Development of mussel-inspired 3D-printed poly (lactic acid) scaffold grafted with bone morphogenetic protein-2 for stimulating osteogenesis

Cheng, Cheng-Hsin; Chen, Yiwen; Lee, Alvin Kai-Xing; Yao, Chun‐Hsu; Shie, Ming‐You

doi:10.1007/s10856-019-6279-x

Cited by 36 publications

(40 citation statements)

References 51 publications

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“…28 The particle packing and construct densification cause not only the decreasing porosity but also the increasing tortuosity of the inner pore structure in the rod. The effect of varying tortuosity on release profile of the protein from construct was derived from equation (6) and plotted in Figure 7(b). The interstices in the polymer rod matrix are filled with aqueous hydrogel, which is both the carrier and transport medium for the proteins in hybrid suspension based construct.…”

Section: D Printability Of the Hybrid Suspensionmentioning

confidence: 99%

“…Though 3 D printing technology have seen success in manufacture of solid dosage forms for small pharmaceutical molecules, 3d printed protein delivery system has to face many difficult challenges. 6,7 Many 3 D printing technologies, such as most extensively researched fused deposition modeling, might not be suitable for protein that are thermolabile and sensitive to many chemical excipients. In addition, most available materials capable of protein delivery are either mechanically weak or lack the desirable rheological properties for good control of the structure and good reproducibility for 3 D printing.…”

Section: Introductionmentioning

confidence: 99%

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3D-printed construct from hybrid suspension as spatially and temporally controlled protein delivery system

et al. 2021

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Protein delivery systems have been extensively applied in controlled releasing of protein or polypeptides for therapeutic treatment or tissue regeneration. While 3 D printing technology shows great promise in novel dosage form with tailoring dose size and drug release profile, 3 D printable protein delivery system has to face many difficult challenges. In this study, we developed a hybrid suspension combining Eudragit polyacrylate colloid as matrix material and Pluronic polyether hydrogel as diffusion channel for protein release. This hybrid suspension can be 3 D-printed into construct with complex shape and inner structures thanks to its pseudoplastic and thixotropic rheological properties. The protein can be incorporated in hybrid suspension either in its original or nanoparticle capsulated form. The experiment shows that the protein release from construct is a function of drying time, molecular weight (MW) of chitosan, as well as their own structural/diffusional properties. Also, the theoretical derivation suggests polyacrylate matrix tortuosity, chitosan erosion rate as well as hydrogel diffusion coefficient all contributed to the extended duration of release profile. In addition, cytotoxicity test through cell culture confirmed that the construct fabricated from hybrid suspension exhibit relative good bio-compatibility. Finally, heterogeneous constructs with zoned design were fabricated as protein delivery system, which demonstrated the capability of hybrid suspension technique for spatial and temporal release of macromolecular drugs to realize pharmaceutical effectiveness or guild cell organization.

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Section: D Printability Of the Hybrid Suspensionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

3D-printed construct from hybrid suspension as spatially and temporally controlled protein delivery system

et al. 2021

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“…The optical density of alizarin red S was quantified through the ELISA assay and the quantification results were in good agreement with the results presented above. It was reported that a vascularized scaffold with VEGF had an additive effect on cellular differentiation and proliferation as compared with neat bioceramics materials [53]. Therefore, it is important to verify whether the VEGF-loaded scaffold can accelerate bone tissue regeneration in vivo.…”

Section: Osteogenesismentioning

confidence: 99%

Assessment of the Release of Vascular Endothelial Growth Factor from 3D-Printed Poly-ε-Caprolactone/Hydroxyapatite/Calcium Sulfate Scaffold with Enhanced Osteogenic Capacity

