Synthesis and characterization of a novel injectable alginate–collagen–hydroxyapatite hydrogel for bone tissue regeneration

Bendtsen, Stephanie T.; Wei, Mei

doi:10.1039/c5tb00072f

Cited by 94 publications

(54 citation statements)

References 43 publications

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“…Based on our previous results, [11][12][13][14][15] PC was prepared as an injectable in vivo-forming hydrogel (Scheme 1). hDPSCs were easily mixed with PBS solution of 20 wt% PC.…”

Section: Characterization Of Hdpscs-loaded Pc Solutionsmentioning

confidence: 99%

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In Vivo Osteogenic Differentiation of Human Dental Pulp Stem Cells Embedded in an Injectable In Vivo‐Forming Hydrogel

Jang

Park

et al. 2016

Macromolecular Bioscience

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In this study, human dental pulp stem cells (hDPSCs) are examined as a cellular source for bone tissue engineering using an in vivo-forming hydrogel. The hDPSCs are easily harvested in large quantities from extracted teeth. The stemness of harvested hDPSCs indicates their relative tolerance to ex vivo manipulation in culture. The in vitro osteogenic differentiation of hDPSCs is characterized using Alizarin Red S (ARS), von Kossa (VK), and alkaline phosphatase (ALP) staining. The solution of hDPSCs and a methoxy polyethylene glycol-polycaprolactone block copolymer (PC) is easily prepared by simple mixing at room temperature and in no more than 10 s it forms in vivo hydrogels after subcutaneous injection into rats. In vivo osteogenic differentiation of hDPSCs in the in vivo-forming hydrogel is confirmed by micro-computed tomography (CT), histological staining, and gene expression. Micro-CT analysis shows evidence of significant tissue-engineered bone formation in hDPSCs-loaded hydrogel in the presence of osteogenic factors. Differentiated osteoblasts in in vivo-forming hydrogel are identified by ARS and VK staining and are found to exhibit characteristic expression of genes like osteonectin, osteopontin, and osteocalcin. In conclusion, hDPSCs embedded in an in vivo-forming hydrogel may provide benefits as a noninvasive formulation for bone tissue engineering applications.

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“…Based on our previous results, [11][12][13][14][15] PC was prepared as an injectable in vivo-forming hydrogel (Scheme 1). hDPSCs were easily mixed with PBS solution of 20 wt% PC.…”

Section: Characterization Of Hdpscs-loaded Pc Solutionsmentioning

confidence: 99%

“…[10][11][12][13][14][15][16][17][18] Among them, PCL is an attractive biodegradable polyester due to its biodegradability and good biocompatibility. Because PCL has a slower rate of degradation than PLLA, PGA, and PLGA, it can be a longer biodegradable biomaterial in vivo.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Osteogenic Differentiation of Human Dental Pulp Stem Cells Embedded in an Injectable In Vivo‐Forming Hydrogel

Jang

Park

et al. 2016

Macromolecular Bioscience

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“…The optimal formulations will also be suitable to print larger, more complex designs, which will be investigated in future studies. As an injectable alginate hydrogel formulation with a gelation time defined as optimal in a surgical setting has been developed in our laboratory, it was hypothesized that a hydrogel optimal for 3D printing could be developed as well . Thus, formulation 1 was adapted from our previous studies due to its optimal injectability.…”

Section: Discussionmentioning

confidence: 99%

“…As an injectable alginate hydrogel formulation with a gelation time defined as optimal in a surgical setting has been developed in our laboratory, it was hypothesized that a hydrogel optimal for 3D printing could be developed as well. 37 Thus, formulation 1 was adapted from our previous studies due to its optimal injectability. This composition served as a baseline formulation on which we modified, based on our knowledge of alginate's gelation mechanism, to develop an ideal formulation for 3D printing.…”

Section: Hydrogel Printabilitymentioning

confidence: 99%

Development of a novel alginate‐polyvinyl alcohol‐hydroxyapatite hydrogel for 3D bioprinting bone tissue engineered scaffolds

