scholarly journals Cigarette smoke inhalation impairs angiogenesis in early bone healing processes and delays fracture union

2020 ◽  
Vol 9 (3) ◽  
pp. 99-107 ◽  
Author(s):  
Chao-Jui Chang ◽  
I-Ming Jou ◽  
Tung-Tai Wu ◽  
Fong-Chin Su ◽  
Ta-Wei Tai

Aims Cigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing. Methods We established a custom-made chamber with airflow for rats to inhale cigarette smoke continuously, and tested our hypothesis using a femoral osteotomy model, radiograph and microCT imaging, and various biomechanical and biological tests. Results In the smoking group, Western blot analysis and immunohistochemical staining revealed less expression of vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF). The smoking group also had a lower microvessel density than the control group. Image and biochemical analysis also demonstrated delayed bone healing. Conclusion Cigarette smoke inhalation was associated with decreased expression of angiogenic markers in the early bone healing phase and with impaired bone healing. Cite this article: Bone Joint Res. 2020;9(3):99–107.

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

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.


Author(s):  
Hanjong Kim ◽  
Changwan Han ◽  
Otgonbayar Maidar ◽  
Sang-Soo Lee ◽  
Seonghun Park

Kaempferol is a typical flavonol-type flavonoid and has a protective effect on postmenopausal bone loss, and previous studies have reported that kaempferol treated groups show an increase in the callus size and bone mineral density as well as improvement in biomechanical behaviors in comparison with untreated control groups in the bone healing process. The present study aims at investigating the effect of kaempferol treatments on fractured murine tibia, by measuring kaempferol dose-dependent mechanical properties in the bone healing process of murine tibia fracture models. A stabilized fracture was generated at tibia by minor modification of the Hiltunen method for 8 weeks old ICR mice weighting 29.0 ∼ 30.5 g. Experimental mice were divided into 4 groups. Kaempferol of 0.2, 1.0, 5.0 mg/kg (body weight) with 20 % ethanol was administered to 3 groups and the remaining one group was only treated with 20 % ethanol as a control group. Three-point bending fracture tests were conducted to measure the mechanical properties (fracture load, fracture energy, stiffness) of murine tibiae at non-fractured regions near fracture sites 21 days after kaempferol treatments, via a custom-made biomechanical testing system (BTS, KST Co., Korea). The 5.0 mg/kg kaempferol treated group shows higher fracture load (20.54 ±5.04 N) than the control group (17.82 ±5.94 N). Fracture energy, total energy applied to tibia up to bone fracture, exhibited no significant differences between the control group and any of the kampferol treated groups, although both the 1.0 mg/kg kaempferol treated and control groups showed a little higher fracture energy than the 0.2 and 5.0 mg/kg kaempferol treated groups. Bone stiffness also did not show statistically significant differences between the control group and any of the kaempferol treated groups, with the highest stiffness value observed in the 1.0 mg/kg kaempferol treated group.


Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 691
Author(s):  
Jan Barcik ◽  
Devakara R. Epari

The impact of the local mechanical environment in the fracture gap on the bone healing process has been extensively investigated. Whilst it is widely accepted that mechanical stimulation is integral to callus formation and secondary bone healing, treatment strategies that aim to harness that potential are rare. In fact, the current clinical practice with an initially partial or non-weight-bearing approach appears to contradict the findings from animal experiments that early mechanical stimulation is critical. Therefore, we posed the question as to whether optimizing the mechanical environment over the course of healing can deliver a clinically significant reduction in fracture healing time. In reviewing the evidence from pre-clinical studies that investigate the influence of mechanics on bone healing, we formulate a hypothesis for the stimulation protocol which has the potential to shorten healing time. The protocol involves confining stimulation predominantly to the proliferative phase of healing and including adequate rest periods between applications of stimulation.


Membranes ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 124
Author(s):  
Ana Paula Farnezi Bassi ◽  
Vinícius Ferreira Bizelli ◽  
Tamires Mello Francatti ◽  
Ana Carulina Rezende de Moares Ferreira ◽  
Járede Carvalho Pereira ◽  
...  

Biomaterials for use in guided bone regeneration (GBR) are constantly being investigated and developed to improve clinical outcomes. The present study aimed to comparatively evaluate the biological performance of different membranes during the bone healing process of 8 mm critical defects in rat calvaria in order to assess their influence on the quality of the newly formed bone. Seventy-two adult male rats were divided into three experimental groups (n = 24) based on the membranes used: the CG—membrane-free control group (only blood clot, negative control), BG—porcine collagen membrane group (Bio-Guide®, positive control), and the PCL—polycaprolactone (enriched with 5% hydroxyapatite) membrane group (experimental group). Histological and histometric analyses were performed at 7, 15, 30, and 60 days postoperatively. The quantitative data were analyzed by two-way ANOVA and Tukey’s test (p < 0.05). At 7 and 15 days, the inflammatory responses in the BG and PCL groups were significantly different (p < 0.05). The PCL group, at 15 days, showed a large area of newly formed bone. At 30 and 60 days postoperatively, the PCL and BG groups exhibited similar bone healing, including some specimens showing complete closure of the critical defect (p = 0.799). Thus, the PCL membrane was biocompatible, and has the potential to help with GBR procedures.


