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  • 1
    Online Resource
    Online Resource
    Treatment of Critical-Size Femoral Bone Defects with Chitosan Scaffolds Produced by a Novel Process from Textile Engineering
    MDPI AG ; 2021
    In:  Biomedicines Vol. 9, No. 8 ( 2021-08-14), p. 1015-
    Details
    In: Biomedicines, MDPI AG, Vol. 9, No. 8 ( 2021-08-14), p. 1015-
    Abstract: The purpose of this study was to investigate, in vitro and in vivo, the suitability of chitosan (CHS) scaffolds produced by the net-shape-nonwoven (NSN) technology, for use as bone graft substitutes in a critical-size femoral bone defect in rats. For in vitro investigations, scaffolds made of CHS, mineralized collagen (MCM), or human cancellous bone allograft (CBA) were seeded with human telomerase-immortalized mesenchymal stromal cells (hTERT-MSC), incubated for 14 days, and thereafter evaluated for proliferation and osteogenic differentiation. In vivo, CHS, MCM and CBA scaffolds were implanted into 5 mm critical-size femoral bone defects in rats. After 12 weeks, the volume of newly formed bone was determined by microcomputed tomography (µCT), while the degree of defect healing, as well as vascularization and the number of osteoblasts and osteoclasts, was evaluated histologically. In vitro, CHS scaffolds showed significantly higher osteogenic properties, whereas treatment with CHS, in vivo, led to a lower grade of bone-healing compared to CBA and MCM. While chitosan offers a completely new field of scaffold production by fibers, these scaffolds will have to be improved in the future, regarding mechanical stability and osteoconductivity.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines9081015
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720867-9
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  • 2
    Online Resource
    Online Resource
    Cell spheroids are as effective as single cells suspensions in the treatment of critical-sized bone defects
    Springer Science and Business Media LLC ; 2021
    In:  BMC Musculoskeletal Disorders Vol. 22, No. 1 ( 2021-12)
    Details
    In: BMC Musculoskeletal Disorders, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2021-12)
    Abstract: Due to their multilineage potential and high proliferation rate, mesenchymal stem cells (MSC) indicate a sufficient alternative in regenerative medicine. In comparison to the commonly used 2-dimensional culturing method, culturing cells as spheroids stimulates the cell-cell communication and mimics the in vivo milieu more accurately, resulting in an enhanced regenerative potential. To investigate the osteoregenerative potential of MSC spheroids in comparison to MSC suspensions, cell-loaded fibrin gels were implanted into murine critical-sized femoral bone defects. Methods After harvesting MSCs from 4 healthy human donors and preculturing and immobilizing them in fibrin gel, cells were implanted into 2 mm murine femoral defects and stabilized with an external fixator. Therefore, 26 14- to 15-week-old nu/nu NOD/SCID nude mice were randomized into 2 groups (MSC spheroids, MSC suspensions) and observed for 6 weeks. Subsequently, micro-computed tomography scans were performed to analyze regenerated bone volume and bone mineral density. Additionally, histological analysis, evaluating the number of osteoblasts, osteoclasts and vessels at the defect side, were performed. Statistical analyzation was performed by using the Student’s t-test and, the Mann-Whitney test. The level of significance was set at p  = 0.05. Results μCT-analysis revealed a significantly higher bone mineral density of the MSC spheroid group compared to the MSC suspension group. However, regenerated bone volume of the defect side was comparable between both groups. Furthermore, no significant differences in histological analysis between both groups could be shown. Conclusion Our in vivo results reveal that the osteo-regenerative potential of MSC spheroids is similar to MSC suspensions.
    Type of Medium: Online Resource
    ISSN: 1471-2474
    URL: Article
    DOI: 10.1186/s12891-021-04264-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041355-5
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  • 3
    Online Resource
    Online Resource
    Effectiveness of Dental Pulp-derived Stem Cells and Bone Marrowderived Mesenchymal Stromal Cells Implanted into a Murine Critical Bone Defect
    Bentham Science Publishers Ltd. ; 2022
    In:  Current Stem Cell Research & Therapy Vol. 17, No. 5 ( 2022-07), p. 480-491
    Details
    In: Current Stem Cell Research & Therapy, Bentham Science Publishers Ltd., Vol. 17, No. 5 ( 2022-07), p. 480-491
    Abstract: While bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been used for many years in bone tissue engineering applications, the procedure still has drawbacks such as painful collection methods and damage to the donor site. Dental pulp-derived stem cells (DPSCs) are readily accessible, occur in high amounts, and show a high proliferation and differentiation capability. Therefore, DPSCs may be a promising alternative for BM-MSCs to repair bone defects. Objective: The aim of this study was to investigate the bone regenerative potential of DPSCs in comparison to BM-MSCs in vitro and in vivo. Methods: In vitro investigations included analysis of cell doubling time as well as proliferation and osteogenic differentiation. For the in vivo study, 36 male NMRI nude mice were randomized into 3 groups: 1) control (cell-free mineralized collagen matrix (MCM) scaffold), 2) MCM + DPSCs, and 3) MCM + BMMSCs. Critical size 2 mm bone defects were created at the right femur of each mouse and stabilized by an external fixator. After 6 weeks, animals were euthanized, and microcomputed tomography scans (μCT) and histological analyses were performed. Results: In vitro DPSCs showed a 2-fold lower population doubling time and a 9-fold higher increase in proliferation when seeded onto MCM scaffolds as compared to BM-MSCs, but DPSCs showed a significantly lower osteogenic capability than BM-MSCs. In vivo, the healing of the critical bone defect in NMRI nude mice was comparable among all groups. Conclusions: Pre-seeding of MCM scaffolds with DPSCs and BM-MSCs did not enhance bone defect healing.
