Rapid, Guanosine 5'‐Diphosphate‐Induced, Gelation of Chitosan Sponges as Novel Injectable Scaffolds for Soft Tissue Engineering and Drug Delivery Applications

Mekhail, Mina; Daoud, Jamal; Almazán, Guillermina; Tabrizian, Maryam

doi:10.1002/adhm.201200371

Cited by 23 publications

(26 citation statements)

References 37 publications

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“…20−22 Because of their good biocompatibility and controllable biodegradability, natural materials have been widely used for injectable hydrogels for drug delivery. 23,24 Sodium alginate, a naturally occurring nontoxic polysaccharide derived from brown seaweed, is one of the most versatile natural polymers used in the medical and cosmetics fields. 25,26 Alginate has been fabricated into large beads, microbeads, block gels, fibers, and in situ gelling systems.…”

Section: ■ Introductionmentioning

confidence: 99%

Multifunctional Interpenetrating Polymer Network Hydrogels Based on Methacrylated Alginate for the Delivery of Small Molecule Drugs and Sustained Release of Protein

et al. 2014

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Multifunctional injectable thermo-/pH-responsive hydrogels as release systems for the oral delivery of small molecule drugs and the local delivery of protein are presented. The injectable interpenetrating polymer network (IPN) hydrogels based on poly(ethylene glycol) methacrylate, N-isopropylacrylamide, and methacrylated alginate were prepared by using ammonium persulfate (APS) and N,N,N',N'-tetramethylethylenediamine (TEMED) as a redox initiator system at body temperature, and the obtained hydrogels overcame the instability of calcium cross-linked alginate hydrogels under physiological conditions. The hydrogels showed good mechanical strength by rheometer and exhibited temperature and pH sensitivity by a swelling test. Diclofenac sodium (DCS) as a model for small molecule water-soluble anti-inflammatory drugs and bovine serum albumin (BSA) as a model for protein drugs were encapsulated in situ in the hydrogel. The DCS and BSA release results indicated that these hydrogels, as carriers, have great potential for use in the oral delivery of small molecule drugs and for long-term localized protein release. Furthermore, the cytotoxicity of these hydrogels was studied via live/dead viability and alamarBlue assays using adipose tissue-derived mesenchymal stem cells.

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Section: ■ Introductionmentioning

confidence: 99%

Multifunctional Interpenetrating Polymer Network Hydrogels Based on Methacrylated Alginate for the Delivery of Small Molecule Drugs and Sustained Release of Protein

et al. 2014

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“…The higher encapsulation efficiency was attributed to the higher water retention of C3PH5, which allows for the entrapment of more BDNF. Moreover, using a higher concentration of chitosan in C6PH6 lead to the formation of a denser chitosan network, with less water retention and thus a slower release of BDNF [3]. At day 16, C3PH5 released 19% of the encapsulated BDNF, while C6PH6 only released 11%.…”

Section: Discussionmentioning

confidence: 99%

“…The pH of the 3 mg/ml chitosan solution was raised to 5, and the pH of the 6 mg/ml solution was raised to 6 using a 1M sodium bicarbonate solution; these two solutions were given the acronyms C3PH5 and C6PH6 respectively [3]. The solutions were sterilized by filtration through 0.22 μm syringe filters and 1.7 ml from each solution was placed into Lo-Bind Eppendorfs.…”

Section: Preparation Of Gdp-crosslinked Sponges and Bdnf Encapsulationmentioning

confidence: 99%

“…Failure to fully remyelinate has been attributed to the inability of OPCs to fully differentiate into mature OGs [2]. The aim of this work was to address this issue through developing a rapidly-gelling, injectable chitosan sponge that is crosslinked using Guanosine 5'-diphosphate (GDP) to promote human OPC differentiation [3]. The rapid gelation (T gel < 2 seconds) occurs due to the electrostatic interactions between cationic amine groups in chitosan and anionic phosphate groups in GDP.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, OPCs have been shown to be mechano-sensitive, and therefore having a biomaterial with close to native mechanical properties is highly desirable for their attachment and differentiation [4]. The compressive moduli of elasticity of the sponges have been assessed in a previous publication using a spherical indenter and a miniature loading stage [3]. The moduli of elasticity ranged from 0.87 ± 0.093 MPa and 0.43 ± 0.048 depending on the sponge formulation, which is very close to the stiffness of the spinal cord reported in the literature [5,6].…”

