scholarly journals The Co-Culture of ASCs and EPCs Promotes Vascularized Bone Regeneration in Critical-Sized Bone Defects of Cranial Bone in Rats

2020 ◽  
Author(s):  
yuanjia he ◽  
Shuang Lin ◽  
Qiang Ao ◽  
Xiaoning He
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Defect ◽  
Culture System ◽  
Donor Site ◽  
Bone Defects ◽  
Cranial Bone ◽  
Vascularized Bone

Abstract Background: The repair of critical-sized bone defect represents a challenging problem in bone tissue engineering. To address the most important problem in bone defect repair, namely insufficient blood supply, this study aimed to find a method that can promote the formation of vascularized bone tissue.Method The phenotypes of ASCs and EPCs were identified respectively, and ASCs/EPCs were co-cultured in vitro to detect the expression of osteogenic and angiogenic genes. Furthermore, the co-culture system combined with scaffold material was used to repair the critical-sized bone defects of the cranial bone in rats.Results The co-culture of ASCs/EPCs could increase osteogenesis and angiogenesis-related gene expression in vitro. The results of in vivo animal experiments demonstrated that the ASCs/EPCs group could promote bone regeneration and vascularization in the meantime and, then significantly accelerate the repair of critical-sized bone defects.Conclusion It is feasible to replace traditional single seed cells with ASCs/EPCs co-culture system for vascularized bone regeneration. This system could ultimately enable clinicians to better repair the defect of craniofacial bone and avoid donor site morbidity.

scholarly journals The Co-Culture of ASCs and EPCs Promotes Vascularized Bone Regeneration in Critical-Sized Bone Defects of Cranial Bone in Rats

2020 ◽  
Author(s):  
yuanjia he ◽  
Shuang Lin ◽  
Qiang Ao ◽  
Xiaoning He
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Defect ◽  
Culture System ◽  
Donor Site ◽  
Bone Defects ◽  
Cranial Bone ◽  
Vascularized Bone

Abstract Background: The repair of critical-sized bone defect represents a challenging problem in bone tissue engineering. To address the most important problem in bone defect repair, namely insufficient blood supply, this study aimed to find a method that can promote the formation of vascularized bone tissue.Method The phenotypes of ASCs and EPCs were identified respectively, and ASCs/EPCs were co-cultured in vitro to detect the expression of osteogenic and angiogenic genes. Furthermore, the co-culture system combined with scaffold material was used to repair the critical-sized bone defects of the cranial bone in rats.Results The co-culture of ASCs/EPCs could increase osteogenesis and angiogenesis-related gene expression in vitro. The results of in vivo animal experiments demonstrated that the ASCs/EPCs group could promote bone regeneration and vascularization in the meantime and, then significantly accelerate the repair of critical-sized bone defects.Conclusion It is feasible to replace traditional single seed cells with ASCs/EPCs co-culture system for vascularized bone regeneration. This system could ultimately enable clinicians to better repair the defect of craniofacial bone and avoid donor site morbidity.

scholarly journals Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

2017 ◽  
Vol 8 ◽  
pp. 204173141771207 ◽  
Author(s):  
Mathieu Maisani ◽  
Daniele Pezzoli ◽  
Olivier Chassande ◽  
Diego Mantovani
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Repair ◽  
Critical Issue ◽  
Bone Defects ◽  
Bone Tissue Regeneration ◽  
Differentiation Potential ◽  
Promising Alternative

Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.

scholarly journals Low level laser therapy promotes bone regeneration by coupling angiogenesis and osteogenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Bai ◽  
Lijun Li ◽  
Ni Kou ◽  
Yuwen Bai ◽  
Yaoyang Zhang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Low Level Laser Therapy ◽  
Level Laser ◽  
Vascularized Bone