    Type of Medium: Online Resource
    ISSN: 1574-888X
    URL: Article
    DOI: 10.2174/1574888X17666220215100732
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2022
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  • 4
    Online Resource
    Online Resource
    Two‐step stem cell therapy improves bone regeneration compared to concentrated bone marrow therapy
    Wiley ; 2019
    In:  Journal of Orthopaedic Research Vol. 37, No. 6 ( 2019-06), p. 1318-1328
    Details
    In: Journal of Orthopaedic Research, Wiley, Vol. 37, No. 6 ( 2019-06), p. 1318-1328
    Abstract: Adult stem cells are a promising tool to positively influence bone regeneration. Concentrated bone marrow therapy entails isolating osteoprogenitor cells during surgery with, however, only low cells yield. Two step stem cell therapy requires an additional harvesting procedure but generates high numbers of progenitor cells that facilitate osteogenic pre‐differentiation. To further improve bone regeneration, stem cell therapy can be combined with growth factors from platelet rich plasma (PRP) or its lysate (PL) to potentially fostering vascularization. The aim of this study was to investigate the effects of bone marrow concentrate (BMC), osteogenic pre‐differentiation of mesenchymal stromal cells (MSCs), and PL on bone regeneration and vascularization. Bone marrow from four different healthy human donors was used for either generation of BMC or for isolation of MSCs. Seventy‐two mice were randomized to six groups (Control, PL, BMC, BMC + PL, pre‐differentiated MSCs, pre‐differentiated MSCs + PL). The influence of PL, BMC, and pre‐differentiated MSCs was investigated systematically in a 2 mm femoral bone defect model. After a 6‐week follow‐up, the pre‐differentiated MSCs + PL group showed the highest bone volume, highest grade of histological defect healing and highest number of bridged defects with measurable biomechanical stiffness. Using expanded and osteogenically pre‐differentiated MSCs for treatment of a critical‐size bone defect was favorable with regards to bone regeneration compared to treatment with cells from BMC. The addition of PL alone had no significant influence; therefore the role of PL for bone regeneration remains unclear. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1318–1328, 2019.
    Type of Medium: Online Resource
    ISSN: 0736-0266 , 1554-527X
    URL: Issue
    URL: Article
    DOI: 10.1002/jorr.v37.6
    DOI: 10.1002/jor.24215
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2050452-4
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  • 5
    Online Resource
    Online Resource
    A facile one-stage treatment of critical bone defects using a calcium sulfate/hydroxyapatite biomaterial providing spatiotemporal delivery of bone morphogenic protein–2 and zoledronic acid
    American Association for the Advancement of Science (AAAS) ; 2020
    In:  Science Advances Vol. 6, No. 48 ( 2020-11-27)
    Details
    In: Science Advances, American Association for the Advancement of Science (AAAS), Vol. 6, No. 48 ( 2020-11-27)
    Abstract: Bone morphogenic proteins (BMPs) are the only true osteoinductive molecules. Despite being tremendously potent, their clinical use has been limited for reasons including supraphysiological doses, suboptimal delivery systems, and the pro-osteoclast effect of BMPs. Efforts to achieve spatially controlled bone formation using BMPs are being made. We demonstrate that a carrier consisting of a powder of calcium sulfate/hydroxyapatite (CaS/HA) mixed with bone active molecules provides an efficient drug delivery platform for critical femoral defect healing in rats. The bone-active molecules were composed of osteoinductive rhBMP-2 and the bisphosphonate, and zoledronic acid (ZA) was chosen to overcome BMP-2–induced bone resorption. It was demonstrated that delivery of rhBMP-2 was necessary for critical defect healing and restoration of mechanical properties, but codelivery of BMP-2 and ZA led to denser and stronger fracture calluses. Together, the CaS/HA biomaterial with rhBMP-2 and/or ZA can potentially be used as an off-the-shelf alternative to autograft bone.
