scholarly journals In vivo safety and efficacy testing of a thermally triggered injectable hydrogel scaffold for bone regeneration and augmentation in a rat model

Oncotarget ◽  
2018 ◽  
Vol 9 (26) ◽  
pp. 18277-18295 ◽  
Author(s):  
Abbey A. Thorpe ◽  
Christine Freeman ◽  
Paula Farthing ◽  
Jill Callaghan ◽  
Paul V. Hatton ◽  
...  
2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Feng Wang ◽  
Li-ping Nan ◽  
Shi-feng Zhou ◽  
Yang Liu ◽  
Ze-yu Wang ◽  
...  

Stem cell-based tissue engineering in treating intervertebral disc (IVD) degeneration is promising. An appropriate cell scaffold can maintain the viability and function of transplanted cells. Injectable hydrogel has the potential to be an appropriate cell scaffold as it can mimic the condition of the natural extracellular matrix (ECM) of nucleus pulposus (NP) and provide binding sites for cells. This study was aimed at investigating the effect of injectable hydrogel-loaded NP-derived mesenchymal stem cells (NPMSC) for the treatment of IVD degeneration (IDD) in rats. In this study, we selected injectable 3D-RGD peptide-modified polysaccharide hydrogel as a cell transplantation scaffold. In vitro, the biocompatibility, microstructure, and induced differentiation effect on NPMSC of the hydrogel were studied. In vivo, the regenerative effect of hydrogel-loaded NPMSC on degenerated NP in a rat model was evaluated. The results showed that NPMSC was biocompatible and able to induce differentiation in hydrogel in vivo. The disc height index (almost 87%) and MRI index (3313.83±227.79) of the hydrogel-loaded NPMSC group were significantly higher than those of other groups at 8 weeks after injection. Histological staining and immunofluorescence showed that the hydrogel-loaded NPMSC also partly restored the structure and ECM content of degenerated NP after 8 weeks. Moreover, the hydrogel could support long-term NPMSC survival and decrease cell apoptosis rate of the rat IVD. In conclusion, injectable hydrogel-loaded NPMSC transplantation can delay the level of IDD and promote the regeneration of the degenerative IVD in the rat model.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Bo Liang ◽  
Jia-Ming Liang ◽  
Jia-Ning Ding ◽  
Jia Xu ◽  
Jian-Guang Xu ◽  
...  

Abstract Background Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidate agents for treating critical-sized bone defects; they promote angiogenesis and may be an alternative to cell therapy. In this study, we evaluated whether exosomes derived from bone marrow-derived MSCs (BMSCs) preconditioned with a low dose of dimethyloxaloylglycine (DMOG), DMOG-MSC-Exos, exert superior proangiogenic activity in bone regeneration and the underlying mechanisms involved. Methods To investigate the effects of these exosomes, scratch wound healing, cell proliferation, and tube formation assays were performed in human umbilical vein endothelial cells (HUVECs). To test the effects in vivo, a critical-sized calvarial defect rat model was established. Eight weeks after the procedure, histological/histomorphometrical analysis was performed to measure bone regeneration, and micro-computerized tomography was used to measure bone regeneration and neovascularization. Results DMOG-MSC-Exos activated the AKT/mTOR pathway to stimulate angiogenesis in HUVECs. This contributed to bone regeneration and angiogenesis in the critical-sized calvarial defect rat model in vivo. Conclusions Low doses of DMOG trigger exosomes to exert enhanced proangiogenic activity in cell-free therapeutic applications.


2021 ◽  
Vol 5 (2) ◽  
pp. 2000106
Author(s):  
Yuka Kimura ◽  
Seika Aoyama ◽  
Natsumi Ueda ◽  
Tokitaka Katayama ◽  
Kimika Ono ◽  
...  

2020 ◽  
Vol 10 (5) ◽  
pp. 1651 ◽  
Author(s):  
Abeer G. Ahmed ◽  
Fatin A. Awartani ◽  
Abdurahman A. Niazy ◽  
John A. Jansen ◽  
Hamdan S. Alghamdi

The aim of this in vivo study was to evaluate the efficacy of biphasic calcium phosphate (Maxresorb®, BCP) used in combination with hyaluronic acid (Hyadent®, HyA) gel for regeneration of osseous defects in a rat model. Bilateral femoral condylar bone defects (3 mm diameter and 3 mm depth) were created in 40 male Wistar rats. The defects were grafted as group I (BCP only), group II (BCP + HyA), group III (HyA only), and group IV (empty control). At four weeks and 10 weeks, the bone specimens were evaluated using histological and histomorphometrical analyses to identify the newly formed bone area (NF-BA (%)), as well as the remaining BCP particles (R-BCP (%)). Light microscopic examination indicated the absence of an inflammatory reaction within the bone defects after four weeks or 10 weeks of implantation. Significant new bone regeneration was present in the bone defects grafted with BCP or BCP + HyA biomaterials, as early as four weeks, compared to control groups. The addition of HyA to BCP did not significantly improve bone regeneration at four weeks or 10 weeks. Nevertheless, its role in bone healing and regeneration warrants further investigation.


2012 ◽  
Vol 28 (1) ◽  
pp. 3-15 ◽  
Author(s):  
Roberto Solaro ◽  
Michele Alderighi ◽  
Maria C Barsotti ◽  
Antonella Battisti ◽  
Mario Cifelli ◽  
...  

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.


2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S392-S392
Author(s):  
Nadja Van Camp ◽  
Koen Van Laere ◽  
Ruth Vreys ◽  
Marleen Verhoye ◽  
Erwin Lauwers ◽  
...  

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