3D Printed Hydroxyapatite/Silk Fibroin/Polycaprolactone Artificial Bone Scaffold and Bone Tissue Engineering Materials Constructed with Double-Transfected Bone Morphogenetic Protein-2 and Vascular Endothelial Growth Factor Mesenchymal Stem Cells to Repair Rabbit Radial Bone Defects

2020 ◽  
Vol 12 (3) ◽  
pp. 368-375
Author(s):  
Xu Li ◽  
Fang Ye ◽  
Guoliang Li ◽  
Jun Cui ◽  
Yixiu Liu ◽  
...  

To examine the effect of bone tissue engineering material constructed via 3D printed nanohydroxyapatite/silk fibroin/polycaprolactone (nHA/SF/PCL) artificial bone scaffolds and doubletransfected BMP-2/VEGF mesenchymal stem cells in repairing rabbit radial bone defects, 60 New Zealand rabbits were randomly selected, and with the establishment of a 15 mm bone defect model upon the middle of the anterior right radius bone. The rabbits were randomly divided into 4 groups, with each group composed of 15 rabbits: Group A (nHA/SF/PCL BMP-2/VEGF), Group B (simple nHA/SF/PCL), Group C (simple BMP-2/VEGF), Group D (blank control). Our team recorded the eating, movement, redness, exudation, and so forth across each sample group following the operation. The bone protein expression levels were measured via western blotting following 12 weeks post-operation. Histological observation was carried performed via tissue sections. Following the operation procedure, the wound healed healthily across the 4 experimental groups, no serious infections occurred, only a few rabbits exhibited redness, exudation, pus, and other phenomena, and there was no significant difference present in each group (P > 0.05). The A group took the shortest time to recover its autonomous activity ability, followed by the B group, and the D group took the longest time to recover its autonomous activity ability. From western blotting tests, the A group possessed the highest BMP-2 and OCN expression levels, and have significant difference existed with the B, C, and D group (P < 0.05). The order of expression level of BMP-2 and OCN across the other three groups were group C > group B > group D, respectively. The results of a histological section performed at 12 weeks post-operation revealed that there was no immune response present and no adverse inflammatory reaction occurring within each experimental group. Among the rabbits, the A group exhibited an apparent plate layer new bone formation, bone trabeculae were arranged regularly, and there was no obvious space within the new bone tissue; furthermore, the repair of the bone defect was completed. The B group still exhibited some bone scaffold remaining within the implantation area, and there was a small gap between the new bone tissue, and several bone defects had not been repaired. The C group of bone defects presented only a small number of new bone formation, and bone defect repair effect was not obvious. The D group still possessed large bone defects and exhibited poor repair of bone defects. The nHA/SF/PCL composite of artificial bone scaffold and double-transfected BMP-2/VEGF mesenchymal stem cells was effective in repairing radial bone defects within rabbits, and was superior to using nHA/SF/PCL bone scaffolds alone.

2020 ◽  
Vol 20 (12) ◽  
pp. 7775-7780
Author(s):  
Ziyan Li ◽  
Xiurong Yang ◽  
Shuang Liang ◽  
Hongyi Li ◽  
Linlin Hu ◽  
...  

To observe the effect of nano-artificial bone and bone marrow mesenchymal stem cells (BMSCs) in the treatment of femoral head osteonecrosis. The bilateral femoral head internal bone defect model was established and divided into three groups. Group A was used to make the defect without filling any material as the control, group B was only filled with nano-artificial bone, and group C was filled with composite materials of nano-artificial bone and bone marrow mesenchymal stem cells. The femoral head was examined using radiography and high-resolution focused 48-slice computed tomography (CT) at 12 weeks after implantation. A significant difference was found between groups B and C in the aspect of repairing the defect in osteogenesis of the femoral head as compared with the control group. Nano-collagen-based bone has strong osteogenic and osteogenic effects and is a good graft material for repairing bone defects of the femoral head. The use of bone marrow mesenchymal stem cells can promote the repair of bone defects, which is of great value in the treatment of osteonecrosis of the femoral head.


