Fabrication of Supramolecular Hydrogels for Drug Delivery and Stem Cell Encapsulation

Wu, Dequn; Wang, Tao; Lü, Bo; Xu, Xiaoding; Cheng, Si‐Xue; Jiang, Xuejun; Zhang, Xian‐Zheng; Zhuo, Ren‐Xi

doi:10.1021/la8006876

Cited by 144 publications

(116 citation statements)

References 44 publications

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“…Wang and coworkers prepared an injectable a-cyclodextrin/methoxypoly (ethylene glycol)-polycaprolactone-(dodecanedioic acid)-polycaprolactone-methoxypoly(ethylene glycol) (a-cyclodextrin/MPEG-PCL-MPEG) self-assembled hydrogel with a pore size of 50 mm, and encapsulated BM-MSCs in the supramolecular hydrogel to investigate the efficiency of cell transplantation for cardiac regeneration [148,149]. The injection of BM-MSCs with hydrogel increased the cell retention and vessel density around the infarct region, and improved the left ventricle ejection fraction compared with the cell injection alone.…”

Section: Stem Cell Differentiation To Myocytes On Polymeric Nanomatermentioning

confidence: 99%

Stem Cells and Nanostructures for Advanced Tissue Regeneration

Prabhakaran

Venugopal

Ghasemi‐Mobarakeh

et al. 2011

Biomedical Applications of Polymeric Nanofibers

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Stem cells are a promising alternative for cell therapy applications because of their self-renewing capability and potential to differentiate into a wide range of specialized cell lineages, including osteoblasts, chondrocytes, cardiomyocytes, and neuronal cells. Different kinds of stem cells are considered for cell-based tissue engineering approaches, of which bone-marrow-derived mesenchymal stem cells (BM-MSCs), adipose-derived stem cells (ADSCs) and embryonic stem cells (ESCs) are frequently utilized for advancement of new tissue engineering strategies. Nanostructures created by natural, synthetic, or composite polymeric biomaterials provide artificial templates of the extracellular matrix (ECM). They possess a high surface area to volume ratio, are porous with good mechanical properties, are sufficient to serve as a biomimetic platform to attract stem cells, cause differentiation, and provide functioning of the tissues. Nanoscale features such as fibers, pits, and grooves modulate cell behavior and might even stimulate the differentiation of stem cells to specific lineages; for example, the nanotopographical cues combined with chemical cues influence the neuronal induction of MSCs, resulting in high microtubule-associated protein expressions. Scaffolds can also be impregnated with several ligands for adhesion of receptors to the cells, or with other regulatory molecules and growth M.P. Prabhakaran (*) and J. Venugopal E3-05-12, Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore e-mail: nnimpp@nus.edu.sg L. Ghasemi-Mobarakeh Islamic Azad University, Najafabad Branch, Isfahan, Iran D. Kai NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore G. Jin and S. Ramakrishna Department of Mechanical Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore factors for designed cell behavior or controlled cell differentiations. Different polymeric blends or fibers incorporated with nanoparticles (such as hydroxyapatite) in aligned or custom-made patterns can induce specific differentiation of stem cells for bone, cartilage, cardiac, nerve, and skin tissue regeneration. In this review, we will discuss the current state of the art and future perspectives on stem cells and their differentiation on nanoengineered substrates for advanced tissue regeneration.

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Section: Stem Cell Differentiation To Myocytes On Polymeric Nanomatermentioning

confidence: 99%

Stem Cells and Nanostructures for Advanced Tissue Regeneration

Prabhakaran

Venugopal

Ghasemi‐Mobarakeh

et al. 2011

Biomedical Applications of Polymeric Nanofibers

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“…It is further envisaged that the incorporation of signaling or osteogenic factors within the core or shell part is a promising strategy for exogenous regulation of stem cell functions. 26 Compositional change of the core material is another strategy to improve the matrix properties for osteogenesis within the current design of the core-shell delivery system.…”

Section: Figmentioning

confidence: 99%

Utilizing Core–Shell Fibrous Collagen-Alginate Hydrogel Cell Delivery System for Bone Tissue Engineering

Pérez

Kim

et al. 2014

Tissue Engineering Part A

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Three-dimensional matrices that encapsulate and deliver stem cells with defect-tuned formulations are promising for bone tissue engineering. In this study, we designed a novel stem cell delivery system composed of collagen and alginate as the core and shell, respectively. Mesenchymal stem cells (MSCs) were loaded into the collagen solution and then deposited directly into a fibrous structure while simultaneously sheathing with alginate using a newly designed core-shell nozzle. Alginate encapsulation was achieved by the crosslinking within an adjusted calcium-containing solution that effectively preserved the continuous fibrous structure of the inner cell-collagen part. The constructed hydrogel carriers showed a continuous fiber with a diameter of *700-1000 mm for the core and 200-500 mm for the shell area, which was largely dependent on the alginate concentration (2%-5%) as well as the injection rate (20-80 mL/h). The water uptake capacity of the core-shell carriers was as high as 98%, which could act as a pore channel to supply nutrients and oxygen to the cells. Degradation of the scaffolds showed a weight loss of *22% at 7 days and *43% at 14 days, suggesting a possible role as a degradable tissue-engineered construct. The MSCs encapsulated within the collagen core showed excellent viability, exhibiting significant cellular proliferation up to 21 days with levels comparable to those observed in the pure collagen gel matrix used as a control. A live/dead cell assay also confirmed similar percentages of live cells within the core-shell carrier compared to those in the pure collagen gel, suggesting the carrier was cell compatible and was effective for maintaining a cell population. Cells allowed to differentiate under osteogenic conditions expressed high levels of bone-related genes, including osteocalcin, bone sialoprotein, and osteopontin. Further, when the core-shell fibrous carriers were implanted in a rat calvarium defect, the bone healing was significantly improved when the MSCs were encapsulated, and even more so after an osteogenic induction of MSCs before implantation. Based on these results, the newly designed core-shell collagen-alginate fibrous carrier is considered promising to enable the encapsulation of tissue cells and their delivery into damaged target tissues, including bone with defect-tunability for bone tissue engineering.

