Cite this article:
Aims. Successful cell therapy in hip osteonecrosis (ON) may help to avoid ON progression or total hip arthroplasty (THA), but the achieved
Aims. The use of 3D-printed titanium implant (DT) can effectively guide
Objectives. This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling. Methods. A systematic search was performed in Pubmed, followed by a two-step selection process. We included in vivo original studies on Sr-containing biomaterials used for bone support or regeneration, comparing at least two groups that only differ in Sr addition in the experimental group. Results. A total of 572 references were retrieved and 27 were included. Animal models were used in 26 articles, and one article described a human study. Osteoporotic models were included in 11 papers. All articles showed similar or increased effect of Sr in bone formation and/or regeneration, in both healthy and osteoporotic models. No study found a decreased effect. Adverse effects were assessed in 17 articles, 13 on local and four on systemic adverse effects. From these, only one reported a systemic impact from Sr addition. Data on gene and/or protein expression were available from seven studies. Conclusions. This review showed the safety and effectiveness of Sr-enriched biomaterials for stimulating bone formation and remodelling in animal models. The effect seems to increase over time and is impacted by the concentration used. However, included studies present a wide range of study methods. Future work should focus on consistent models and guidelines when developing a future clinical application of this element. Cite this article: N. Neves, D. Linhares, G. Costa, C. C. Ribeiro, M. A. Barbosa. In vivo and clinical application of strontium-enriched biomaterials for
Aims. To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and
Introduction: There is a need for new non-invasive, predictable and quantifiable techniques to assess the process of fracture healing and remodelling in bone. There are several methods to monitor the bone healing in-vivo. But these methods either fail as quantitative predictors of the healing process (X-ray) or exhibit complicated and expensive measurement principles. Some known in-vivo stiffness measurement methods have several disadvantages including the risk of bone malalignment. Therefore we compared ex-vivo torsional strength of bone with in-vivo torsional stiffness under minimal load in two animal model of distraction osteogenesis. Additionally the device was tested in an ex-vivo model. Methods: An external fixator was combined with a rotating double half-ring. The measurement device was fixed to the half-ring during measurements. It was equipped with a linear variable differential transducer, a load cell, and a stepper motor. During measurements the two parts of the half-ring were rotated against each other and the load and displacement were recorded. The slope coefficient after performing a linear regression between data points of moment and displacement curve was defined as stiffness. Afterwards all models were tested in a material testing system as gold standard. This was tested in an in-vivo animal study of tibial distraction (minipigs time of consolidation 10 days/sheeps time of consolidation 50 days). Results: Between in-vivo initial torsional stiffness and torsional strength in minipigs we found a highly significant (p=0.001) coefficient of determination of 0.82, but we found only a poor correlation (p>
0.05) in sheeps. However, the results of the ex-vivo model showed a high precision and accuracy. Discussion: The results of this study suggest that the
The purpose of this study was to evaluate A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted
subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm
PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight
and 12 weeks post-implantation were compared with control (Sham)
and PLAGA (five rats per group/point in time). Rats were observed
for signs of morbidity, overt toxicity, weight gain and food consumption,
while haematology, urinalysis and histopathology were completed
when the animals were killed.Objectives
Methods
To prevent the reported side effects of rhBMP-2, an important cytokine with bone forming capacity, the sustained release of rhBMP-2 is highly important. Synthetic copolymer polylactic acid-polyethylene glycol (PLA-PEG) is already shown to be a good carrier for rhBMP-2. The nano-sized hydroxyapatite (nHAp) is mentioned to be superior to conventional hydroxyapatite due to its decreased particle size which increases the surface area, so protein-cell adhesion and mechanical properties concomitantly. In the literature no study is reported with PLA-PEG / rhBMP-2/ nHAp for
Healing in cancellous metaphyseal bone might be different from
midshaft fracture healing due to different access to mesenchymal
stem cells, and because metaphyseal bone often heals without a cartilaginous
