scholarly journals ID: 1058 Effective bone formation through BMP-2-immobilized highly porous GBR membrane

2017 ◽  
Vol 4 (S) ◽  
pp. 139
Author(s):  
Min Ji Kim ◽  
Jin Hyun Park ◽  
Ho Yong Kim ◽  
June Ho Byun ◽  
Jin Ho Lee ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Active Sites ◽  
Healing Process ◽  
The Body ◽  
Bioactive Molecules ◽  
Bone Morphogenetic Protein 2 ◽  
Gbr Membrane

Sound healing of large bone defects is critical challenges in most of clinical fields. In general healing process of bone regeneration, the rapid infiltration of connective tissue, whereas relatively slow bone regeneration in bone defect leads to the incomplete bone formation. To solve this drawback, guide bone regeneration (GBR) membrane which could prevent rapid infiltration of connective tissue into bone defect, thus GBR membrane is feasible for compact bone regeneration in clinical fields. In recent, the most researchers believed that bioactive molecules-grafted GBR membranes may enhance the bone regeneration. To allow graft of bioactive molecules from porous membrane, chemically modified scaffolds are commonly used. This modification leads to sufficient interaction with active sites of bioactive molecules to stable the immobilization of bioactive molecules in the body. However it is hard to apply to clinical applications because of the toxicity of chemical residue used for the modification. In this study, we developed a GBR membrane with leaf-stacked structure which can allow sustained release of bone morphogenetic protein-2 (BMP-2) without any additional modification. The morphology, mechanical property, BMP-2 release profile, osteogenic differentiation of human periosteum-derived cells, and new bone formation efficiency of the BMP-2-loaded GBR membrane compared with commercial product were investigated.

scholarly journals Effect of Stromal Vascular Fraction on Fracture Healing with Bone Defects by Examination of Bone Morphogenetic Protein-2 Biomarkers in Murine Model

2021 ◽  
Vol 9 (A) ◽  
pp. 1132-1136
Author(s):  
Respati S. Dradjat ◽  
Panji Sananta ◽  
Rizqi Daniar Rosandi ◽  
Lasa Dhakka Siahaan
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Bone Defect ◽  
Murine Model ◽  
Healing Process ◽  
Stromal Vascular Fraction ◽  
Bone Defects ◽  
The Body ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein

BACKGROUND: Fractures and segmental bone defects are a significant cause of morbidity and a source of a high economic burden in healthcare. A severe bone defect (3 mm in murine model) is a devastating condition, which the bone cannot heal naturally despite surgical stabilization and usually requires further surgical intervention. The stromal vascular fraction (SVF) contains a heterogeneous collection of cells and several components, primarily: MSCs, HSCs, Treg cells, pericytic cells, AST cells, extracellular matrix, and complex microvascular beds (fibroblasts, white blood cells, dendritic cells, and intra-adventitial smooth muscular-like cells). Bone morphogenetic protein (BMP) is widely known for their important role in bone formation during mammalian development and confers a multifunctional role in the body, which has potential for therapeutic use. Studies have shown that BMPs play a role in the healing of large size bone defects. AIM: In this study, researchers aim to determine the effect of administering SVF from adipose tissue on the healing process of bone defects assessed based on the level biomarker of BMP-2. MATERIALS AND METHODS: This was an animal study involving 12 Wistar strain Rattus norvegivus. They were divided into three groups: Negative group (normal rats), positive group (rats with bone defect without SVF application), and SVF group (rats with bone defect with SVF application). After 30 days, the rats were sacrificed; the biomarkers that were evaluated are BMP-2. This biomarker was quantified using ELISA. RESULTS: BMP-2 biomarker expressions were higher in the SVF application group than in the group without SVF. All comparisons of the SVF group and positive control group showed significant differences (p = 0.026). CONCLUSION: SVF application could aid the healing process in a murine model with bone defect marked by the increased level of BMP-2 as a bone formation marker.

scholarly journals The Bone Regeneration Capacity of BMP-2 + MMP-10 Loaded Scaffolds Depends on the Tissue Status

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 979
Author(s):  
Patricia Garcia-Garcia ◽  
Ricardo Reyes ◽  
José Antonio Rodriguez ◽  
Tomas Martín ◽  
Carmen Evora ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Growth Promotion ◽  
Tissue Growth ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Therapeutic Molecules ◽  
Positive Effect

