of the unique physiological character of bone fracture, a systemic delivery platform of growth factors for bone repair based on nanocapsules was exploited.

Cited by 38 publications

References 39 publications

Stimuli‐Responsive Delivery of Growth Factors for Tissue Engineering

Stimuli‐Responsive Delivery of Growth Factors for Tissue Engineering

The Stability Maintenance of Protein Drugs in Organic Coatings Based on Nanogels

Biomaterials for Sequestration of Growth Factors and Modulation of Cell Behavior

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