scholarly journals Reconstruction of Bone Defect Combined with Massive Loss of Periosteum Using Injectable Human Mesenchymal Stem Cells in Biocompatible Ceramic Scaffolds in a Porcine Animal Model

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Chun-Cheng Lin ◽  
Shih-Chieh Lin ◽  
Chao-Ching Chiang ◽  
Ming-Chau Chang ◽  
Oscar Kuang-Sheng Lee
Keyword(s):  
Stem Cells ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Bone Defect ◽  
Soft Tissues ◽  
Bone Defects ◽  
Open Fractures ◽  
Large Animal ◽  
Ceramic Scaffold ◽  
Segmental Bone

Clinically, in patients who sustain severe open fractures, there is not only a segmental bone defect needed to be reconstructed but also insufficient healing capacity due to concomitant damages to the periosteum and surrounding soft tissues. For studying the reconstruction of bone defects associated with massive loss of periosteum and surrounding soft tissues, there are no well-established preclinical models in large animals in the literature. The purpose of the study was to generate a large animal model of bone defect with massive periosteum loss and to adopt a tissue engineering approach to achieve rapid bony union with stem cells and biomaterials. In this study, a bone defect with massive periosteum stripping was generated in pigs, which was followed by emptying nearby canal marrow including fat and cancellous bone. The stripped periosteum was a mimic to the situation in the Gustilo type 3 open fractures. Bone defects were then reconstructed by impacting the biocompatible ceramic scaffold, morselized tricalcium phosphate (TCP) loaded with human adipose tissue-derived mesenchymal stem cells (hMSCs). Radiological and pathological assessments indicated that TCP and hMSCs synergistically promoted bone healing with increased lamination and ingrowth of vessels. Both bridging periosteum formation and gap filling were induced rapidly. In conclusion, a porcine model of segmental bone loss with damage of surrounding periosteum was created. Reconstruction of such defects with hMSCs and TCP achieved rapid union of bone defects associated with massive periosteal stripping.

scholarly journals Biomimetic Methacrylated Gelatin Hydrogel Loaded With Bone Marrow Mesenchymal Stem Cells for Bone Tissue Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Jun Li ◽  
Wenzhao Wang ◽  
Mingxin Li ◽  
Ping Song ◽  
Haoyuan Lei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Extracellular Matrix ◽  
Mesenchymal Stem Cells ◽  
Bone Tissue ◽  
Bone Defect ◽  
Bone Defects ◽  
Biomimetic Materials ◽  
Marrow Mesenchymal Stem Cells ◽  
Segmental Bone

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.

Management of segmental bone defects

2011 ◽  
Author(s):  
Stuart J.E. Matthews
Keyword(s):  
Bone Defect ◽  
Bone Defects ◽  
Open Fractures ◽  
Trauma Surgeon ◽  
Segmental Bone ◽  
Segmental Bone Defects

♦ Segmental defects are a significant, but surmountable, problem for the Trauma surgeon♦ The best results will only be achieved if all potential solutions are considered and used correctly in either: isolation; sequentially; or concurrently.♦ Failure to create a bone defect, during debridement of some open fractures, may be catastrophic. An appreciation of the techniques available to treat segmental defects is necessary to allow the surgeon to debride with confidence.

The association of human mesenchymal stem cells with BMP-7 improves bone regeneration of critical-size segmental bone defects in athymic rats

Bone ◽  
2010 ◽  
Vol 47 (1) ◽  
pp. 117-126 ◽  
Author(s):  
Giorgio Burastero ◽  
Sonia Scarfì ◽  
Chiara Ferraris ◽  
Chiara Fresia ◽  
Nadia Sessarego ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Critical Size ◽  
Human Mesenchymal Stem Cells ◽  
Bone Defects ◽  
Segmental Bone ◽  
Segmental Bone Defects

scholarly journals Brazilian minipig as a large-animal model for basic research and stem cell-based tissue engineering. Characterization and in vitro differentiation of bone marrow-derived mesenchymal stem cells

2014 ◽  
Vol 22 (3) ◽  
pp. 218-227 ◽  
Author(s):  
Roberta Targa STRAMANDINOLI-ZANICOTTI ◽  
André Lopes CARVALHO ◽  
Carmen Lúcia Kuniyoshi REBELATTO ◽  
Laurindo Moacir SASSI ◽  
Maria Fernanda TORRES ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Marrow ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Basic Research ◽  
Large Animal Model ◽  
Large Animal ◽  
In Vitro Differentiation

Abstract WP145: Safety of Intra-Arterial Mesenchymal Stem Cells in a Large Animal Model of Stroke: A Dose Escalation Study