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“…Th e formation of supramolecular hydrogels from α-CD and PEO-PCL-PEO triblock copolymers has also been studied, and the resultant hydrogels have been used for the localized delivery of erythropoietin (EPO) in vitro and in vivo [55,56]. EPO can protect heart muscle tissue from ischemia-related damage, but it is also implicated in polycythaemia, which can cause thrombo-embolic complications.…”

Section: Review Articlementioning

confidence: 99%

“…Other biopolyester-based block copolymers have also been used for supramolecular hydrogel formation and for drug delivery applications [54][55][56]. A diblock copolymer of PEO with PCL was used to form a supramolecular hydrogel with α-CD, and the controlled-release properties of the hydrogel were studied using a model macromolecular drug [54].…”

Section: Block Copolymers Of Poly(ethylene Oxide) and Poly(ε-caprolacmentioning

confidence: 99%

Self-assembled supramolecular hydrogels based on polymer–cyclodextrin inclusion complexes for drug delivery

2010

NPG Asia Mater

130

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A supramolecular system is composed of two or more molecular entities held together and organized by means of intermolecular non-covalent binding interactions [1]. Supramolecular structures involving macrocyclic compounds have attracted tremendous interest not only as models for understanding natural supramolecular self-assembly and molecular recognition, but also as precursors for designing novel nanomaterials for electronics, biomedical and pharmaceutical applications [2][3][4][5][6][7][8][9][10][11]. Cyclodextrins (CDs), a series of natural cyclic oligosaccharides composed of 6, 7 or 8 d(+)-glucose units linked by d(+)-1,4-linkages (termed α-, β-and γ-CD, respectively), are well-suited for use in supramolecular systems. Th e geometry of CDs produces a hydrophobic inner cavity with a depth of ca. 7.0 Å and an internal diameter of ca. 4.5, 7.0 or 8.5 Å (α-, β-and γ-CD, respectively). Various molecules can be inserted into the cavities of CDs to form supramolecular inclusion complexes, and such systems have been studied extensively as models for understanding the mechanism of molecular recognition [12][13][14][15][16].A three-dimensional crosslinked network formed from a hydrophilic polymer, referred to as a hydrogel, can retain large volumes of water, causing the network to swell in solution. Th e extent of swelling and the content of water retained are largely dependent on the hydrophilicity of the polymer chains and the crosslinking density. Th e crosslinks can be formed by either covalent bonds or physical cohesion forces between the polymer segments, such as ionic bonds, hydrogen bonds, van der Waals forces and hydrophobic interactions [17][18][19][20]. Polymeric hydrogels are of great interest for biomaterials applications because of their biocompatibility [21,22], and due to their high water content, they are attractive for the delivery of delicate bioactive agents such as proteins [18,23,24]. For example, chemically crosslinked poly(ethylene oxide) (PEO) hydrogels have been studied extensively for this purpose [25][26][27]. However, requiring covalent crosslinking for gelation, many hydrogels can only be applied as implantables, and the incorporation of drugs by sorption may be time-consuming and provide only limited loading potential. For drug delivery, the crosslinking reaction may also conjugate the drug to the hydrogel or impair the drug's chemical integrity, while the hydrogel itself may become nonbiodegradable with an ill-defi ned composition. A delivery formulation in which gelation and drug loading can be achieved simultaneously in an aqueous environment and without covalent crosslinking is therefore an attractive prospect. Self-assembled supramolecular hydrogels based on polymer-cyclodextrin inclusion complexes for drug deliveryJun Li * National University of Singapore, SingaporeThe supramolecular self-assembly of cyclodextrins (CDs) and polymers has led to the development of novel supramolecular hydrogels for drug delivery applications. Many diff erent supramolecular hydrogels have been formed ...

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Fabrication of Supramolecular Hydrogels for Drug Delivery and Stem Cell Encapsulation

Cited by 144 publications

References 44 publications

Stem Cells and Nanostructures for Advanced Tissue Regeneration

Stem Cells and Nanostructures for Advanced Tissue Regeneration

Utilizing Core–Shell Fibrous Collagen-Alginate Hydrogel Cell Delivery System for Bone Tissue Engineering

Self-assembled supramolecular hydrogels based on polymer–cyclodextrin inclusion complexes for drug delivery

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