The pro-angiogenic characteristics of a cross-linked gelatin matrix

The aim of this study was to investigate the effects of local administration of fluvastatin-gelatin complex on the healing of bone defects in low-turnover osteoporosis mice. Gelatin was used as a carrier of the fluvastatin. A fluvastatin-gelatin complex solution was created by dissolving each concentration of fluvastatin in a 75mg/mL gelatin solution. The gelatin solution was mixed with air, then lyophilized for 1 day and crosslinked by dry heating to make a fluvastatin-gelatin complex sponge. After crosslinking, the complex sponge was cut into pieces 1 mm diameter × 1 mm high to fit the bone defect area. The amount of fluvastatin in the sponge was adjusted to control (0 nmol), 0.1 nmol, 0.2 nmol, and 0.4 nmol. Using 20-week-old low-turnover osteoporosis model mice (SAMP6) and normal model mice (SAMR1), cylindrical and bone defects were made in sites 1.0 mm in diameter and depth, 1 mm of 3 mm from both sides of the distal end of the femur. The complex sponge was then inserted into each site, and the wound was closed. Radiographic analysis and histologic examinations were then performed. In SAMP6, the bone volumes of the bone defect areas in the 0.1nmol and 0.2nmol groups were significantly higher compared with those of the control and 0.4nmol groups at 14 and 21 days. Histological observation showed that the volume of newly formed bone increased in the 0.1nmol and 0.2nmol groups compared to those in the control and 0.4nmol groups at 14 and 21 days. The bone volumes of newly formed bone in SAMR1 were higher than were those in SAMP6, and the optimum concentration of fluvastatin was different between SAMP6 and SAMR1. The present study suggests that local administration of a fluvastatin-gelatin complex sponge provides improvement in bone healing in low-turnover osteoporosis.

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“…The release characteristics of fluvastatin from the fluvastatingelatin complex sponge were investigated in previous studies 15,16) .…”

Section: Discussionmentioning

confidence: 99%

Effect of Locally Applied Fluvastatin in Low-turnover Osteoporosis Model Mouse with Femur Bone Defect

Ohira

Koji

Sasaki

et al. 2015

J. Hard Tissue Biology.

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“…Due to the structural similarity of alginate to ECM , these gels are 70 used in cell delivery vehicles 13 , matrices for tissue engineering 14 , drug delivery beads and ECM models for cell experiments 15 . Gelatin, a denatured type of collagen, has been widely used in wound dressing, as pro-angiogenic matrices and absorbents pads for surgical applications [16][17][18] . At physiological temperature 75 (37ºC), gelatin is a solution, but can reversibly form a gel when cooled (< 29 ºC).…”

mentioning

confidence: 99%

Bio-ink properties and printability for extrusion printing living cells

et al. 2013

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Additive biofabrication (3D bioprinting) makes it possible to create scaffolds with precise geometries, control over pore interconnectivity and architectures that are not possible with conventional techniques. Inclusion of cells within the ink to form a "bio-ink" presents the potential to print 3D structures that can be implanted into damaged/diseased tissue to promote highly controlled cell-based regeneration and repair. The properties of an 'ink' are defined by its formulation and critically influence the delivery and integrity of structure formed. Importantly, the ink properties need to conform to biological requirements necessary for the cell system that they are intended to support and it is often challenging to find conditions for printing that facilitate this critical aspect of tissue bioengineering. In this study, alginate (Alg) was selected as the major component of the 'bio-ink' formulations for extrusion printing of cells. The rheological properties of alginate-gelatin (AlgGel) blends were compared with pre-crosslinked alginate and alginate solution to establish their printability whilst maintaining their ability to support optimal cell growth. Pre-crosslinked alginate on its own was liquidlike during printing. However, by controlling the temperature, Alg-Gel formulations had higher viscosity, storage modulus and consistency which facilitated higher print resolution/precision. Compression and indentation testing were used to examine the mechanical properties of alginate compared to Alg-Gel. Both types of gels yielded similar results with modulus increasing with alginate concentration. Decay in mechanical properties over time suggests that Alg-Gel slowly degrades in cell culture media with more than 60% decrease in initial modulus over 7 days. The viability of primary myoblasts delivered as a myoblast/Alg-Gel bio-ink was not affected by the printing process, indicating that the Alg-Gel matrix provides a potential means to print 3D constructs that may find application in myoregenerative applications. control over pore interconnectivity and architectures that are not possible with conventional techniques. Inclusion of cells within the ink to form a "bio-ink" presents the potential to print 3D structures that can be implanted into damaged/diseased tissue to promote highly controlled cell-based regeneration and repair. The properties of an 'ink' are defined by its formulation and critically influence the delivery and integrity of structure formed. Importantly, the ink properties need to conform to biological requirements 10 necessary for the cell system that they are intended to support and it is often challenging to find conditions for printing that facilitate this critical aspect of tissue bioengineering. In this study, alginate (Alg) was selected as the major component of the 'bio-ink' formulations for extrusion printing of cells. The rheological properties of alginate-gelatin (Alg-Gel) blends were compared with pre-crosslinked alginate and alginate solution to establish their printability whil...

