In vitro and in vivo Biocompatibility of Alginate Dialdehyde/Gelatin Hydrogels with and without Nanoscaled Bioactive Glass for Bone Tissue Engineering Applications

Rottensteiner, Ulrike; Sarker, Bapi; Heusinger, Dominik; Dafinova, Diana; Rath, Subha Narayan; Beier, Justus P.; Kneser, Ulrich; Horch, Raymund E.; Detsch, Rainer; Boccaccını, Aldo R.; Arkudas, Andreas

doi:10.3390/ma7031957

Cited by 117 publications

(89 citation statements)

References 50 publications

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“…Duan et al improved the physical and biological properties of bio-printed alginate hydrogel combined with gelatin [58]. Also, favorable biological properties of alginate/gelatin hydrogels for bone tissue engineering has been reported by Rottensteiner et al [59]. In fact, a number of drawbacks are known for pure alginate, including low promotion of cell adhesion and slow and uncontrolled degradation kinetics in physiological conditions [60, 61].…”

Section: Discussionmentioning

confidence: 99%

3D printed TCP-based scaffold incorporating VEGF-loaded PLGA microspheres for craniofacial tissue engineering

et al. 2017

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Vascularization is a critical process during bone regeneration/repair and the lack of tissue vascularization is recognized as a major challenge in applying bone tissue engineering methods for cranial and maxillofacial surgeries. The aim of our study is to fabricate a vascular endothelial growth factor (VEGF)-loaded gelatin/alginate/β-TCP composite scaffold by 3D printing method using a computer-assisted design (CAD) model. Rheological characterization of various gelatin/alginate/β-TCP formulations led to an optimized paste as a printable bioink at room temperature. VEGF-loaded PLGA microspheres were then incorporated into the paste prior to printing to ensure sustained release of the growth factor. The in vitro release kinetics of the loaded VEGF revealed that the designed scaffolds fulfill the bioavailability of VEGF required for vascularization in the early stages of tissue regeneration. The results were confirmed by two times increment of proliferation of human umbilical vein endothelial cells (HUVECs) seeded on the scaffolds after 10 days. The compressive modulus of the scaffolds, 98 ± 11 MPa, was found to be in the range of cancellous bone suggesting their potential application for craniofacial tissue engineering. Osteoblast culture on the scaffolds showed that the construct supports cell viability, adhesion and proliferation. It was found that the ALP activity increased over 50% using VEGF-loaded scaffolds after 2 weeks of culture. In conclusion, the 3D printed gelatin/alginate/β-TCP scaffold with slow releasing of VEGF can be considered as a potential candidate for regeneration of craniofacial defects.

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Section: Discussionmentioning

confidence: 99%

3D printed TCP-based scaffold incorporating VEGF-loaded PLGA microspheres for craniofacial tissue engineering

et al. 2017

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“…Gelatin hydrogels were chosen for this study because gelatin is a commonly used enzymatically degradable naturally-derived polymer [63, 64], and because the properties of gelatin hydrogels, including crosslinking density and degradation profile, can be easily controlled via chemical crosslinking with glutaraldehyde [29, 65, 66]. However, increasing crosslinking also increases mechanical properties and decreases degradability, obscuring interpretation of the effects of these properties on the foreign body response.…”

Section: Discussionmentioning

confidence: 99%

Temporal and spatial distribution of macrophage phenotype markers in the foreign body response to glutaraldehyde-crosslinked gelatin hydrogels