Author(s):  
Jun Li ◽  
Wenzhao Wang ◽  
Mingxin Li ◽  
Ping Song ◽  
Haoyuan Lei ◽  
...  

Large-segment bone defect caused by trauma or tumor is one of the most challenging problems in orthopedic clinics. Biomimetic materials for bone tissue engineering have developed dramatically in the past few decades. The organic combination of biomimetic materials and stem cells offers new strategies for tissue repair, and the fate of stem cells is closely related to their extracellular matrix (ECM) properties. In this study, a photocrosslinked biomimetic methacrylated gelatin (Bio-GelMA) hydrogel scaffold was prepared to simulate the physical structure and chemical composition of the natural bone extracellular matrix, providing a three-dimensional (3D) template and extracellular matrix microenvironment. Bone marrow mesenchymal stem cells (BMSCS) were encapsulated in Bio-GelMA scaffolds to examine the therapeutic effects of ECM-loaded cells in a 3D environment simulated for segmental bone defects. In vitro results showed that Bio-GelMA had good biocompatibility and sufficient mechanical properties (14.22kPa). A rat segmental bone defect model was constructed in vivo. The GelMA-BMSC suspension was added into the PDMS mold with the size of the bone defect and photocured as a scaffold. BMSC-loaded Bio-GelMA resulted in maximum and robust new bone formation compared with hydrogels alone and stem cell group. In conclusion, the bio-GelMA scaffold can be used as a cell carrier of BMSC to promote the repair of segmental bone defects and has great potential in future clinical applications.


2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Michal Kosinski ◽  
Anna Figiel-Dabrowska ◽  
Wioletta Lech ◽  
Lukasz Wieprzowski ◽  
Ryszard Strzalkowski ◽  
...  

Objective. Bone defects or atrophy may arise as a consequence of injury, inflammation of various etiologies, and neoplastic or traumatic processes or as a result of surgical procedures. Sometimes the regeneration process of bone loss is impaired, significantly slowed down, or does not occur, e.g., in congenital defects. For the bone defect reconstruction, a piece of the removed bone from ala of ilium or bone transplantation from a decedent is used. Replacement of the autologous or allogenic source of the bone-by-bone substitute could reduce the number of surgeries and time in the pharmacological coma during the reconstruction of the bone defect. Application of mesenchymal stem cells in the reconstruction surgery may have positive influence on tissue regeneration by secretion of angiogenic factors, recruitment of other MSCs, or differentiation into osteoblasts. Materials and Methods. Mesenchymal stem cells derived from the umbilical cord (Wharton’s jelly (WJ-MSC)) were cultured in GMP-grade DMEM low glucose supplemented with heparin, 10% platelet lysate, glucose, and antibiotics. In vitro WJ-MSCs were seeded on the bone substitute Bio-Oss Collagen® and cultured in the StemPro® Osteogenesis Differentiation Kit. During the culture on the 1st, 7th, 14th, and 21st day (day in vitro (DIV)), we analyzed viability (confocal microscopy) and adhesion capability (electron microscopy) of WJ-MSC on Bio-Oss scaffolds, gene expression (qPCR), and secretion of proteins (Luminex). In vivo Bio-Oss® scaffolds with WJ-MSC were transplanted to trepanation holes in the cranium to obtain their overgrowth. The computed tomography was performed 7, 14, and 21 days after surgery to assess the regeneration. Results. The Bio-Oss® scaffold provides a favourable environment for WJ-MSC survival. WJ-MSCs in osteodifferentiation medium are able to attach and proliferate on Bio-Oss® scaffolds. Results obtained from qPCR and Luminex® indicate that WJ-MSCs possess the ability to differentiate into osteoblast-like cells and may induce osteoclastogenesis, angiogenesis, and mobilization of host MSCs. In animal studies, WJ-MSCs seeded on Bio-Oss® increased the scaffold integration with host bone and changed their morphology to osteoblast-like cells. Conclusions. The presented construct consisted of Bio-Oss®, the scaffold with high flexibility and plasticity, approved for clinical use with seeded immunologically privileged WJ-MSC which may be considered reconstructive therapy in bone defects.