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“…44 Although there are many reported methods for covalently crosslinking gelatin, photocrosslinking GelMA has been shown to be both compatible with cellular encapsulation and microfabrication. 3,23 Aside from the above-mentioned biological qualities that gelatin displays, previous research has highlighted the trophic effects of gelatin, exhibiting proangiogenic properties and promotion of valvular interstitial cell function.…”

mentioning

confidence: 99%

“…3,23 Aside from the above-mentioned biological qualities that gelatin displays, previous research has highlighted the trophic effects of gelatin, exhibiting proangiogenic properties and promotion of valvular interstitial cell function. 3,44 The supplementation of PEG hydrogels with GelMA has led to the development of a photocrosslinkable hydrogel that is inexpensive, easily produced with common equipment and chemicals, and biologically and mechanically tunable. GelMA enhanced the compressive modulus of 5% (w/v) and 10% (w/v) PEG, exceeding the compressive modulus of PEG and GelMA alone.…”

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confidence: 99%

“…3, 44 The addition of GelMA allowed NIH3T3 fibroblasts to remodel their environment, creating cellular networks within the composite hydrogels at 7 days post-encapsulation. Although PEG was functionalized in this study through the addition of GelMA, conceivably any water-soluble hydrogel that polymerizes using acrylate chemistry could be functionalized with the addition of GelMA.…”

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confidence: 99%

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Synthesis and Characterization of Tunable Poly(Ethylene Glycol): Gelatin Methacrylate Composite Hydrogels

Hutson

Nichol

Aubin

et al. 2011

Tissue Engineering Part A

273

290

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Poly(ethylene glycol) (PEG) hydrogels are popular for cell culture and tissue-engineering applications because they are nontoxic and exhibit favorable hydration and nutrient transport properties. However, cells cannot adhere to, remodel, proliferate within, or degrade PEG hydrogels. Methacrylated gelatin (GelMA), derived from denatured collagen, yields an enzymatically degradable, photocrosslinkable hydrogel that cells can degrade, adhere to and spread within. To combine the desirable features of each of these materials we synthesized PEGGelMA composite hydrogels, hypothesizing that copolymerization would enable adjustable cell binding, mechanical, and degradation properties. The addition of GelMA to PEG resulted in a composite hydrogel that exhibited tunable mechanical and biological profiles. Adding GelMA (5%-15% w/v) to PEG (5% and 10% w/v) proportionally increased fibroblast surface binding and spreading as compared to PEG hydrogels ( p < 0.05). Encapsulated fibroblasts were also able to form 3D cellular networks 7 days after photoencapsulation only within composite hydrogels as compared to PEG alone. Additionally, PEG-GelMA hydrogels displayed tunable enzymatic degradation and stiffness profiles. PEG-GelMA composite hydrogels show great promise as tunable, cell-responsive hydrogels for 3D cell culture and regenerative medicine applications.

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The pro-angiogenic characteristics of a cross-linked gelatin matrix

Cited by 90 publications

References 39 publications

Effect of Locally Applied Fluvastatin in Low-turnover Osteoporosis Model Mouse with Femur Bone Defect

Effect of Locally Applied Fluvastatin in Low-turnover Osteoporosis Model Mouse with Femur Bone Defect

Bio-ink properties and printability for extrusion printing living cells

Synthesis and Characterization of Tunable Poly(Ethylene Glycol): Gelatin Methacrylate Composite Hydrogels

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