phase. Inflammation plays an important role in the healing of a
shaft fracture, but if metaphyseal injury is different, it is important
to clarify if the role of inflammation is also different. The biology
of fracture healing is also influenced by the degree of mechanical
stability. It is unclear if inflammation interacts with stability-related
factors. We investigated the role of inflammation in three different models:
a metaphyseal screw pull-out, a shaft fracture with unstable nailing
(IM-nail) and a stable external fixation (ExFix) model. For each,
half of the animals received dexamethasone to reduce inflammation,
and half received control injections. Mechanical and morphometric evaluation
was used.Objectives
Methods
Cancellous and cortical bone used as a delivery vehicle for antibiotics. Recent studies with cancellous bone as an antibiotic carrier in vitro and in vivo showed high initial peak concentrations of antibiotics in the surrounding medium. However, high concentrations of antibiotics can substantially reduce osteoblast replication and even cause cell death. To determine whether impregnation with gentamycine impair the incorporation of bone allografts, as compared to allografts without antibiotic.Introduction
Objectives
Growth factors produced by inflammatory cells and mesenchymal progenitors are required for proper
Anatomically, bone consists of building blocks called osteons, which in turn comprise a central canal that contains nerves and blood vessels. This indicates that bone is a highly innervated and vascularized tissue. The function of vascularization in bone (development) is well-established: providing oxygen and nutrients that are necessary for the formation, maintenance, and healing. As a result, in the field of bone tissue engineering many research efforts take vascularization into account, focusing on engineering vascularized bone. In contrast, while bone anatomy indicates that the role of innervation in bone is equally important, the role of innervation in bone tissue engineering has often been disregarded. For many years, the role of innervation in bone was mostly clear in physiology, where innervation of a skeleton is responsible for sensing pain and other sensory stimuli. Unraveling its role on a cellular level is far more complex, yet more recent research efforts have unveiled that innervation has an influence on osteoblast and osteoclast activity. Such innervation activities have an important role in the regulation of bone homeostasis, stimulating bone formation and inhibiting resorption. Furthermore, due to their anatomical proximity, skeletal nerves and blood vessels interact and influence each other, which is also demonstrated by pathways cross-over and joint responses to stimuli. Besides those closely connected sytems, the immune system plays also a pivotal role in
We found that adipose stem cells are poorly differentiated into bone and that their ability to differentiate into bone varies from cell line to cell line. The osteogenic differentiation ability of the adipose stem cell lines was distinguished through Alzarin Red Staining, and the cell lines that performed well and those that did not were subjected to RNA-seq analysis. The selected gene GSTT1 (glutathione S-transferase theta-1) gene is a member of a protein superfamily that catalyzes the conjugation of reduced glutathione to a variety of hydrophilic and hydrophobic compounds. The purpose of this study is to treat avascular necrosis and bone defect by improving
Mesenchymal stem cells (MSC) have been used for
Introduction and Objective. Alveolar bone resorption following tooth extraction or periodontal disease compromises the bone volume required to ensure the stability of an implant. Guided
To design slow resorption patient-specific bone graft whose properties of
Aims. Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for
Bone tissue is known to possess an intrinsic regeneration potential. However, in cases of major injury, trauma, and disease, bone loss is present, and the regeneration potential of the tissue is often impaired. The process of
The ability of the body to constantly maintain metabolism homeostasis while fulling the heightened energy and macromolecule demand is crucial to ensure successful tissue healing outcomes. Studies investigating the local metabolic environment during healing are scarce to date. Here, using Type 2 Diabetes (T2D) as a study model, we investigate the impact of metabolism dysregulation on scaffold-guided large-volume
Bone defects require implantable graft substitutes, especially porous and biodegradable biomaterial for tissue regeneration. The aim of this study was to fabricate and assess a 3D-printed biodegradable hydroxyapatite/calcium carbonate scaffold for