Abstract Background Bone tissue engineering is a new concept bringing hope for the repair of large bone defects, which remains a major clinical challenge. The formation of vascularized bone is key for bone tissue engineering. Growth of specialized blood vessels termed type H is associated with bone formation. In vivo and in vitro studies have shown that low level laser therapy (LLLT) promotes angiogenesis, fracture healing, and osteogenic differentiation of stem cells by increasing reactive oxygen species (ROS). However, whether LLLT can couple angiogenesis and osteogenesis, and the underlying mechanisms during bone formation, remains largely unknown. Methods Mouse bone marrow mesenchymal stem cells (BMSCs) combined with biphasic calcium phosphate (BCP) grafts were implanted into C57BL/6 mice to evaluate the effects of LLLT on the specialized vessel subtypes and bone regeneration in vivo. Furthermore, human BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. The effects of LLLT on cell proliferation, angiogenesis, and osteogenesis were assessed. Results LLLT promoted the formation of blood vessels, collagen fibers, and bone tissue and also increased CD31hiEMCNhi-expressing type H vessels in mBMSC/BCP grafts implanted in mice. LLLT significantly increased both osteogenesis and angiogenesis, as well as related gene expression (HIF-1α, VEGF, TGF-β) of grafts in vivo and of co-cultured BMSCs/HUVECs in vitro. An increase or decrease of ROS induced by H2O2 or Vitamin C, respectively, resulted in an increase or decrease of HIF-1α, and a subsequent increase and decrease of VEGF and TGF-β in the co-culture system. The ROS accumulation induced by LLLT in the co-culture system was significantly decreased when HIF-1α was inhibited with DMBPA and was followed by decreased expression of VEGF and TGF-β. Conclusions LLLT enhanced vascularized bone regeneration by coupling angiogenesis and osteogenesis. ROS/HIF-1α was necessary for these effects of LLLT. LLLT triggered a ROS-dependent increase of HIF-1α, VEGF, and TGF-β and resulted in subsequent formation of type H vessels and osteogenic differentiation of mesenchymal stem cells. As ROS also was a target of HIF-1α, there may be a positive feedback loop between ROS and HIF-1α, which further amplified HIF-1α induction via the LLLT-mediated ROS increase. This study provided new insight into the effects of LLLT on vascularization and bone regeneration in bone tissue engineering.

scholarly journals Construction of hollow polydopamine nanoparticle based drug sustainable release system and its application in bone regeneration

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Lu Wang ◽  
Shuwei Liu ◽  
Chunxia Ren ◽  
Siyuan Xiang ◽  
Daowei Li ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Load Capacity ◽  
Good Prospect ◽  
Alizarin Red ◽  
Drug Load ◽  
Load Rate ◽  
Low Toxicity

AbstractNanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.

scholarly journals Activation of Mesenchymal Stem Cells Promotes New Bone Formation Within Dentigerous Cyst

2020 ◽  
Author(s):  
Yejia Yu ◽  
Mengyu Li ◽  
Yuqiong Zhou ◽  
Yueqi Shi ◽  
Wenjie Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Dentigerous Cyst ◽  
Healing Process ◽  
Cell Counting ◽  
Cranial Bone ◽  
Alizarin Red

