Postoperative administration of the acetylcholinesterase inhibitor, donepezil, interferes with bone healing and implant osseointegration in a rat model

Donepezil is an acetylcholinesterase inhibitor commonly used to treat mild to moderate Alzheimer’s disease. Its use has been associated with increased bone mass in humans and animals. However, the effect of postoperative administration of donepezil on bone healing remains unknown. Therefore, this study aimed to assess the impact of postoperative injection of donepezil on bone healing, titanium-implant osseointegration, and soft tissue healing. Twenty-two Sprague-Dawley rats were randomly assigned to receive a daily dose of either donepezil (0.6 mg/kg) or saline as a control. In each rat, a uni-cortical defect was created in the right tibia metaphysis and a custom-made titanium implant was placed in the left tibiae. After two weeks, rats were euthanized, and their bones were analysed by Micro-CT and histology. The healing of bone defect and implant osseointegration in the rats treated with donepezil were significantly reduced compared to the saline-treated rats. Histomorphometric analysis showed lower immune cell infiltration in bone defects treated with donepezil compared to the saline-treated defects. On the other hand, the healing time of soft tissue wounds was significantly shorter in donepezil-treated rats compared to the controls. In conclusion, short-term administration of donepezil hinders bone healing whereas enhancing soft tissue healing

Differences in platelet-rich plasma composition influence bone healing

Aim: Platelet-rich plasma (PRP) is an autologous blood-derived material that has been used to enhance bone regeneration. Clinical studies, however, reported inconsistent outcomes. This study aimed to assess the effect of changes in leucocyte and PRP (L-PRP) composition on bone defect healing. Materials and Methods: L-PRPs were prepared using different centrifugation methods and their regenerative potential was assessed in an in-vivo rat model. Bilateral critical-size tibial bone defects were created and filled with single-spin L-PRP, double-spin L-PRP, or filtered L-PRP. Empty defects and defects treated with collagen scaffolds served as controls. Rats were euthanized after 2 weeks, and their tibias were collected and analysed using micro-CT and histology. Results: Double-spin L-PRP contained higher concentrations of platelets than singlespin L-PRP and filtered L-PRP. Filtration of single-spin L-PRP resulted in lower concentrations of minerals and metabolites. In vivo, double-spin L-PRP improved bone healing by significantly reducing the size of bone defects (1.08 ± 0.2 mm3 ) compared to single-spin L-PRP (1.42 ± 0.27 mm3 ) or filtered L-PRP (1.38 ± 0.28 mm3 ). There were fewer mast cells, lymphocytes, and macrophages in defects treated with double-spin L-PRP than in those treated with single-spin or filtered L-PRP. Conclusion: The preparation method of L-PRP affects their composition and potential to regenerate bone

Assessment of alveolar bone marrow fat content using 15 T MRI

Objectives: Bone marrow fat is inversely correlated with bone mineral density. The aim of this study is to present a method to quantify alveolar bone marrow fat content using a 15 T magnetic resonance imaging (MRI) scanner.Study design: A 15 T MRI scanner with a 13-mm inner diameter loop-gap radiofrequency coil was used to scan seven 3-mm diameter alveolar bone biopsy specimens. A 3-D gradient-echo relaxation time (T1)-weighted pulse sequence was chosen to obtain images. All images were obtained with a voxel size (58 µm3) sufficient to resolve trabecular spaces. Automated volume of the bone marrow fat content and derived bone volume fraction (BV/TV) were calculated. Results were compared with actual BV/TV obtained from micro-computed tomography (CT) scans.Results: Mean fat tissue volume was 20.1 ± 11%. There was a significantly strong inverse correlation between fat tissue volume and BV/TV (r = -0.68; P = .045). Furthermore, there was a strong agreement between BV/TV derived from MRI and obtained with micro-CT (interclass correlation coefficient = 0.92; P = .001).Conclusions: Bone marrow fat of small alveolar bone biopsy specimens can be quantified with sufficient spatial resolution using an ultra-high-field MRI scanner and a T1-weighted pulse sequence.peer-reviewe

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

The effect of selective serotonin reuptake inhibitors on bone healing and titanium implant osseointegration