Stem cell therapy is an effective means to address the repair of large segmental bone defects. However, the intense inflammatory response triggered by the implants severely impairs stem cell differentiation and tissue regeneration. High-dose transforming growth factor β1 (TGF-β1), the most locally expressed cytokine in implants, inhibits osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and promotes tissue fibrosis, severely compromising the efficacy of stem cell therapy. Small molecule inhibitors of TGF-β1 can be used to ameliorate the osteogenic disorders caused by high concentrations of TGF-β1, but systemic inhibition of TGF-β1 function will cause strong adverse effects. How to find safe and reliable molecular targets to antagonize TGF-β1 remains to be elucidated. Orphan nuclear receptor Nr4a1, an endogenous inhibitory molecule of TGF-β1, suppresses tissue fibrosis, but its role in BMSC osteogenesis is unclear. We found that TGF-β1 inhibited Nr4a1 expression through HDAC4. Overexpression of Nr4a1 in BMSCs reversed osteogenic differentiation inhibited by high levels of TGF- β1. Mechanistically, RNA sequencing showed that Nr4a1 activated the ECM-receptor interaction and Hippo signaling pathway, which in turn promoted BMSC osteogenesis. In bone defect repair and fracture healing models, transplantation of Nr4a1-overexpressing BMSCs into C57BL/6J mice or treatment with the Nr4a1 agonist Csn-B significantly ameliorated inflammation-induced
Although bone morphogenetic protein 2 (BMP-2) has been FDA-approved for spinal fusion for decades, its disadvantages of promoting osteoclast-based bone resorption and suboptimal carrier (absorbable collagen sponge) leading to premature release of the protein limit its clinical applications. Our recent study showed an excellent effect on
Regeneration of bone defects in elderly patients is limited due to the decreased function of bone forming cells and compromised tissue physiology. Previous studies suggested that the regenerative activity of stem cells from aged tissues can be enhanced by exposure to young systemic and tissue microenvironments. The aim of our project was to investigate whether extracellular matrix (ECM) engineered from human induced pluripotent stem cells (hiPSCs) can enhance the
Aims. Platelet concentrates, like platelet-rich plasma (PRP) and platelet lysate (PL), are widely used in regenerative medicine, especially in
Aims.
Mesoporous bioactive glasses (MBGs) have been widely studied as
Growing evidence has suggested that paracrine mechanisms of Mesenchymal stem cell (MSC) may be involved in the underlying mechanism of MSC after transplantation, and extracellular vesicles (EVs) are an important component of this paracrine role. The aim of this study was to investigate the in vitro osteogenic effects of EVs derived from undifferentiated mesenchymal stem cells and from chemically induced to differentiate into osteogenic cells for 7 days. Further, the osteoinductive potential of EVs for
Functionalization of biomimetic nanomaterials allows to reproduce the composition of native bone, permitting better regeneration, while nanoscale surface morphologies provide cues for cell adhesion, proliferation and differentiation. Functionalization of 3D printed and bioprinted constructs, by plasma-assisted deposition of calcium phosphates-based (CaP) nanostructured coatings and by nanoparticles, respectively, will be presented. Stoichiometric and ion doped CaP- based nanocoatings, including green materials (mussel seashells and cuttlefish bone), will be introduced to guide tissue regeneration. We will show interactions between biomimetic surfaces and MSCs to address
Due to the presence of megakaryocytes, platelets and clotting factors, bone marrow aspirate (BMA) tends to coagulate. For the first time, starting from our previous studies on mesenchymal vertebral stem cells, it has been hypothesized that coagulated BMA represents a safe and effective autologous biological scaffold for
Critical size bone defects are frequently caused by accidental trauma, oncologic surgery, and infection. Distraction osteogenesis (DO) is a useful technique to promote the repair of critical size bone defects. However, DO is usually a lengthy treatment, therefore accompanied with increased risks of complications such as infections and delayed union. Herein, we developed an innovative intramedullary biodegradable magnesium (Mg) nail to accelerate
Objectives. Mesenchymal stem cells (MSCs) are of growing interest in terms of
The Masquelet technique is a variable method for treating critical-sized bone defects, but there is a need to develop a technique for promoting
During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance
Recent studies suggested that both the soluble protein of the mesenchymal stromal cell (MSC) secretome, as well as the secreted extracellular vesicles (EVs) promote
The regenerative capacity of hyaline cartilage is greatly limited. To prevent the onset of osteoarthritis, cartilage defects have to be properly treated. Cartilage, tissue engineered by mean of bioactive glass (BG) scaffolds presents a promising approach. Until now, conventional BGs have been used mostly for