Biomaterials-mediated bone formation in osteoporosis (OP) is challenging as it requires tissue growth promotion and adequate mineralization. Based on our previous findings, the development of scaffolds combining bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 10 (MMP-10) shows promise for OP management. To test our hypothesis, scaffolds containing BMP-2 + MMP-10 at variable ratios or BMP-2 + Alendronate (ALD) were prepared. Systems were characterized and tested in vitro on healthy and OP mesenchymal stem cells and in vivo bone formation was studied on healthy and OP animals. Therapeutic molecules were efficiently encapsulated into PLGA microspheres and embedded into chitosan foams. The use of PLGA (poly(lactic-co-glycolic acid)) microspheres as therapeutic molecule reservoirs allowed them to achieve an in vitro and in vivo controlled release. A beneficial effect on the alkaline phosphatase activity of non-OP cells was observed for both combinations when compared with BMP-2 alone. This effect was not detected on OP cells where all treatments promoted a similar increase in ALP activity compared with control. The in vivo results indicated a positive effect of the BMP-2 + MMP-10 combination at both of the doses tested on tissue repair for OP mice while it had the opposite effect on non-OP animals. This fact can be explained by the scaffold’s slow-release rate and degradation that could be beneficial for delayed bone regeneration conditions but had the reverse effect on healthy animals. Therefore, the development of adequate scaffolds for bone regeneration requires consideration of the tissue catabolic/anabolic balance to obtain biomaterials with degradation/release behaviors suited for the existing tissue status.

scholarly journals Clumps of Mesenchymal Stem Cells/Extracellular Matrix Complexes Generated with Xeno-Free Chondro-Inductive Medium induce Bone Regeneration via Endochondral Ossification

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1408
Author(s):  
Susumu Horikoshi ◽  
Mikihito Kajiya ◽  
Souta Motoike ◽  
Mai Yoshino ◽  
Shin Morimoto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Endochondral Ossification ◽  
Healing Process ◽  
Early Period ◽  
Cartilage Matrix

Three-dimensional clumps of mesenchymal stem cells (MSCs)/extracellular matrix (ECM) complexes (C-MSCs) can be transplanted into tissue defect site with no artificial scaffold. Importantly, most bone formation in the developing process or fracture healing proceeds via endochondral ossification. Accordingly, this present study investigated whether C-MSCs generated with chondro-inductive medium (CIM) can induce successful bone regeneration and assessed its healing process. Human bone marrow-derived MSCs were cultured with xeno-free/serum-free (XF) growth medium. To obtain C-MSCs, confluent cells that had formed on the cellular sheet were scratched using a micropipette tip and then torn off. The sheet was rolled to make a round clump of cells. The cell clumps, i.e., C-MSCs, were maintained in XF-CIM. C-MSCs generated with XF-CIM showed enlarged round cells, cartilage matrix, and hypertrophic chondrocytes genes elevation in vitro. Transplantation of C-MSCs generated with XF-CIM induced successful bone regeneration in the SCID mouse calvaria defect model. Immunofluorescence staining for human-specific vimentin demonstrated that donor human and host mouse cells cooperatively contributed the bone formation. Besides, the replacement of the cartilage matrix into bone was observed in the early period. These findings suggested that cartilaginous C-MSCs generated with XF-CIM can induce bone regeneration via endochondral ossification.

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 Nano-Hydroxyapatite as A Delivery System for Promoting Bone Regeneration In Vivo: A Systematic Review

Nanomaterials ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2569
Author(s):  
Anis Syauqina Mohd Zaffarin ◽  
Shiow-Fern Ng ◽  
Min Hwei Ng ◽  
Haniza Hassan ◽  
Ekram Alias
Keyword(s):  
Systematic Review ◽  
Bone Regeneration ◽  
Delivery System ◽  
Structural Similarity ◽  
Potential Effect ◽  
Bioactive Molecules ◽  
Bone Morphogenetic Protein 2 ◽  
Osteogenic Property ◽  
Bone Minerals