Abstract Background: Dentigerous cyst (DC) is a bone destructive disease and remains a challenge for clinicians. Marsupialization enables bone to regenerate with capsules maintaining, making it a preferred therapeutic means for DC adjacent to vital anatomical structures. Given that capsules of DC derive from odontogenic epithelium remnants at embryonic stage, we investigated whether there were mesenchymal stem cells (MSCs) located in DC capsules and the role that they played in the bone regeneration after marsupialization.Methods: Samples obtained before and after marsupialization were used for histological detection and cell culture. The stemness of cells isolated from fresh tissues were analyzed by morphology, surface marker and multi-differentiation assays. Comparison of proliferation ability between Am-DCSCs and Bm-DCSCs were evaluated by Cell Counting Kit-8 (CCK-8), fibroblast colony-forming units (CFU-F) and 5’‐ethynyl‐2’‐deoxyuridine (EdU) assay. Their osteogenic capacity in vitro was detected by Alkaline phosphatase (ALP) and Alizarin Red staining (ARS), combined with Real-time polymerase chain reaction (RT-PCR) and immunofluorescence (IF) staining. Subcutaneous ectopic osteogenesis as well as cranial bone defect model in nude mice were performed to detect their bone regeneration and bone defect repair ability.Results: Bone tissue and strong ALP activity were detected in the capsule of DC after marsupialization. Two types of MSCs were isolated from fibrous capsules of DC both before (Bm-DCSCs) and after (Am-DCSCs) marsupialization. These fibroblast-like, colony forming cells expressed MSC markers (CD44+, CD90+, CD31-, CD34-, CD45-), and they could differentiate into osteoblast-, adipocyte- and chondrocyte-like cells under induction. Notably, Am-DCSCs performed better in cell proliferation and self-renewal. Moreover, Am-DCSCs showed greater osteogenic capacity both in vitro and in vivo compared with Bm-DCSCs. Conclusions: There are MSCs residing in capsules of DC, and the cell viability as well as osteogenic capacity of them are largely enhanced after marsupialization. Our findings suggested that MSCs might play a crucial role in the healing process of DC after marsupialization, thus providing new insight into the treatment for DC by promoting the osteogenic differentiation of MSCs inside capsules.

scholarly journals Increased BMSC Exosomal miR-140-3p Alleviates Bone Degradation and Promotes Bone Restoration by Targeting Plxnb1 in Diabetic Rats

2021 ◽  
Author(s):  
Ning Wang ◽  
Xuanchen Liu ◽  
Zhen Tang ◽  
Xinghui Wei ◽  
Hui Dong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Diabetic Rats ◽  
Osteogenic Potential ◽  
Bone Degradation ◽  
Defect Repair

Abstract Background: Diabetes mellitus (DM) is considered to be an important factor for bone degeneration disorders such as bone defect nonunion, which is characterized by physical disability and tremendous economy cost to families and society. Exosomal miRNAs of BMSCs have been reported to participate in osteoblastogenesis and modulating bone formation. However, their impacts on the development of bone degeneration in DM are not yet known. The role of miRNAs in BMSCs exosomes on regulating hyperglycemia bone degeneration was investigated in the present study. Results: The osteogenic potential in bone defect repair of exosomes derived from diabetes mellitus BMSCs derived exosomes (DM-Exos) were revealed to be lower than that in normal BMSCs derived exosomes (N-Exos) in vitro and in vivo. Here, we demonstrate that miR-140-3p level was significantly altered in exosomes derived from BMSCs, ADSCs and serum from DM rats. In in vitro experiments, upregulated miR-140-3p exosomes promoted DM BMSCs differentiation into osteoblasts. The effects were exerted by miR-140-3p targeting plxnb1, plexin B1 is the receptor of semaphoring 4D(Sema4D) that inhibited osteocytes differentiation, thereby promoting bone formation. In DM rats with bone defect, miR-140-3p upregulated exosomes were transplanted into injured bone and accelerated bone regeneration. Besides, miR-140-3p in the exosomes was transferred into BMSCs and osteoblasts and promoted bone regeneration by targeting the plexin B1/RohA/ROCK signaling pathway. Conclusions: Normal-Exos and miR-140-3p overexpressed-Exos accelerated diabetic wound healing by promoting the osteoblastogenesis function of BMSCs through inhibition plexin B1 expression which is the receptor of Sema4D and the plexin B1/RhoA/ROCK pathway compared with diabetes mellitus-Exos. This offers a new insight and a new therapy for treating diabetic bone unhealing.

scholarly journals Biomaterials with structural hierarchy and controlled 3D nanotopography guide endogenous bone regeneration

