Biofabrication of SDF-1 Functionalized 3D-Printed Cell-Free Scaffolds for Bone Tissue Regeneration

Lauer, Alina; Wolf, Philipp; Mehler, Dorothea; Götz, Hermann; Rüzgar, Mehmet; Baranowski, Andreas; Henrich, Dirk; Rommens, Pol Maria; Ritz, Ulrike

doi:10.3390/ijms21062175

Cited by 22 publications

(23 citation statements)

References 61 publications

(68 reference statements)

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“…To analyze degradation, longer-lasting animal studies are necessary. The transplantation of a similarly dimensioned, 3D-printed, porous tube structure into a plate-stabilized 5 mm defect in the rat femur by two authors of this study showed signs of degradation of the implanted PLA scaffold after eight weeks of healing time [47]. It is concluded that, for a sufficient analysis of the degradation, a standing time of at least six months is necessary.…”

Section: Scaffold Design Mechanics and Biological Aspectsmentioning

confidence: 62%

“…The individual hollow column subunit thus offers all biologically relevant features and could be tested individually in the established small animal model, in the future [43][44][45][46]. Transplantation of a similarly dimensioned, 3D-printed, porous hollow column structure into a plate-stabilized 5 mm defect in the rat femur by two authors of this study showed promising healing results [47]. Transfer to a large animal model is conceivable, since current data indicate that scaffolds based on 3D printed fused filament fabrication can be effective for the treatment of large bone defects in large animals [9,[48][49][50].…”

Section: Process Developmentmentioning

confidence: 89%

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3D-Printing of Hierarchically Designed and Osteoconductive Bone Tissue Engineering Scaffolds

et al. 2020

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In Bone Tissue Engineering (BTE), autologous bone-regenerative cells are combined with a scaffold for large bone defect treatment (LBDT). Microporous, polylactic acid (PLA) scaffolds showed good healing results in small animals. However, transfer to large animal models is not easily achieved simply by upscaling the design. Increasing diffusion distances have a negative impact on cell survival and nutrition supply, leading to cell death and ultimately implant failure. Here, a novel scaffold architecture was designed to meet all requirements for an advanced bone substitute. Biofunctional, porous subunits in a load-bearing, compression-resistant frame structure characterize this approach. An open, macro- and microporous internal architecture (100 µm–2 mm pores) optimizes conditions for oxygen and nutrient supply to the implant’s inner areas by diffusion. A prototype was 3D-printed applying Fused Filament Fabrication using PLA. After incubation with Saos-2 (Sarcoma osteogenic) cells for 14 days, cell morphology, cell distribution, cell survival (fluorescence microscopy and LDH-based cytotoxicity assay), metabolic activity (MTT test), and osteogenic gene expression were determined. The adherent cells showed colonization properties, proliferation potential, and osteogenic differentiation. The innovative design, with its porous structure, is a promising matrix for cell settlement and proliferation. The modular design allows easy upscaling and offers a solution for LBDT.

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Section: Scaffold Design Mechanics and Biological Aspectsmentioning

confidence: 62%

Section: Process Developmentmentioning

confidence: 89%

3D-Printing of Hierarchically Designed and Osteoconductive Bone Tissue Engineering Scaffolds

et al. 2020

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“…We and others combined PLA and collagen to take advantage of the different properties of these materials: The mechanical stability of polylactide, although lower than bone, is still high enough to be used as bone substitute[ 26 ], and the soft material collagen, which can be modified with various bioactive molecules[ 18 ]. We and others printed PLA together with collagen to induce tissue regeneration in different bone defects[ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Bone Sialoprotein Immobilized in Collagen Type I Enhances Bone Regeneration In vitro and In vivo

Kriegel¹,

Schlösser²,

Habeck³

et al. 2022

IJB

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The use of bioactive molecules is a promising approach to enhance the bone healing properties of biomaterials. The aim of this study was to define the role of bone sialoprotein (BSP) immobilized in collagen type I in various settings. In vitro studies with human primary osteoblasts in mono- or in co-culture with endothelial cells demonstrated a slightly increased gene expression of osteogenic markers as well as an increased proliferation rate in osteoblasts after application of BSP immobilized in collagen type I. Two critical size bone defect models were used to analyze bone regeneration. BSP incorporated in collagen type I increased bone regeneration only marginally at one concentration in a calvarial defect model. To induce the mechanical stability, three-dimensional printing was used to produce a stable porous cylinder of polylactide. The cylinder was filled with collagen type I and immobilized BSP and implanted into a femoral defect of critical size in rats. This hybrid material was able to significantly induce bone regeneration. Our study clearly shows the osteogenic effect of BSP when combined with collagen type I as carrier and thereby offers various approaches and options for its use as bioactive molecule in bone substitute materials.

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“…Lauer et al developed a 3D-printed polylactide (PLA) cylinder and functionalized it with SDF-1 for use in a rat femur bone defect. They found that the addition of SDF-1 resulted in osteoinductive effects [ 47 ]. In our study, the Gel/HA–HAP–SDF-1 composite we made showed similar results.…”

Section: Discussionmentioning

confidence: 99%

Fabrication of Stromal Cell-Derived Factor-1 Contained in Gelatin/Hyaluronate Copolymer Mixed with Hydroxyapatite for Use in Traumatic Bone Defects

et al. 2021

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Bone defects of orthopedic trauma remain a challenge in clinical practice. Regarding bone void fillers, besides the well-known osteoconductivity of most bone substitutes, osteoinductivity has also been gaining attention in recent years. It is known that stromal cell-derived factor-1 (SDF-1) can recruit mesenchymal stem cells (MSCs) in certain circumstances, which may also play an important role in bone regeneration. In this study, we fabricated a gelatin/hyaluronate (Gel/HA) copolymer mixed with hydroxyapatite (HAP) and SDF-1 to try and enhance bone regeneration in a bone defect model. After material characterization, these Gel/HA–HAP and Gel/HA–HAP–SDF-1 composites were tested for their biocompatibility and ability to recruit MSCs in vitro. A femoral condyle bone defect model of rats was used for in vivo studies. For the assessment of bone healing, micro-CT analysis, second harmonic generation (SHG) imaging, and histology studies were performed. As a result, the Gel/HA–HAP composites showed no systemic toxicity to rats. Gel/HA–HAP composite groups both showed better bone generation compared with the control group in an animal study, and the composite with the SDF-1 group even showed a trend of faster bone growth compared with the composite without SDF-1 group. In conclusion, in the management of traumatic bone defects, Gel/HA–HAP–SDF-1 composites can be a feasible material for use as bone void fillers.

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Biofabrication of SDF-1 Functionalized 3D-Printed Cell-Free Scaffolds for Bone Tissue Regeneration

Cited by 22 publications

References 61 publications

3D-Printing of Hierarchically Designed and Osteoconductive Bone Tissue Engineering Scaffolds

3D-Printing of Hierarchically Designed and Osteoconductive Bone Tissue Engineering Scaffolds

Bone Sialoprotein Immobilized in Collagen Type I Enhances Bone Regeneration In vitro and In vivo

Fabrication of Stromal Cell-Derived Factor-1 Contained in Gelatin/Hyaluronate Copolymer Mixed with Hydroxyapatite for Use in Traumatic Bone Defects

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