For the past 30 years, titanium implants have been used routinely to treat partial and complete dental edentulism. The clinical success of titanium implants relies on osseointegration, a process similar to bone healing. Successful osseointegration of titanium implant requires normal functioning of the biological events that occur during bone healing. Therefore, any factor that alters bone healing will jeopardise the success of titanium implant and might cause peri-implant complication or premature implant loss.Many people worldwide are exposed to long-term use of systemic medications. Many of these medications are known to interfere with bone accrual. Yet, little is known about the potential effect of these medications on titanium implant osseointegration. Selective Serotonin Re-uptake Inhibitors (SSRIs) are a group of anti-depressant drugs taken by more than 350 million patients worldwide; they inhibit the re-uptake of serotonin in the presynaptic clefts in the brain, giving the sensation of good mood. These drugs have been shown to decrease bone mineral density and increase the incidence of bone fracture. However, the potential effect of these drugs on bone healing and implant osseointegration has not been investigated yet. This thesis includes an in vivo study conducted to investigate the effect of SSRIs on bone healing and implant osseointegration. In this in vivo study, we have shown that SSRIs hinder bone healing and implant osseointegtration probably by altering the number and function of osteoblasts and osteoclasts, Moreover, we have demonstrated that SSRIs alter the immune response, causing changes in serum levels of many immunocytokines (i.e. IL-1β, INF-γ) involved in the inflammatory stage of the bone healing process. In this study, we provided the first scientific evidence on the negative effects of SSRIs on titanium implant osseointegration and bone healing. Consequently, SSRIs treatment should be taken into account by clinician upon patient selection, treatment planning, and maintenance for bone surgery and implant therapy.Au cours des 30 dernières années, les implants en titane ont été utilisés couramment pour traiter l'édentorisme dentaire partiel et complet. Le succès clinique des implants de titane repose sur l'ostéointégration, un processus similiare à la guérison osseuse. L'ostéointégration réussie de l'implant de titane nécessite un fonctionnement normal des événements biologiques qui se produisent pendant la guérison osseuse. Par conséquent, tout facteur qui modifie la guérison osseuse compromettra le succès de l'implant de titane et pourrait entraîner une complication péri-implantaire ou une perte prématurée de l'implant.Beaucoup de personnes dans le monde sont exposées à long terme des médicaments systémiques. Il est convenu dans les littérature que beaucoup de ces médicaments interfèrent avec l'accumulation minérale dans les os. Pourtant, on connaît peu l'effet potentiel de ces médicaments sur l'ostéointégration des implant de titane. Les inhibiteurs sélectifs de réabsorption de la sérotonine (ISRS) forment un groupe de médicaments antidépresseurs pris par plus de 350 millions de patients à travers le monde; Ils inhibent la ré-absorption de la sérotonine dans les fissures présynaptiques dans le cerveau, ce qui donne une sensation de bonne humeur. On a montré que ces médicaments diminuent la densité minérale osseuse et augmentent l'incidence de fractueres osseuses. Cependant, l'effet potentiel de ces médicaments sur la guérison osseuse et l'ostéointégration des implants n'a pas encore été étudié. Cette thèse comprend une étude in vivo menée pour étudier l'effet des ISRS sur la guérison osseuse et l'ostéointégration des implant. Dans cette étude in vivo, nous avons montré que les ISRS entravent la cicatrisation osseuse et l'osseointération des implants probablement en modifiant le nombre et la fonction des ostéoblastes et des ostéoclastes. En outre, nous avons démontré que les ISRS altèrent la réponse immunitaire, entraînant des changements dans les taux sériques de nombreuses immunocytokines (c'est à dire. IL-1β, INF-γ) impliqués dans le stade inflammatoire du processus de guérison des os. Dans cette étude, nous avons fourni les premières preuves scientifiques sur les effets négatifs des ISRS sur l'ostéo-intégration de titane et la cicatrisation osseuse. Par conséquent, le traitment des ISRS doit être pris en compte par le clinicien lors de la sélection des patients du clinicien, la planification du traitement et la maintenance de la chirurgie osseuse et de la thérapie implantaire

2D magnesium phosphate resorbable coating to enhance cell adhesion on titanium surfaces