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mitsuyoshi Watanabe ◽  
Karen E Bates ◽  
Luis Guada ◽  
Kevin Ramdas ◽  
Aisha Khan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Dose Escalation ◽  
Cerebral Blood Volume ◽  
Maximum Tolerated Dose ◽  
Large Animal Model ◽  
Large Animal ◽  
Vessel Occlusion ◽  
Dose Escalation Study

Background: Despite the efficacy of thrombectomy for large vessel occlusion acute ischemic stroke (AIS) , ~50% of patients have significant residual deficits. Pre-clinical data on intra-arterially (IA) administered mesenchymal stem cells (MSCs) in stroke are promising and this approach is attractive for clinical application. While there is a concern for micro-occlusion with IA delivery due to the large size of MSCs, a dose of 1 x 10 5 MSCs given 24-48 hr in a rodent reperfusion middle cerebral artery occlusion (rMCAo) model has been shown to be safe and effective. As per STAIR recommendations, we performed a dose-escalation (DE) study of IA-MSCs in a large animal stroke model. Methods: An endovascular canine rMCAo model using retractable platinum coil for 60-120 min was established. At 48 hr post-rMCAo, allogeniec canine MSCs were delivered using a 0.0165” microcatheter in the ipsilateral upper cervical internal carotid artery in escalating doses (based on proportion of rodent to canine total cerebral blood volume). Serial MRIs and neurological deficit scoring (NDS) were performed over 30 days. Animals were euthanized at 15-30 d post-rMCAo and brains were harvested. Results: Female canines (n=13), age 12-36 months, weighing 22-26 kg received IA MSCs ranging from 5-80 x 10 6 (M). At doses of 5-40 M IA-MSCs no neurological worsening was observed. Serial NDS and stroke volume on MRI showed no increase post-IA-MSCs and actually showed progressive reduction. A higher numerical reduction was seen in the 10-40 M groups compared to 5 M. However, in the one canine receiving 80 M IA-MSCs, there was significant worsening of the MCA-area infarction and NDS due to microembolization at this higher dose. Gross examinations and histopathology of brain tissue were consistent with ischemia. The brain of a canine receiving 80 M cells showed differentially aged areas of necrosis supporting two ischemic events. Neuroblasts, doublecortin-positive cells, and neovascularization were observed in canine brains suggesting regenerative mechanisms. Conclusions: These data suggest that IA-MSCs are safe in a large animal model up to 40 M IA-MSCs and is the maximum tolerated dose in this DE study. Furthermore, our data suggests that up to 40 M IA-MSCs may be promising in exploring efficacy in AIS.

scholarly journals Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone Defect

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Jun Li ◽  
Zeyu Huang ◽  
Bohua Li ◽  
Zhengdong Zhang ◽  
Lei Liu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Defect ◽  
Bone Repair ◽  
Self Healing ◽  
Mineral Density ◽  
Segmental Bone Defect ◽  
Marrow Mesenchymal Stem Cells ◽  
Segmental Bone

Reconstruction of segmental bone defects poses a tremendous challenge for both orthopedic clinicians and scientists, since bone rehabilitation is requisite substantially and may be beyond the capacity of self-healing. Bone marrow mesenchymal stem cells (BMSCs) have been identified as an optimal progenitor cell source to facilitate bone repair since they have a higher ability for proliferation and are more easily accessible than mature osteoblastic cells. In spite of the potential of BMSCs in regeneration medicine, particularly for bone reconstruction, noteworthy limitations still remain in previous application of BMSCs, including the amount of cells that could be recruited, the compromised bone migration of grafted cells, reduced proliferation and osteoblastic differentiation ability, and likely tumorigenesis. Our current work demonstrates that BMSCs transplanted through the caudal vein can be mobilized by erythropoietin (EPO) to the bone defect area and participate in regeneration of new bone. Based on the histological analysis and micro-CT findings of this study, EPO can dramatically promote the effects on the osteogenesis and angiogenesis efficiency of BMSCs in vivo. Animals that underwent EPO+BMSC administration demonstrated a remarkable increase in new bone formation, tissue structure organization, new vessel density, callus formation, and bone mineral density (BMD) compared with the BMSCs alone and control groups. At the biomechanical level, we demonstrated that combing transplantation of EPO and BMSCs enhances bone defect reconstruction by increasing the strength of the diaphysis, making it less fragile. Therefore, combination therapy using EPO infusion and BMSC transplantation may be a new therapeutic strategy for the reconstruction of segmental bone defect.

Sign in / Sign up

Export Citation Format

Share Document