Section: Introductionmentioning

confidence: 99%

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A Novel Injectable Chitosan Sponge Containing Brain Derived Neurotrophic Factor (BDNF) to Enhance Human Oligodendrocyte Progenitor Cells' (OPC) Differentiation

Mekhail

Cui²,

Almazán³

et al. 2014

MRS Proc.

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We developed a rapidly-gelling chitosan sponge crosslinked with Guanosine 5'-Diphosphate (GDP). GDP has not been previously explored as an anionic crosslinker, and it was used in this application since the nucleoside guanosine has been shown to improve remyelination in situ, and thus its presence in the sponge composition was hypothesized to induce Oligodendrocyte Progenitor Cells' (OPC) differentiation. In addition to the chemical composition tailored to target OPCs, the developed chitosan sponge possesses a wide range of desirable physicochemical properties such as: rapid gelation, high porosity with interconnected pores, moduli of elasticity resembling that of soft tissue and cytocompatibility with many cell types. Moreover, protein encapsulation into the sponges was possible with high encapsulation efficiencies (e.g. BMP-7 and NT-3). In this study, BDNF was encapsulated in the chitosan sponges with an encapsulation efficiency greater than 80% and a sustained release over a 16-day period was achieved. We demonstrate here for the first time, the attachment of human fetal OPCs to the sponges and their differentiation after 12 days of culture. Overall, this newly-introduced injectable sponge is a promising therapeutic modality that can be used to enhance remyelination post-spinal cord injuries.

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Injectable Chitosan‐Based Scaffolds in Regenerative Medicine and their Clinical Translatability

Mekhail¹,

Tabrizian²

2014

Adv Healthcare Materials

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Injectable scaffolds (IS) are polymeric solutions that are injected in vivo and undergo gelation in response to physiological or non-physiological stimuli. Interest in using IS in regenerative medicine has been increasing this past decade. IS are administered in vivo using minimally invasive surgery, which reduces hospitalization time and risk of surgical wound infection. Here, chitosan is explored as an excellent candidate for developing IS. A literature search reveals that 27% of IS publications in the past decade investigated injectable chitosan scaffolds (ICS). This increasing interest in chitosan stems from its many desirable physicochemical properties. The first section of this Progress Report is a comprehensive study of all physical, chemical, and biological stimuli that have been explored to induce ICS gelation in vivo. Second, the use of ICS is investigated in four major regenerative medicine applications, namely bone, cartilage, cardiovascular, and neural regeneration. Finally, an overall critique of the ICS literature in light of clinical translatability is presented. Even though ICS have been widely explored in the literature, very few have progressed to clinical trials. The authors discuss the current barriers to moving ICS into the clinic and provide suggestions regarding what is needed to overcome those challenges.

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Rapid, Guanosine 5'‐Diphosphate‐Induced, Gelation of Chitosan Sponges as Novel Injectable Scaffolds for Soft Tissue Engineering and Drug Delivery Applications

Cited by 23 publications

References 37 publications

Multifunctional Interpenetrating Polymer Network Hydrogels Based on Methacrylated Alginate for the Delivery of Small Molecule Drugs and Sustained Release of Protein

Multifunctional Interpenetrating Polymer Network Hydrogels Based on Methacrylated Alginate for the Delivery of Small Molecule Drugs and Sustained Release of Protein

A Novel Injectable Chitosan Sponge Containing Brain Derived Neurotrophic Factor (BDNF) to Enhance Human Oligodendrocyte Progenitor Cells' (OPC) Differentiation

Injectable Chitosan‐Based Scaffolds in Regenerative Medicine and their Clinical Translatability

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