Nano-hydroxyapatite (nHA) has been widely used as an orthopedic biomaterial and vehicle for drug delivery owing to its chemical and structural similarity to bone minerals. Several studies have demonstrated that nHA based biomaterials have a potential effect for bone regeneration with very minimal to no toxicity or inflammatory response. This systematic review aims to provide an appraisal of the effectiveness of nHA as a delivery system for bone regeneration and whether the conjugation of proteins, antibiotics, or other bioactive molecules to the nHA further enhances osteogenesis in vivo. Out of 282 articles obtained from the literature search, only 14 articles met the inclusion criteria for this review. These studies showed that nHA was able to induce bone regeneration in various animal models with large or critical-sized bone defects, open fracture, or methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis. The conjugations of drugs or bioactive molecules such as bone-morphogenetic protein-2 (BMP-2), vancomycin, calcitriol, dexamethasone, and cisplatin were able to enhance the osteogenic property of nHA. Thus, nHA is a promising delivery system for a variety of compounds in promoting bone regeneration in vivo.

scholarly journals An in situ tissue engineering scaffold with growth factors combining angiogenesis and osteoimmunomodulatory functions for advanced periodontal bone regeneration

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tian Ding ◽  
Wenyan Kang ◽  
Jianhua Li ◽  
Lu Yu ◽  
Shaohua Ge
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Bone Repair ◽  
Macrophage Polarization ◽  
Tissue Engineering Scaffold ◽  
Bone Morphogenetic Protein 2 ◽  
In Situ Tissue Engineering

Abstract Background The regeneration of periodontal bone defect remains a vital clinical challenge. To date, numerous biomaterials have been applied in this field. However, the immune response and vascularity in defect areas may be key factors that are overlooked when assessing the bone regeneration outcomes of biomaterials. Among various regenerative therapies, the up-to-date strategy of in situ tissue engineering stands out, which combined scaffold with specific growth factors that could mimic endogenous regenerative processes. Results Herein, we fabricated a core/shell fibrous scaffold releasing basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) in a sequential manner and investigated its immunomodulatory and angiogenic properties during periodontal bone defect restoration. The in situ tissue engineering scaffold (iTE-scaffold) effectively promoted the angiogenesis of periodontal ligament stem cells (PDLSCs) and induced macrophage polarization into pro-healing M2 phenotype to modulate inflammation. The immunomodulatory effect of macrophages could further promote osteogenic differentiation of PDLSCs in vitro. After being implanted into the periodontal bone defect model, the iTE-scaffold presented an anti-inflammatory response, provided adequate blood supply, and eventually facilitated satisfactory periodontal bone regeneration. Conclusions Our results suggested that the iTE-scaffold exerted admirable effects on periodontal bone repair by modulating osteoimmune environment and angiogenic activity. This multifunctional scaffold holds considerable promise for periodontal regenerative medicine and offers guidance on designing functional biomaterials. Graphic Abstract

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.

Bone Regeneration Materials

2007 ◽  
Vol 342-343 ◽  
pp. 277-280 ◽  
Author(s):  
Masanori Kikuchi ◽  
M. Tanaka
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
High Strength ◽  
Autogenous Bone ◽  
High Porosity ◽  
Segmental Bone Defect ◽  
Membrane Bone ◽  
Segmental Bone ◽  
Co Precipitation ◽  
Gbr Membrane

Biomaterials Center is composed of five groups and collaborate each other to examine interdisciplinary fields of biomaterials. In the ceramics-based biomaterials research, we have been developing three novel bone regeneration materials, i.e., high-porosity hydroxyapatite (HAp) ceramics with high-strength, guided bone regeneration (GBR) membranes and bone-like nanocomposite composed of HAp and collagen. The GBR membrane composed of β-tricalcium phosphate and biodegradable copolymer of lactide, glycolide and ε-caprolactone has thermoplastic, pH auto-adjustment and enough mechanical property to protect an invasion of surrounding tissues. With the membrane, bone defect up to 20 × 10 × 10 mm3 in length in mandibles and segmental bone defect up to 20 mm in length in tibiae of beagles are regenerated without any additional bone fillers or cell transplantations. The bone-like nanocomposite is synthesized by a co-precipitation of HAp and collagen via their self-organization. The dense composite has a half to quarter mechanical strength (40 MPa) to cortical bone and the porous one demonstrates sponge-like viscoelasticity. The composites implanted into bone are incorporated into bone remodeling metabolism like as autogenous bone graft, i.e., they are resorbed by osteolasts followed by osteogenesis by osteoblasts.

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