Wang

Nassiri

et al. 2016

Journal of Biomaterials Science, Polymer Edition

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In recent years, macrophage phenotype has emerged as an important determinant of the success or failure of implanted polymeric biomaterials. However, it is not well understood how changes in biomaterials properties affect the foreign body response or macrophage behavior. Because failed attempts at biomaterial degradation by macrophages have been linked to frustrated phagocytosis, a defining feature of the foreign body response, we hypothesized that increased hydrogel crosslinking density (and decreased degradability) would exacerbate the foreign body response. Gelatin hydrogels were crosslinked with glutaraldehyde (0.05%, 0.1%, and 0.3%) and implanted subcutaneously in C57BL/6 mice over the course of 3 weeks. Histological and immunohistochemical analysis was used to characterize fibrous capsule formation and the temporal and spatial distribution of macrophage phenotype markers. Interestingly, changes in hydrogel crosslinking did not affect the thickness of the fibrous capsule surrounding the hydrogels, expression of the pan-macrophage marker F480, expression of three macrophage phenotype markers (iNOS, Arg1, CD163), or expression of the myofibroblast marker aSMA. With respect to temporal changes, the level of expression of the M1 marker (iNOS) remained relatively constant throughout the study, while the M2 markers Arg1 and CD163 increased over time. Expression of these M2 markers was highly correlated with fibrous capsule thickness. Differences in spatial distribution of staining also were noted, with the strongest staining for iNOS at the hydrogel surface and increasing expression of the myofibroblast marker aSMA toward the outer edge of the fibrous capsule. These results confirm previous reports that macrophages in the foreign body response exhibit characteristics of both M1 and M2 phenotypes. Understanding the effects (or lack of effects) of biomaterial properties on the foreign body response and macrophage phenotype may aid in the rational design of biomaterials to integrate with surrounding tissue.

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“…Bioactive glasses are important biomaterials for bone tissue regeneration due to their bioactivity and osteoconductivity [15,16,27]. Since the discovery of 45S5 BG in 1971 there have been over one million patients who have received this bone substitute for surgery [15,28] Rottensteiner et al [31]. Beside pastes and putties use, these hybrid systems are also promising approaches for additive manufacturing of biomedical implants and even for biofabrication [32,33].…”

Section: Discussionmentioning

confidence: 99%

Nanoscale Bioactive Glass Activates Osteoclastic Differentiation of RAW 264.7 Cells

Detsch

Rübner

Strissel

et al. 2016

Nanomedicine (Lond.)

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(215 words)Key words: osteoclasts; biomaterials; 45S5 nanoscaled (n) Bioactive glass (BG) 2 AbstractPresently, there is limited knowledge regarding the differentiation of osteoclasts in the presence of nanoscale bioactive glasses (nBG). This investigation examined increasing concentrations of 45S5 nBG and its influence on osteoclast differentiation. After 14 days of culturing cells with 500 µg/ml nBG viability of ~100% was detected, however DNA synthesis was reduced supporting the differentiation into osteoclast-like cells. RNA activation of nine genes occurred in a nBG concentration dependent manner. Low concentrations of nBG increased expression of genes involved in commitment to cell fusion. High concentration of nBG increased gene expression supporting osteoclast-like differentiation. We conclude that nBG enhances RAW 264.7 osteoclast differentiation especially controlling gene expression in a concentration dependent manner, which could reflect normal regulation during bone growth.Background: There is limited knowledge regarding differentiation of osteoclasts in the presence of nanoscale bioactive glasses (nBG). This investigation examined increasing concentrations of 45S5 nBG and its influence on osteoclast differentiation. Materials and Methods:Different concentrations of 45S5 nBG were cultured up to 14 days with the murine RAW264.7 cell line and human primary monocytes and M-CSF and RANKL.

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In vitro and in vivo Biocompatibility of Alginate Dialdehyde/Gelatin Hydrogels with and without Nanoscaled Bioactive Glass for Bone Tissue Engineering Applications

Cited by 117 publications

References 50 publications

3D printed TCP-based scaffold incorporating VEGF-loaded PLGA microspheres for craniofacial tissue engineering

3D printed TCP-based scaffold incorporating VEGF-loaded PLGA microspheres for craniofacial tissue engineering

Temporal and spatial distribution of macrophage phenotype markers in the foreign body response to glutaraldehyde-crosslinked gelatin hydrogels

Nanoscale Bioactive Glass Activates Osteoclastic Differentiation of RAW 264.7 Cells

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