Chen

Wang

et al. 2020

Polymers

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Vascular endothelial growth factor (VEGF) is one of the most crucial growth factors and an assistant for the adjustment of bone regeneration. In this study, a 3D scaffold is fabricated using the method of fused deposition modeling. Such a fabricated method allows us to fabricate scaffolds with consistent pore sizes, which could promote cellular ingrowth into scaffolds. Therefore, we drafted a plan to accelerate bone regeneration via VEGF released from the hydroxyapatite/calcium sulfate (HACS) scaffold. Herein, HACS will gradually degrade and provide a suitable environment for cell growth and differentiation. In addition, HACS scaffolds have higher mechanical properties and drug release compared with HA scaffolds. The drug release profile of the VEGF-loaded scaffolds showed that VEGF could be loaded and released in a stable manner. Furthermore, initial results showed that VEGF-loaded scaffolds could significantly enhance the proliferation of human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVEC). In addition, angiogenic- and osteogenic-related proteins were substantially increased in the HACS/VEGF group. Moreover, in vivo results revealed that HACS/VEGF improved the regeneration of the rabbit’s femur bone defect, and VEGF loading improved bone tissue regeneration and remineralization after implantation for 8 weeks. All these results strongly imply that the strategy of VEGF loading onto scaffolds could be a potential candidate for future bone tissue engineering.

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“…3D printing is another emerging technique to generate anatomically-shaped scaffolds [13][14][15][16][17][18]. Fused deposition modeling (FDM) is the most widely used 3D printing technique in tissue engineering [19][20][21][22]. Even though there are many commercially available FDM 3D printers on the market, these printers only print solid polymers such as polylactic acid polymer (PLA) and polycaprolactone (PCL).…”

mentioning

confidence: 99%

Rapid Fabrication of Anatomically-Shaped Bone Scaffolds Using Indirect 3D Printing and Perfusion Techniques

Grottkau

Hui

Yao

et al. 2020

IJMS

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Fused deposit modeling (FDM) 3D printing technology cannot generate scaffolds with high porosity while maintaining good integrity, anatomical-surface detail, or high surface area-to-volume ratio (S/V). Solvent casting and particulate leaching (SCPL) technique generates scaffolds with high porosity and high S/V. However, it is challenging to generate complex-shaped scaffolds; and solvent, particle and residual water removal are time consuming. Here we report techniques surmounting these problems, successfully generating a highly porous scaffold with the anatomical-shape characteristics of a human femur by polylactic acid polymer (PLA) and PLA-hydroxyapatite (HA) casting and salt leaching. The mold is water soluble and is easily removable. By perfusing with ethanol, water, and dry air sequentially, the solvent, salt, and residual water were removed 20 fold faster than utilizing conventional methods. The porosities are uniform throughout the femoral shaped scaffold generated with PLA or PLA-HA. Both scaffolds demonstrated good biocompatibility with the pre-osteoblasts (MC3T3-E1) fully attaching to the scaffold within 8 h. The cells demonstrated high viability and proliferation throughout the entire time course. The HA-incorporated scaffolds demonstrated significantly higher compressive strength, modulus and osteoinductivity as evidenced by higher levels of alkaline-phosphatase activity and calcium deposition. When 3D printing a 3D model at 95% porosity or above, our technology preserves integrity and surface detail when compared with FDM-generated scaffolds. Our technology can also generate scaffolds with a 31 fold larger S/V than FDM. We have developed a technology that is a versatile tool in creating personalized, patient-specific bone graft scaffolds efficiently with high porosity, good scaffold integrity, high anatomical-shaped surface detail and large S/V.

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Development of mussel-inspired 3D-printed poly (lactic acid) scaffold grafted with bone morphogenetic protein-2 for stimulating osteogenesis

Cited by 36 publications

References 51 publications

3D-printed construct from hybrid suspension as spatially and temporally controlled protein delivery system

3D-printed construct from hybrid suspension as spatially and temporally controlled protein delivery system

Assessment of the Release of Vascular Endothelial Growth Factor from 3D-Printed Poly-ε-Caprolactone/Hydroxyapatite/Calcium Sulfate Scaffold with Enhanced Osteogenic Capacity

Rapid Fabrication of Anatomically-Shaped Bone Scaffolds Using Indirect 3D Printing and Perfusion Techniques

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