scholarly journals Spatiotemporal regulation of angiogenesis/osteogenesis emulating natural bone healing cascade for vascularized bone formation

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xingzhi Zhou ◽  
Jiayu Chen ◽  
Hangxiang Sun ◽  
Fangqian Wang ◽  
Yikai Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Bone Healing ◽  
Umbilical Vein ◽  
Healing Process ◽  
Bone Morphogenetic Protein 2 ◽  
Growth Factor Delivery ◽  
High Concentration ◽  
Natural Bone ◽  
Vascularized Bone

AbstractEngineering approaches for growth factor delivery have been considerably advanced for tissue regeneration, yet most of them fail to provide a complex combination of signals emulating a natural healing cascade, which substantially limits their clinical successes. Herein, we aimed to emulate the natural bone healing cascades by coupling the processes of angiogenesis and osteogenesis with a hybrid dual growth factor delivery system to achieve vascularized bone formation. Basic fibroblast growth factor (bFGF) was loaded into methacrylate gelatin (GelMA) to mimic angiogenic signalling during the inflammation and soft callus phases of the bone healing process, while bone morphogenetic protein-2 (BMP-2) was bound onto mineral coated microparticles (MCM) to mimics osteogenic signalling in the hard callus and bone remodelling phases. An Initial high concentration of bFGF accompanied by a sustainable release of BMP-2 and inorganic ions was realized to orchestrate well-coupled osteogenic and angiogenic effects for bone regeneration. In vitro experiments indicated that the hybrid hydrogel markedly enhanced the formation of vasculature in human umbilical vein endothelial cells (HUVECs), as well as the osteogenic differentiation of mesenchymal stem cells (BMSCs). In vivo results confirmed the optimal osteogenic performance of our F/G-B/M hydrogel, which was primarily attributed to the FGF-induced vascularization. This research presents a facile and potent alternative for treating bone defects by emulating natural cascades of bone healing. Graphical Abstract

scholarly journals Effect of platelet-rich plasma on implant bone defects in rabbits through the FAK/PI3K/AKT signaling pathway

2019 ◽  
Vol 14 (1) ◽  
pp. 311-317
Author(s):  
Wei Liu ◽  
Ben Chen ◽  
Youyang Zheng ◽  
Yuehua Shi ◽  
Zhuojin Shi
Keyword(s):  
Growth Factor ◽  
Bone Healing ◽  
Alveolar Bone ◽  
Platelet Rich Plasma ◽  
Healing Process ◽  
Bone Defects ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Tissue Healing ◽  
Bone Healing Process

AbstractPlatelet-rich plasma (PRP) has been shown to be a beneficial growth factor for bone tissue healing and is used in implantology. The aim of this study was to investigate the effects of PRP on bone defects in rabbits. Twenty rabbits were used to establish the implant bone defect model in this study. An intrabony defect (5mm × 5mm × 3mm) was created in alveolar bone in the lower jar of each rabbit. The wound was treated with PRP. The expression of platelet-derived growth factor BB (PDGFBB) was assessed by enzyme-linked immunosorbent assay (ELISA). Focal adhesion kinase (FAK) and related phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B) levels were measured by Western blot. The results show that PRP could significantly improve the bone healing process when compared with control, and 10% PRP could markedly increase fibroblast proliferation 48-h post treatment. PDGFBB was higher in the PRP group than that in the control group. PRP treatment also could elevate the phosphorylation of FAK and PI3K/AKT, although the inhibitor of PDGFR could reverse this trend. These results suggest that PRP treatment improves the bone healing process through the FAK/PI3K/AKT pathway.

Influence of Homemade and Commercial Fibrin Sealant on Alveolar Bone Healing - an Experimental Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4110-4110
Author(s):  
Maria Elvira P. Correa ◽  
Oslei P. Almeida ◽  
Danyel Peres ◽  
Marcelo C. Alves ◽  
Fernando F. Costa ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Healing ◽  
Fibrin Sealant ◽  
Factor Xiii ◽  
Alveolar Bone ◽  
Healing Process ◽  
Control Group ◽  
Image Analysis System ◽  
New Bone Formation ◽  
Fibrin Sealants

