Xeno-Hybrid Bone Graft Releasing Biomimetic Proteins Promotes Osteogenic Differentiation of hMSCs

Bone defect is a noteworthy health problem and is the second most transplanted tissue after blood. Numerous bone grafts are designed and applied in clinics. Limitations, however, from different aspects still exist, including limited supply, mechanical strength, and bioactivity. In this study, two biomimetic peptides (P2 and P6) are incorporated into a composite bioactive xeno hybrid bone graft named SmartBonePep®, with the aim to increase the bioactivity of the bone graft. The results, which include cytotoxicity, proliferation rate, confocal microscopy, gene expression, and protein qualification, successfully prove that the SmartBonePep® has multi-modal biological effects on human mesenchymal stem cells from bone marrow. The effective physical entrapment of P6 into a composite xeno-hybrid bone graft, withstanding manufacturing processes including exposure to strong organic solvents and ethylene oxide sterilization, increases the osteogenic potential of the stem cells as well as cell attachment and proliferation. P2 and P6 both show a strong biological potential and may be future candidates for enhancing the clinical performance of bone grafts.

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In VitroCharacterization of Human Mesenchymal Stem Cells Isolated from Different Tissues with a Potential to Promote Complex Bone Regeneration

Stem Cells International ◽

10.1155/2016/3595941 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 17

Author(s):

Áron Szepesi ◽

Zsolt Matula ◽

Anna Szigeti ◽

György Várady ◽

József Szalma ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Periodontal Ligament ◽

Human Mesenchymal Stem Cells ◽

Bone Grafts ◽

Bone Tissue Regeneration ◽

Osteogenic Potential ◽

Medical Need

Bone tissue regeneration is a major, worldwide medical need, and several strategies have been developed to support the regeneration of extensive bone defects, including stem cell based bone grafts. In addition to the application of stem cells with high osteogenic potential, it is important to maintain proper blood flow in a bone graft to avoid inner graft necrosis. Mesenchymal stem cells (MSCs) may form both osteocytes and endothelial cells; therefore we examined the combinedin vitroosteogenic and endothelial differentiation capacities of MSCs derived from adipose tissue, Wharton’s jelly, and periodontal ligament. Based on a detailed characterization presented here, MSCs isolated from adipose tissue and periodontal ligament may be most appropriate for generating vascularized bone grafts.

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In Vivo Study for Clinical Application of Dental Stem Cell Therapy Incorporated with Dental Titanium Implants

Materials ◽

10.3390/ma14020381 ◽

2021 ◽

Vol 14 (2) ◽

pp. 381

Author(s):

Hyunmin Choi ◽

Kyu-Hyung Park ◽

Narae Jung ◽

June-Sung Shim ◽

Hong-Seok Moon ◽

...

Keyword(s):

Stem Cells ◽

Bone Formation ◽

Alveolar Bone ◽

Human Mesenchymal Stem Cells ◽

Titanium Implants ◽

Osteogenic Potential ◽

Induction Medium ◽

Radiographic Analysis ◽

New Bone Formation

The aim of this study was to investigate the behavior of dental-derived human mesenchymal stem cells (d-hMSCs) in response to differently surface-treated implants and to evaluate the effect of d-hMSCs on local osteogenesis around an implant in vivo. d-hMSCs derived from alveolar bone were established and cultured on machined, sandblasted and acid-etched (SLA)-treated titanium discs with and without osteogenic induction medium. Their morphological and osteogenic potential was assessed by scanning electron microscopy (SEM) and real-time polymerase chain reaction (RT-PCR) via mixing of 5 × 106 of d-hMSCs with 1 mL of Metrigel and 20 μL of gel-cell mixture, which was dispensed into the defect followed by the placement of customized mini-implants (machined, SLA-treated implants) in New Zealand white rabbits. Following healing periods of 2 weeks and 12 weeks, the obtained samples in each group were analyzed radiographically, histomorphometrically and immunohistochemically. The quantitative change in osteogenic differentiation of d-hMSCs was identified according to the type of surface treatment. Radiographic analysis revealed that an increase in new bone formation was statistically significant in the d-hMSCs group. Histomorphometric analysis was in accordance with radiographic analysis, showing the significantly increased new bone formation in the d-hMSCs group regardless of time of sacrifice. Human nuclei A was identified near the area where d-hMSCs were implanted but the level of expression was found to be decreased as time passed. Within the limitations of the present study, in this animal model, the transplantation of d-hMSCs enhanced the new bone formation around an implant and the survival and function of the stem cells was experimentally proven up to 12 weeks post-sacrifice.