2009 ◽  
Vol 78 (4) ◽  
pp. 635-642 ◽  
Author(s):  
Michal Crha ◽  
Alois Nečas ◽  
Robert Srnec ◽  
Jan Janovec ◽  
Ladislav Stehlík ◽  
...  

This synoptic study gives a concise overview of current knowledge of bone healing, the role of mesenchymal stem cells in bone tissue regeneration and contemporary possibilities of supporting regeneration of damaged bone. Attention of research concerning the healing of fractures with extensive loss of bone tissue following trauma, the treatment of belatedly healing or non-healing fractures or the healing of segmental bone defects following tumour resection, is focused on development of three-dimensional scaffolds planted with mesenchymal stem cells that might be used for reconstruction of such large bone lesions. Presented are possibilities of transplantation of mesenchymal stem cells combined with biomaterials into bone defects, including the results of our own experimental studies dealing with the use of stem cells in the treatment of damaged tissues of the musculoskeletal system in animal models.


2018 ◽  
Vol 374 (1) ◽  
pp. 63-81 ◽  
Author(s):  
Ahmad Oryan ◽  
Mohamadreza Baghaban Eslaminejad ◽  
Amir Kamali ◽  
Samaneh Hosseini ◽  
Ali Moshiri ◽  
...  

2020 ◽  
Vol 21 (16) ◽  
pp. 5816
Author(s):  
Kar Wey Yong ◽  
Jane Ru Choi ◽  
Jean Yu Choi ◽  
Alistair C. Cowie

Large bone defects are a major health concern worldwide. The conventional bone repair techniques (e.g., bone-grafting and Masquelet techniques) have numerous drawbacks, which negatively impact their therapeutic outcomes. Therefore, there is a demand to develop an alternative bone repair approach that can address the existing drawbacks. Bone tissue engineering involving the utilization of human mesenchymal stem cells (hMSCs) has recently emerged as a key strategy for the regeneration of damaged bone tissues. However, the use of tissue-engineered bone graft for the clinical treatment of bone defects remains challenging. While the role of mechanical loading in creating a bone graft has been well explored, the effects of mechanical loading factors (e.g., loading types and regime) on clinical outcomes are poorly understood. This review summarizes the effects of mechanical loading on hMSCs for bone tissue engineering applications. First, we discuss the key assays for assessing the quality of tissue-engineered bone grafts, including specific staining, as well as gene and protein expression of osteogenic markers. Recent studies of the impact of mechanical loading on hMSCs, including compression, perfusion, vibration and stretching, along with the potential mechanotransduction signalling pathways, are subsequently reviewed. Lastly, we discuss the challenges and prospects of bone tissue engineering applications.


2010 ◽  
Vol 79 (4) ◽  
pp. 607-612 ◽  
Author(s):  
Alois Nečas ◽  
Pavel Proks ◽  
Lucie Urbanová ◽  
Robert Srnec ◽  
Ladislav Stehlík ◽  
...  

At present, attention is focused on research into possibilities of healing large bone defects by the method of mini-invasive osteosynthesis, using implantation of biomaterials and mesenchymal stem cells (MSCs). This study evaluates the healing of segmental femoral defects in miniature pigs based on the radiological determination of the callus: cortex ratio at 16 weeks after ostectomy. The size of the formed callus was significantly larger (p < 0.05) in animals after transplantation of an autogenous cancellous bone graft (group A, callus : cortex ratio of 1.77 ± 0.33) compared to animals after transplantation of cylindrical scaffold from hydroxyapatite and 0.5% collagen (group S, callus : cortex ratio of 1.08 ± 0.13), or in animals after transplantation of this scaffold seeded with MSCs (group S + MSCs, callus: cortex ratio of 1.15 ± 0.18). No significant difference was found in the size of callus between animals of group S and animals of group S + MSCs. Unlike a scaffold in the shape of the original bone column, a freely placed autogenous cancellous bone graft may allow the newly formed tissue to spread more to the periphery of the ostectomy defect. Implanted cylindrical scaffolds (with and without MSCs) support callus formation directly in the center of original bone column in segmental femoral ostectomy, and can be successfully used in the treatment of large bone defects.


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