Abstract The beneficial aspects of fibrin sealants for soft tissues are well documented, but studies of their direct influence on bone healing and their effectiveness in augmenting bone graft healing have produced conflicting results. The aim of this study was to evaluate the influence of fibrin sealants (FS) in the alveolar bone healing process during a period of up to 28 days. Seventy-five Wistar rats were submitted to a superior incisor extraction after intramuscular anesthesia (kentamine chloridrate 10% – 10mg/kg and tiazina chloridrate-5mg/kg). The rats were divided into tree different groups and the sealants were introduced into the alveolar bone. The first group (25) received human homemade fibrin glue, the second group (25) FS associated to factor XIII and aprotinin (Beriplast; Aventis-Beringher) and the third group (25) was the control. Animals were sacrificed by prolonged diethyl inhalation on days 7, 14 and 28 after surgery. Animal craniums were dissected and submitted to a decalcification, and preparated for H&E light microscopy. The morphometric study was performed by means of an interactive computerized image analysis system KS400 (Zeiss, Jena). New bone formation was carefully delimited in four different alveolar regions (apical, two middle areas and cervical) of each specimen. The data were statistically analyzed using multiple regression, ANOVA and Tukey test. Results showed that the amount of alveolar bone formation (μm) in the control group and commercial sealant was statistically similar. However, alveolus receiving homemade sealant presented less amount of new bone formation comparing to commercial sealant and control group (p=0.0034) (figure 1). The present study demonstrated that homemade fibrin sealant delays osteogenic formation. Commercial sealant did not improve alveolar repair however, the amount of new bone formation was slightly higher comparing to the control, probably due to the factor XIII present in this sealant. Figure Figure

Fracture Healing and Biomarker Expression in a Diabetic Zucker Rat Model

2014 ◽  
Vol 104 (5) ◽  
pp. 428-433 ◽  
Author(s):  
Javier La Fontaine ◽  
Nathan A. Hunt ◽  
Stacey Curry ◽  
Tyler Kearney ◽  
Daniel Jupiter ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Fracture Healing ◽  
Bone Healing ◽  
Rat Model ◽  
Healing Process ◽  
Diabetic Rats ◽  
Vascular Endothelial ◽  
Delayed Healing ◽  
Endothelial Growth Factor

Background Persons with diabetes have a higher incidence of fractures compared with persons without diabetes. However, there is little published information concerning the deleterious effect of late-stage diabetes on fracture healing. There are no studies using animal models that evaluate the effect of advanced diabetes on fracture healing. The purpose of our study was to evaluate cytokine expression, specifically macrophage inflammatory protein 1 (MIP-1) and vascular endothelial growth factor, in fracture healing in a type 2 diabetes rat model. Methods We evaluated biomarker expression after femur fracture using a rat model. The two groups consisted of 24 Zucker diabetic rats (study group) and 12 Zucker lean rats (control group). An independent reviewer was used to assess delayed union. We evaluated serum samples 2, 4, 7, and 14 days after surgery for MIP-1, vascular endothelial growth factor, leptin, and other cytokine levels. Results At 3 weeks, Kaplan-Meier estimates showed that 45.8% of femur fractures in Zucker diabetic rats had healed, whereas 81.8% of those in Zucker lean rats had healed (P = .02). A logistic regression model to predict fast healing that included the three cytokines and diabetes status showed that the only factor achieving significance was MIP-1α. Vascular endothelial growth factor was the only biomarker to show significance compared with delayed healing. Conclusions These results confirm significant differences in biomarker expression between diabetic and nondiabetic rats during bone healing. The key factors for bone healing may appear early in the healing process, whereas differences in diabetes versus nondiabetes are seen later in the healing process. Increased levels of MIP-1α were associated with the likelihood of delayed healing.

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 Effects of Eleutherococcus Extract Mixture on Endochondral Bone Formation in Rats

2019 ◽  
Vol 20 (5) ◽  
pp. 1253 ◽  
Author(s):  
Donghun Lee ◽  
Sung Lee ◽  
Namhoon Cho ◽  
Young-Sik Kim ◽  
Jungbin Song ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Formation ◽  
Female Adolescent ◽  
Bone Morphogenetic Protein 2 ◽  
Endochondral Bone Formation ◽  
Insulin Like Growth Factor ◽  
Endochondral Bone ◽  
Fluorescent Band ◽  
Traditional Medicines

Eleutherococcus extract mixture (EEM) is an herbal mixture of dried stem of Eleutherococcus sessiliflorus and germinated barley, which has been highly effective, in previous screening and among the traditional medicines to tonify innate qi and acquired qi, respectively. In this study, we investigate the effects of EEM on endochondral bone formation. Female adolescent rats were given EEM, growth hormone or vehicle for 10 days. Tetracycline was intraperitoneally injected to light the fluorescent band 72 h before sacrifice to determine endochondral bone formation. In order to evaluate endocrine or paracrine/autocrine mechanisms, expressions of insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), or bone morphogenetic protein 2 (BMP2) were evaluated after EEM administration in liver or growth plate (GP). EEM oral administration significantly increased endochondral bone formation and proliferative and hypertrophic zonal heights of tibial GP. EEM also upregulated hepatic IGF1 and IGFBP3 mRNA expressions, and IGF1 and BMP2 expressions in GP. Taken together, EEM increases endochondral bone formation through stimulating proliferation and hypertrophy with upregulation of hepatic IGF1 and IGFBP3 expressions. Considering immunohistochemical studies, the effect of EEM may be due to increased local IGF1 and BMP2 expression in GP, which may be considered growth hormone (GH)-dependent endocrine and autocrine/paracrine pathways.