Bendtsen

Quinnell

Wei

2017

J Biomedical Materials Res

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278

189

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Three-dimensional printed biomaterials used as personalized tissue substitutes have the ability to promote and enhance regeneration in areas of defected tissue. The challenge with 3D printing for bone tissue engineering remains the selection of a material with optimal rheological properties for printing in addition to biocompatibility and capacity for uniform cell incorporation. Hydrogel biomaterials may provide sufficient printability to allow cell encapsulation and bioprinting of scaffolds with uniform cell distribution. In this study, a novel alginate-polyvinyl alcohol (PVA)-hydroxyapatite (HA) hydrogel formulation with optimal rheological properties for 3D bioprinting of mouse calvaria 3T3-E1 (MC3T3) cells into scaffolds of high shape fidelity has been developed. A systematic investigation was conducted to determine the effect of varying concentrations of alginate, phosphate, calcium, and the PVA-HA suspension in the formulation on the resulting viscosity and thus printability of the hydrogel. HA, the main mineral component in natural bone, was incorporated into the hydrogel formulation to create a favorable bone-forming environment due to its excellent osteoconductivity. Degradation studies in α-MEM cell culture media showed that the 3D printed alginate-PVA-HA scaffolds remained in-tact for 14 days. MC3T3 cells were well distributed and encapsulated throughout the optimal hydrogel formulation and expressed high viability through the completion of the 3D printing process. Thus, the development of this novel, osteoconductive, biodegradable, alginate-PVA-HA formulation and its ability to 3D bioprint tissue engineered scaffolds make it a promising candidate for treating personalized bone defects. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1457-1468, 2017.

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“…For each scaffold type, scaffolds incubated in 0.5% (w/v) CaCl 2 baths showed a greater release than those incubated in 1.0% (w/v) CaCl 2 baths. This can be attributed to the fact that the lower calcium concentration results in a lower degree of crosslinking and thus lower mechanical properties of the scaffolds . Thus, the weaker scaffolds are prone to a greater degree of media intake and swelling, leading to increased diffusion of the FITC‐dextran out of the matrix and into the surrounding media .…”

Section: Discussionmentioning

confidence: 99%

In vitro evaluation of 3D bioprinted tri‐polymer network scaffolds for bone tissue regeneration

Bendtsen

Wei

2017

J Biomedical Materials Res

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In vitro evaluations provide vital information on the ability of tissue engineered scaffolds to support cell life and promote natural physiological behaviors in culture. Such assessments are necessary to conduct before implementation of the scaffolds for tissue healing in vivo. The scaffold extracellular matrix must provide the biochemical and mechanical cues necessary to promote cellular attachment, migration and proliferation before differentiation and new tissue deposition can occur. In this study, an in vitro evaluation was conducted to assess the ability of scaffolds three-dimensional (3D) printed with a previously developed alginate-polyvinyl alcohol-hydroxyapatite formulation to promote proliferation of encapsulated MC3T3 cells. A systematic investigation was conducted to increase cell proliferation, and it was determined that the concentration and duration of the calcium bath have a less effect on proliferation than the composition of the formulation itself. Collagen gel was incorporated into the formulation to provide cells with adhesion sites necessary to sufficiently attach to the matrix. Enhanced proliferation was achieved within scaffolds of increased collagen content and sufficient crosslinking. This highlighted the importance of the synergistic effect created as a result of sufficient ligand density coupled with appropriate scaffold mechanical rigidity to provide a suitable environment for proliferation. Thus, these 3D printed tri-polymer scaffolds have the ability to support cell proliferation and have potential to promote cell differentiation and new bone tissue deposition. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3262-3272, 2017.

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Synthesis and characterization of a novel injectable alginate–collagen–hydroxyapatite hydrogel for bone tissue regeneration

Abstract: This novel fabrication process allowed for the development of an injectable hydrogel system with a gelation time suitable for a surgical setting and components necessary for promoting enhanced bone regeneration.

Cited by 94 publications

References 43 publications

In Vivo Osteogenic Differentiation of Human Dental Pulp Stem Cells Embedded in an Injectable In Vivo‐Forming Hydrogel

In Vivo Osteogenic Differentiation of Human Dental Pulp Stem Cells Embedded in an Injectable In Vivo‐Forming Hydrogel

Development of a novel alginate‐polyvinyl alcohol‐hydroxyapatite hydrogel for 3D bioprinting bone tissue engineered scaffolds

In vitro evaluation of 3D bioprinted tri‐polymer network scaffolds for bone tissue regeneration

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