    Type of Medium: Online Resource
    ISSN: 2375-2548
    URL: Article
    DOI: 10.1126/sciadv.abc1779
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2020
    detail.hit.zdb_id: 2810933-8
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  • 6
    Online Resource
    Online Resource
    Strontium enhances BMP‐2 mediated bone regeneration in a femoral murine bone defect model
    Wiley ; 2020
    In:  Journal of Biomedical Materials Research Part B: Applied Biomaterials Vol. 108, No. 1 ( 2020-01), p. 174-182
    Details
    In: Journal of Biomedical Materials Research Part B: Applied Biomaterials, Wiley, Vol. 108, No. 1 ( 2020-01), p. 174-182
    Abstract: The application of strontium is one option for the clinical treatment of osteoporosis—a disease characterized by reduced bone density and quality—in order to reduce the risk of vertebral and nonvertebral fractures. Unlike other drugs used in osteoporosis therapy, strontium shows a dual effect on bone metabolism by attenuating cellular resorption and simultaneously enhancing new bone tissue formation. Current concerns regarding the systemic application of highly dosed strontium ranelate led to the development of strontium‐modified scaffolds based on mineralized collagen (MCM) capable to release biologically active Sr 2+ ions directly at the fracture site. In this study, we investigated the regenerative potential of these scaffolds. For in vitro investigations, human mesenchymal stromal cells were cultivated on the scaffolds for 21 days (w/ and w/o osteogenic supplements). Biochemical analysis revealed a significant promoting effect on proliferation rate and osteogenic differentiation on strontium‐modified scaffolds. In vivo, scaffolds were implanted in a murine segmental bone defect model—partly additionally functionalized with the osteogenic growth factor bone morphogenetic protein 2 (BMP‐2). After 6 weeks, bridging calluses were obtained in BMP‐2 functionalized scaffolds; the quality of the newly formed bone tissue by means of morphological scores was clearly enhanced in strontium‐modified scaffolds. Histological analysis revealed increased numbers of osteoblasts and blood vessels, decreased numbers of osteoclasts, and significantly enhanced mechanical properties. These results indicate that the combined release of Sr 2+ ions and BMP‐2 from the biomimetic scaffolds is a promising strategy to enhance bone regeneration, especially in patients suffering from osteoporosis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:174–182, 2020.
    Type of Medium: Online Resource
    ISSN: 1552-4973 , 1552-4981
    URL: Issue
    URL: Article
    DOI: 10.1002/jbm.b.v108.1
    DOI: 10.1002/jbm.b.34376
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2130917-6
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Treatment of Critical Size Femoral Bone Defects with Biomimetic Hybrid Scaffolds of 3D Plotted Calcium Phosphate Cement and Mineralized Collagen Matrix
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 6 ( 2022-03-21), p. 3400-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 6 ( 2022-03-21), p. 3400-
    Abstract: To treat critical-size bone defects, composite materials and tissue-engineered bone grafts play important roles in bone repair materials. The purpose of this study was to investigate the bone regenerative potential of hybrid scaffolds consisting of macroporous calcium phosphate cement (CPC) and microporous mineralized collagen matrix (MCM). Hybrid scaffolds were synthetized by 3D plotting CPC and then filling with MCM (MCM-CPC group) and implanted into a 5 mm critical size femoral defect in rats. Defects left empty (control group) as well as defects treated with scaffolds made of CPC only (CPC group) and MCM only (MCM group) served as controls. Eight weeks after surgery, micro-computed tomography scans and histological analysis were performed to analyze the newly formed bone, the degree of defect healing and the activity of osteoclasts. Mechanical stability was tested by 3-point-bending of the explanted femora. Compared with the other groups, more newly formed bone was found within MCM-CPC scaffolds. The new bone tissue had a clamp-like structure which was fully connected to the hybrid scaffolds and thereby enhanced the biomechanical strength. Together, the biomimetic hybrid MCM-CPC scaffolds enhanced bone defect healing by improved osseointegration and their differentiated degradation provides spatial effects in the process of critical-bone defect healing.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23063400
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Dose-Dependent Effects of a Novel Selective EP4 Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model
    MDPI AG ; 2021
    In:  Biomedicines Vol. 9, No. 11 ( 2021-11-18), p. 1712-
    Details
    In: Biomedicines, MDPI AG, Vol. 9, No. 11 ( 2021-11-18), p. 1712-
    Abstract: Difficulties in treating pseudarthrosis and critical bone defects are still evident in physicians’ clinical routines. Bone morphogenetic protein 2 (BMP-2) has shown promising osteoinductive results but also considerable side effects, not unexpected given that it is a morphogen. Thus, the bone regenerative potential of the novel selective, non-morphogenic EP4 prostaglandin receptor agonist KMN-159 was investigated in this study. Therefore, mineralized collagen type-1 matrices were loaded with different amounts of BMP-2 or KMN-159 and implanted into a 5 mm critical-sized femoral defect in rats. After 12 weeks of observation, micro-computed tomography scans were performed to analyze the newly formed bone volume (BV) and bone mineral density (BMD). Histological analysis was performed to evaluate the degree of defect healing and the number of vessels, osteoclasts, and osteoblasts. Data were evaluated using Kruskal-Wallis followed by Dunn’s post hoc test. As expected, animals treated with BMP-2, the positive control for this model, showed a high amount of newly formed BV as well as bone healing. For KMN-159, a dose-dependent effect on bone regeneration could be observed up to a dose optimum, demonstrating that this non-morphogenic mechanism of action can stimulate bone formation in this model system.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines9111712
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720867-9
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