Titanium and its alloys are essential metals for orthopedic implant manufacturing due to their exceptional mechanical properties and biocompatibility, used extensively for treating various orthopedic conditions. However, Titanium (Ti) implants have a disadvantage due to lack of bioactivity, potentially affecting osseointegration and osteoconductive capabilities, and may take several months to integrate with bone tissue. In this work, we prepared a layer of 2D magnesium phosphate (MgPi) coating on the surface of titanium surfaces via the spin-coating technique. Various techniques were used to study the phase composition of the coatings, including FTIR, Raman spectroscopy, NMR, and XRD analysis. Morphology and chemical analysis were performed using Atomic force microscopy and SEM/EDX. Nano-scratch test and water contact angle measurements were used to measure adhesion strength and wettability. In addition, in vitro cell assays were used to assess cell adhesion and viability to determine how the MC3T3-E1 osteoblast-like cells reacted to the different treated Ti substrates. AFM results showed that the surface roughness became lower after coatings. MgPi-coated samples showed higher hydrophilicity, protein adsorption, and cell viability than uncoated samples. The nano-scratch test showed that the MgPi coating showed better adherence to chemically and thermally treated samples compared to untreated samples. The deposited MgPi coating has good adhesion to the Ti-substrates. Most significantly, compared to uncoated control (Ti) (p < 0.005) and chemically treated coated samples CT-MgPi (p < 0.005), MC3T3-E1 cell proliferation was significantly increased on thermochemical coated surfaces. These findings point to resorbable two-dimensional MgPi coatings as a potential candidate for promoting Ti implant osseointegration

Postoperative Administration of the Acetylcholinesterase Inhibitor, Donepezil, Interferes with Bone Healing and Implant Osseointegration in a Rat Model

International audienceDonepezil is an acetylcholinesterase inhibitor commonly used to treat mild to moderate Alzheimer's disease. Its use has been associated with increased bone mass in humans and animals. However, the effect of postoperative administration of donepezil on bone healing remains unknown. Therefore, this study aimed to assess the impact of postoperative injection of donepezil on bone healing, titanium-implant osseointegration, and soft tissue healing. Twenty-two Sprague-Dawley rats were randomly assigned to receive a daily dose of either donepezil (0.6 mg/kg) or saline as a control. In each rat, a uni-cortical defect was created in the right tibia metaphysis and a custom-made titanium implant was placed in the left tibiae. After two weeks, rats were euthanized, and their bones were analysed by Micro-CT and histology. The healing of bone defect and implant osseointegration in the rats treated with donepezil were significantly reduced compared to the saline-treated rats. Histomorphometric analysis showed lower immune cell infiltration in bone defects treated with donepezil compared to the saline-treated defects. On the other hand, the healing time of soft tissue wounds was significantly shorter in donepezil-treated rats compared to the controls. In conclusion, short-term administration of donepezil hinders bone healing whereas enhancing soft tissue healing

Differences in platelet‐rich plasma composition influence bone healing

Aim: Platelet-rich plasma (PRP) is an autologous blood-derived material that has been used to enhance bone regeneration. Clinical studies, however, reported inconsistent outcomes. This study aimed to assess the effect of changes in leucocyte and PRP (L-PRP) composition on bone defect healing. Materials and Methods: L-PRPs were prepared using different centrifugation methods and their regenerative potential was assessed in an in-vivo rat model. Bilateral critical-size tibial bone defects were created and filled with single-spin L-PRP, double-spin L-PRP, or filtered L-PRP. Empty defects and defects treated with collagen scaffolds served as controls. Rats were euthanized after 2 weeks, and their tibias were collected and analysed using micro-CT and histology. Results: Double-spin L-PRP contained higher concentrations of platelets than singlespin L-PRP and filtered L-PRP. Filtration of single-spin L-PRP resulted in lower concentrations of minerals and metabolites. In vivo, double-spin L-PRP improved bone healing by significantly reducing the size of bone defects (1.08 ± 0.2 mm3) compared to single-spin L-PRP (1.42 ± 0.27 mm3) or filtered L-PRP (1.38 ± 0.28 mm3). There were fewer mast cells, lymphocytes, and macrophages in defects treated with double-spin L-PRP than in those treated with single-spin or filtered L-PRP. Conclusion: The preparation method of L-PRP affects their composition and potential to regenerate bone.Depto. de Especialidades Clínicas OdontológicasFac. de OdontologíaTRUEpu