Bone defects and fractures, caused by injury, trauma or tumour resection require hospital treatment and temporary loss of mobility, representing an important burden for societies and health systems worldwide. Autografts are the gold standard for promoting new bone formation, but these may provide insufficient material and lead to donor site morbidity and pain. We previously showed that Fibrinogen (Fg) scaffolds promote
Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of
Aim. Aim of this monocentric, prospective study was to evaluate the safety, efficacy, clinical and radiographical results at 24-month follow-up (N = 6 patients) undergoing hip revision surgery with severe acetabular bone defects (Paprosky 2C-3A-3B) using a combination of a novel phase-pure betatricalciumphosphate - collagen 3D matrix with allograft bone chips. Method. Prospective follow-up of 6 consecutive patients, who underwent revision surgery of the acetabular component in presence of massive bone defects between April 2018 and July 2019. Indications for revision included mechanical loosening in 4 cases and history of hip infection in 2 cases. Acetabular deficiencies were evaluated radiographically and CT and classified according to the Paprosky classification. Initial diagnosis of the patients included osteoarthritis (N = 4), a traumatic fracture and a congenital hip dislocation. 5 patients underwent first revision surgery, 1 patient underwent a second revision surgery. Results. All patients were followed-up radiographically with a mean of 25,8 months. No complications were observed direct postoperatively. HHS improved significantly from 23.9 preoperatively to 81.5 at the last follow-up. 5 patients achieved a defined good result, and one patient achieved a fair result. No periprosthetic joint infection, no dislocations, no deep vein thrombosis, no vessel damage, and no complaint about limbs length discrepancy could be observed. Postoperative dysmetria was found to be + 0.2cm (0cm/+1.0cm) compared to the preoperative dysmetria of − 2.4 cm (+0.3cm/−5.7cm). Conclusions. Although used in severe acetabular bone defects, the novel phase-pure betatricalciumphosphate - collagen 3D matrixshowed complete resorption and replacement by newly formed bone, leading to a full implant integration at 24 months follow-up and thus represents a promising method with excellent
Various approaches have been implemented to enhance
Bone is a dynamic tissue that undergoes continuous mechanical forces. Mechanical stimuli applied on scaffolds resembling a part of the human bone tissue affects the osteogenesis [1]. Poly(3,4-ethylenedioxythiophene) (PEDOT) is a piezoelectric material that responds to mechanical stimulation producing an electrical signal, which in turn promotes the osteogenic differentiation of bone-forming cells by opening voltage-gated calcium channels [2]. In this study we examined the biological behavior of pre-osteoblastic cells seeded onto lyophilized piezoelectric PEDOT-containing scaffolds applying uniaxial compression. Two different concentrations of PEDOT (0.10 and 0.15% w/v) were combined with a 5% w/v poly(vinyl alcohol) (PVA) and 5% w/v gelatin, casted into wells, freeze dried and crosslinked with 2% v/v (3-glycidyloxypropyl)trimethoxysilane and 0.025% w/v glutaraldehyde. The scaffolds were physicochemically characterized by FTIR, measurement of the elastic modulus, swelling ratio and degradation rate. The cell-loaded scaffolds were subjected to uniaxial compression with a frequency of 1 Hz and a strain of 10% for 1 h every second day for 21 days. The loading parameters were selected to resemble the in vivo loading situation [3]. Cell viability and morphology on the PEDOT/PVA/gelatin scaffolds was determined. The alkaline phosphatase (ALP) activity, the collagen and calcium production were determined. The elastic modulus of PEDOT/PVA/gelatin scaffolds ranged between 1 and 5 MPa. The degradation rate indicates a mass loss of 15% after 21 days. The cell viability assessment displays excellent biocompatibility, while SEM images display well-spread cells. The ALP activity at days 3, 7 and 18 as well as the calcium production are higher in the dynamic culture compared to the static one. Moreover, energy dispersive spectroscopy analysis revealed the presence of calcium phosphate in the extracellular matrix after 14 days. The results demonstrate that PEDOT/PVA/gelatin scaffolds promote the adhesion, proliferation, and osteogenic differentiation of pre-osteoblastic cells under mechanical stimulation, thus favoring
In this work, we combined tissue engineering and gene therapy technologies to develop a therapeutic platform for