2018 ◽  
Vol 62 (3) ◽  
pp. 385-394 ◽  
Author(s):  
Hadi Eftekhari ◽  
Alireza Jahandideh ◽  
Ahmad Asghari ◽  
Abolfazl Akbarzadeh ◽  
Saeed Hesaraki

AbstractIntroductionIn recent years, the use of bone scaffolds as bone tissue substitutes, especially the use of such as hydroxyapatite and tricalcium phosphate, has been very popular. Today, the use of modern engineering techniques and advances in nanotechnology have expanded the use of nanomaterials as bone scaffolds for bone tissue applications.Material and MethodsThis study was performed on 60 adult male New Zealand rabbits divided into four experimental groups: the control group without any treatment, the second group receiving hydroxyapatite, the third group treated with β-tricalcium phosphate, and the fourth group receiving nanocomposite polycaprolactone (PCL) scaffold. In a surgical procedure, a defect 6 mm in diameter was made in a hind limb femur. Four indexes were used to assess histopathology, which were union index, spongiosa index, cortex index, and bone marrow.ResultsThe results showed that nanocomposite PCL and control groups always had the respective highest and lowest values among all the groups at all time intervals. The histopathological assessment demonstrated that the quantity of newly formed lamellar bone in the nanocomposite PCL group was higher than in other groups.ConclusionAll these data suggest that PCL had positive effects on the bone healing process, which could have great potential in tissue engineering and clinical applications.


2019 ◽  
Vol 14 (1) ◽  
pp. 311-317
Author(s):  
Wei Liu ◽  
Ben Chen ◽  
Youyang Zheng ◽  
Yuehua Shi ◽  
Zhuojin Shi

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.


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 ◽  
...  

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


2014 ◽  
Vol 104 (5) ◽  
pp. 428-433 ◽  
Author(s):  
Javier La Fontaine ◽  
Nathan A. Hunt ◽  
Stacey Curry ◽  
Tyler Kearney ◽  
Daniel Jupiter ◽  
...  

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.


2019 ◽  
Vol 26 (2) ◽  
pp. 164-169
Author(s):  
Naira Helena Bohrer Scherer ◽  
Antonio Marcos Vargas da Silva ◽  
Jessié Gutierres ◽  
Carolina Fantinel Veloso ◽  
Carlos Eduardo Pinfildi ◽  
...  

ABSTRACT Nicotine delays the healing process and increases the levels of myeloperoxidase (MPO), an enzyme that plays a key role in the production of reactive oxygen species during the inflammatory process. Laser Photobiomodulation (PBM) is one of the most used electrophysical agents in the treatment of the calcaneal tendon, however, its effects on MPO activity need to be further elucidated. This study aimed to evaluate the effects of laser PBM on MPO activity after inflicting an injury to the calcaneal tendon of rats exposed to cigarette smoke. Thirty-four male Wistar rats with 90 days of age were used. After 14 days of exposure to cigarette smoke, the animals were divided into three experimental groups: control group (CG, n=12), not submitted to injury or treatment; sham group (ShG, n=10), submitted to partial calcaneal tendon injury and laser PBM simulation; and laser PBM group (PBMG, n=12), submitted to partial calcaneal tendon lesion and treated with laser PBM within the first minute after injury. PBM decreased MPO activity levels in PBMG compared to ShG (CG: 1.38±0.69pg/ml; ShG: 3.78±1.09pg/ml; PBMG: 2.58±0.93pg/ml; p<0.005). In conclusion, applying laser PBM immediately after inflicting damage to the calcaneal tendon attenuates acute inflammatory activity in rats exposed to cigarette smoke.


Polymers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 436 ◽  
Author(s):  
Yu-Min Huang ◽  
Yi-Cheng Lin ◽  
Chih-Yu Chen ◽  
Yueh-Ying Hsieh ◽  
Chen-Kun Liaw ◽  
...  

Healing of an anterior cruciate ligament graft in bone tunnel yields weaker fibrous scar tissue, which may prolong an already prolonged healing process within the tendon–bone interface. In this study, gelatin molecules were added to thermosensitive chitosan/β-glycerol phosphate disodium salt hydrogels to form chitosan/gelatin/β-glycerol phosphate (C/G/GP) hydrogels, which were applied to 0.1 mg/mL collagenase carrier in the tendon–bone junction. New Zealand white rabbit’s long digital extensor tendon was detached and translated into a 2.5-mm diameter tibial plateau tunnel. Thirty-six rabbits underwent bilateral surgery and hydrogel injection treatment with and without collagenase. Histological analyses revealed early healing and more bone formation at the tendon–bone interface after collagenase partial digestion. The area of metachromasia significantly increased in both 4-week and 8-week groups after collagenase treatment (p < 0.01). Micro computed tomography showed a significant increase in total bone volume and bone volume/tissue volume in the 8 weeks after collagenase treatment, compared with the control group. Load-to-failure was significantly higher in the treated group at 8 weeks (23.8 ± 8.13 N vs 14.3 ± 3.9 N; p = 0.008). Treatment with collagenase digestion resulted in a 66% increase in pull-out strength. In conclusion, injection of C/G/GP hydrogel with collagenase improves tendon-to-bone healing in a rabbit model.


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