scholarly journals Cigarette smoke inhalation influences bone healing of post-extraction tooth socket: a histometric study in rats

2012 ◽  
Vol 23 (3) ◽  
pp. 228-234 ◽  
Author(s):  
Ana Paula Oliveira Giorgetti ◽  
João Batista César Neto ◽  
Márcio Zaffalon Casati ◽  
Enílson Antonio Sallum ◽  
Francisco Humberto Nociti Júnior
Keyword(s):  
Bone Formation ◽  
Cigarette Smoke ◽  
Bone Healing ◽  
Healing Process ◽  
Test Group ◽  
Smoke Inhalation ◽  
Control Group ◽  
Mineralized Tissue ◽  
Male Wistar Rats ◽  
Socket Healing

The aim of this study was to evaluate, histometrically, the bone healing of the molar extraction socket just after cigarette smoke inhalation (CSI). Forty male Wistar rats were randomly assigned to a test group (animals exposed to CSI, starting 3 days before teeth extraction and maintained until sacrifice; n=20) and a control group (animals never exposed to CSI; n=20). Second mandibular molars were bilaterally extracted and the animals (n=5/group/period) were sacrificed at 3, 7, 10 and 14 days after surgery. Digital images were analyzed according to the following histometric parameters: osteoid tissue (OT), remaining area (RA), mineralized tissue (MT) and non-mineralized tissue (NMT) in the molar socket. Intergroup analysis showed no significant differences at day 3 (p>0.05) for all parameters. On the 7th day, CSI affected negatively (p<0.05) bone formation with respect to NMT and RA (MT: 36%, NMT: 53%, RA: 12%; and MT: 39%, NMT: 29%, RA: 32%, for the control and test groups, respectively). In contrast, no statistically significant differences (p>0.05) were found at days 10 and 14. It may be concluded that CSI may affect socket healing from the early events involved in the healing process, which may be critical for the amount and quality of new-bone formation in smokers.

scholarly journals The Effects of Platelet-Derived Growth Factor-BB on Bone Marrow Stromal Cell-Mediated Vascularized Bone Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Maolin Zhang ◽  
Wenwen Yu ◽  
Kunimichi Niibe ◽  
Wenjie Zhang ◽  
Hiroshi Egusa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Bone Regeneration ◽  
Lentiviral Vector ◽  
Umbilical Vein ◽  
Adipogenic Differentiation ◽  
Platelet Derived Growth Factor ◽  
Extracellular Signal ◽  
Rat Calvarial Defect ◽  
Vascularized Bone

Regenerative medicine for bone tissue mainly depends on efficient recruitment of endogenous or transplanted stem cells to guide bone regeneration. Platelet-derived growth factor (PDGF) is a functional factor that has been widely used in tissue regeneration and repair. However, the short half-life of PDGF limits its efficacy, and the mechanism by which PDGF regulates stem cell-based bone regeneration still needs to be elucidated. In this study, we established genetically modified PDGF-B-overexpressing bone marrow stromal cells (BMSCs) using a lentiviral vector and then explored the mechanism by which PDGF-BB regulates BMSC-based vascularized bone regeneration. Our results demonstrated that PDGF-BB increased osteogenic differentiation but inhibited adipogenic differentiation of BMSCs via the extracellular signal-related kinase 1/2 (ERK1/2) signaling pathway. In addition, secreted PDGF-BB significantly enhanced human umbilical vein endothelial cell (HUVEC) migration and angiogenesis via the phosphatidylinositol 3 kinase (PI3K)/AKT and ERK1/2 signaling pathways. We evaluated the effect of PDGF-B-modified BMSCs on bone regeneration using a critical-sized rat calvarial defect model. Radiography, micro-CT, and histological analyses revealed that PDGF-BB overexpression improved BMSC-mediated angiogenesis and osteogenesis during bone regeneration. These results suggest that PDGF-BB facilitates BMSC-based bone regeneration by enhancing the osteogenic and angiogenic abilities of BMSCs.

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