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Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation

Journal of Cellular Biochemistry ◽

10.1002/(sici)1097-4644(199702)64:2<278::aid-jcb11>3.0.co;2-f ◽

1997 ◽

Vol 64 (2) ◽

pp. 278-294 ◽

Cited By ~ 971

Author(s):

Scott P. Bruder ◽

Neelam Jaiswal ◽

Stephen E. Haynesworth

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Growth Kinetics ◽

Human Mesenchymal Stem Cells ◽

Osteogenic Potential ◽

Self Renewal

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Osteogenic Potential of Autogenous Bone Grafts Harvested with Four Different Surgical Techniques

Journal of Dental Research ◽

10.1177/0022034511422718 ◽

2011 ◽

Vol 90 (12) ◽

pp. 1428-1433 ◽

Cited By ~ 61

Author(s):

R.J. Miron ◽

E. Hedbom ◽

N. Saulacic ◽

Y. Zhang ◽

A. Sculean ◽

...

Keyword(s):

Cell Attachment ◽

Surgical Techniques ◽

Bone Grafts ◽

Osteogenic Potential ◽

Autogenous Bone ◽

Mrna Levels ◽

Alizarin Red ◽

Osteogenic Response ◽

Autogenous Bone Grafts

The osteogenic potential of autogenous bone grafts is superior to that of allografts and xenografts because of their ability to release osteoinductive growth factors and provide a natural osteoconductive surface for cell attachment and growth. In this in vitro study, autogenous bone particles were harvested by four commonly used techniques and compared for their ability to promote an osteogenic response. Primary osteoblasts were isolated and seeded on autogenous bone grafts prepared from the mandibles of miniature pigs with a bone mill, piezo-surgery, bone scraper, and bone drill (bone slurry). The osteoblast cultures were compared for their ability to promote cell attachment, proliferation, and differentiation. After 4 and 8 hrs, significantly higher cell numbers were associated with bone mill and bone scraper samples compared with those acquired by bone slurry and piezo-surgery. Similar patterns were consistently observed up to 5 days. Furthermore, osteoblasts seeded on bone mill and scraper samples expressed significantly elevated mRNA levels of collagen, osteocalcin, and osterix at 3 and 14 days and produced more mineralized tissue as assessed by alizarin red staining. These results suggest that the larger bone graft particles produced by bone mill and bone scraper techniques have a higher osteogenic potential than bone slurry and piezo-surgery.

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In vitro Investigation of Mesenchymal Stem Cells with Nanophase PLGA/HA Composite

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.330-332.1153 ◽

2007 ◽

Vol 330-332 ◽

pp. 1153-1156 ◽

Cited By ~ 1

Author(s):

Jie Feng ◽

Qiang Zheng ◽

Zhong Li Shi ◽

Hong Liang Jiang ◽

Wei Qi Yan

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Tissue ◽

Cell Attachment ◽

Biological Response ◽

Bone Grafts ◽

Mesenchymal Cells ◽

Allogenic Bone ◽

In Vitro Investigation

Bone grafts have been used to fill bone defects caused by disease or trauma. The amount of autografts is limited and allogenic bone grafts may transmit diseases and cause immune responses. Numerous materials have been proposed and used as scaffolds for bone tissue reconstruction. In this study, we tested nanophase PLGA/HA composite with mesenchymal stem cells in vitro to examine its biological response and cellular activity. The nanophase composite was compared to conventional polystyrene on cytocompatibility by cell attachment, proliferation, alkaline phosphotase activity test and scanning electron microscopy (SEM) analysis. The results demonstrated that human mesenchymal cells showed more cell attachment and higher cell proliferation rate when growing on nanophase PLGA/HA composite than those growing on polystyrene alone. And the composite also promoted MSC cells differentiate to osteoblast cells as compared with control. It was suggested that the combination of bone marrow mesenchymal cells with artificial materials or differentiation factors may enhance bone formation and regeneration, nanophase PLGA/HA composite might therefore be a promising scaffold material for bone tissue substitute in clinical application.

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