2021 ◽  
Vol 7 (31) ◽  
pp. eabg3089
Author(s):  
Shixuan Chen ◽  
Hongjun Wang ◽  
Valerio Luca Mainardi ◽  
Giuseppe Talò ◽  
Alec McCarthy ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Three Dimensional ◽  
Cranial Bone ◽  
Mineral Density ◽  
Structural Hierarchy ◽  
Packed Structure ◽  
Inorganic Mineral ◽  
Distribution Of Stress

Biomaterials without exogenous cells or therapeutic agents often fail to achieve rapid endogenous bone regeneration with high quality. Here, we reported a class of three-dimensional (3D) nanofiber scaffolds with hierarchical structure and controlled alignment for effective endogenous cranial bone regeneration. 3D scaffolds consisting of radially aligned nanofibers guided and promoted the migration of bone marrow stem cells from the surrounding region to the center in vitro. These scaffolds showed the highest new bone volume, surface coverage, and mineral density among the tested groups in vivo. The regenerated bone exhibited a radially aligned fashion, closely recapitulating the scaffold’s architecture. The organic phase in regenerated bone showed an aligned, layered, and densely packed structure, while the inorganic mineral phase showed a uniform distribution with smaller pore size and an even distribution of stress upon the simulated compression. We expect that this study will inspire the design of next-generation biomaterials for effective endogenous bone regeneration with desired quality.

scholarly journals Activation of mesenchymal stem cells promotes new bone formation within dentigerous cyst

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yejia Yu ◽  
Mengyu Li ◽  
Yuqiong Zhou ◽  
Yueqi Shi ◽  
Wenjie Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Dentigerous Cyst ◽  
Healing Process ◽  
Cell Counting ◽  
Cranial Bone ◽  
Alizarin Red

Abstract Background Dentigerous cyst (DC) is a bone destructive disease and remains a challenge for clinicians. Marsupialization enables the bone to regenerate with capsule maintaining, making it a preferred therapeutic means for DC adjacent to vital anatomical structures. Given that capsules of DC are derived from odontogenic epithelium remnants at the embryonic stage, we investigated whether there were mesenchymal stem cells (MSCs) located in DC capsules and the role that they played in the bone regeneration after marsupialization. Methods Samples obtained before and after marsupialization were used for histological detection and cell culture. The stemness of cells isolated from fresh tissues was analyzed by morphology, surface marker, and multi-differentiation assays. Comparison of proliferation ability between MSCs isolated from DC capsules before (Bm-DCSCs) and after (Am-DCSCs) marsupialization was evaluated by Cell Counting Kit-8 (CCK-8), fibroblast colony-forming units (CFU-F), and 5′-ethynyl-2′-deoxyuridine (EdU) assay. Their osteogenic capacity in vitro was detected by alkaline phosphatase (ALP) and Alizarin Red staining (ARS), combined with real-time polymerase chain reaction (RT-PCR) and immunofluorescence (IF) staining. Subcutaneous ectopic osteogenesis as well as cranial bone defect model in nude mice was performed to detect their bone regeneration and bone defect repairability. Results Bone tissue and strong ALP activity were detected in the capsule of DC after marsupialization. Two types of MSCs were isolated from fibrous capsules of DC both before (Bm-DCSCs) and after (Am-DCSCs) marsupialization. These fibroblast-like, colony-forming cells expressed MSC markers (CD44+, CD90+, CD31−, CD34−, CD45−), and they could differentiate into osteoblast-, adipocyte-, and chondrocyte-like cells under induction. Notably, Am-DCSCs performed better in cell proliferation and self-renewal. Moreover, Am-DCSCs showed a greater osteogenic capacity both in vitro and in vivo compared with Bm-DCSCs. Conclusions There are MSCs residing in capsules of DC, and the cell viability as well as the osteogenic capacity of them is largely enhanced after marsupialization. Our findings suggested that MSCs might play a crucial role in the healing process of DC after marsupialization, thus providing new insight into the treatment for DC by promoting the osteogenic differentiation of MSCs inside capsules.

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