Bone morphogenetic proteins (BMPs) have been widely investigated for treating non-healing fractures. They participate in bone reconstruction by inducing osteoblast differentiation, and osteoid matrix production. 1. The human recombinant protein of BMP-7 was among the first growth factors approved for clinical use. Despite achieving comparable results to autologous bone grafting, severe side effects have been associated with its use. 2. Furthermore, BMP-7 was removed from the market. 3. These complications are related to the high doses used (1.5-40 miligrams per surgery). 2. compared to the physiological concentration of BMP in fracture healing (in the nanogram to picogram per milliliter range). 4. In this study, we use transcript therapy to deliver chemically modified mRNA (cmRNA) encoding BMP-7. Compared to direct use of proteins, transcript therapy allows the sustained synthesis of proteins with native conformation and true post-translational modifications using doses comparable to the physiological ones. 5. Moreover, cmRNA technology overcomes the safety and affordability limitations of standard gene therapy i.e. pDNA. 6. BMP-7 cmRNA was delivered using Lipofectamine™ MessengerMAX™ to human mesenchymal stromal cells (hMSCs). We assessed protein expression and osteogenic capacity of hMSCs in monolayer culture and in a house-made, collagen hydroxyapatite scaffold. Using fluorescently-labelled cmRNA we observed an even distribution after loading complexes into the scaffold and a complete release after 3 days. For both monolayer and 3D culture, BMP-7 production peaked at 24 hours post-transfection, however cells transfected in scaffolds showed a sustained expression. BMP-7 transfected hMSCs yielded significantly higher ALP activity and Alizarin red staining at later timepoints compared to the untransfected group. Interestingly, BMP-7 cmRNA treatment triggered expression of osteogenic genes like OSX, RUNX-2 and OPN, which was also reflected in immunostainings. This work highlights the relevance of cmRNA technology that may overcome the shortcomings of protein delivery while circumventing issues of traditional pDNA-based gene therapy for
The need for an artificial scaffold in very large bone defects is clear, not only to limit the risk of graft harvesting, but also to improve clinical success. The use of custom osteoconductive scaffolds made from biodegradable polyester and ceramics can be a valuable patient friendly option, especially in case of a concomitant infection. Multiple types of scaffolds for the Masquelet procedure (MP) are available, however these frequently demonstrate central graft involution when defects exceed a certain size and the complication rates remains high. This paper describes three infected tibial defect nonunions with a segmental defect over ten centimeters long treated with a customized 3D printed polycaprolactone-tricalcium phosphate (PCL-TCP) cage in combination with biological adjuncts. Three male patients, between the age of 37 and 47, were treated for an infected tibial defect nonunion after sustaining Gustilo grade 3 open fractures. All had a segmental midshaft bone defect of more than ten centimeters (range 11–15cm). First stage MPs consisted of extensive debridement, external fixation and placement of anterior lateral thigh flaps (ALT). Positive cultures were obtained from all patients during this first stage, that were treated with specific systemic antibiotics during 12 weeks. The second stage MP was carried out at least two months after the first stage. CT scans were obtained after the first stage to manufacture defect-specific cages. In the final procedure a custom 3D printed PCL-TCP cage (Osteopore, Singapore) was placed in the defect in combination with biological adjuncts (BMAC, RIA derived autograft, iFactor and BioActive Glass). Bridging of the defect, assessed at six months by CT, was achieved in all cases. SPECT-scans 6 months post-operatively demonstrated active
The growing number of non-union fractures in an aging population has increased the clinical demand for tissue-engineered bone. Electrical stimulation (ES) has been described as a promising strategy for
The human amniotic membrane (hAM) may be helpful as a support for
Decreasing the chance of local relapse or infection after surgical excision of bone metastases is a main goals in orthopedic oncology. Indeed, bone metastases have high incidence rate (up to 75%) and important cross-relations with infection and
Introduction. “Bioexpandable” prostheses after resection of malignant bone tumors in children to lengthen the bone using the method of callus distraction may offer new perspectives and better long-term results. Materials and Methods. The bioexpandable prosthesis is equipped with an encapsulated electromotor which enables the device to perform distraction in an osteotomy gap with about 1mm/day. The new bone is improving the ratio from bone to prosthesis and therewith the potential stability of the final stem. The device is indicated, when limb length discrepancy is getting more than 3 cm or at maturity and can be used in a minimal invasive way for femur lengthening. Results. 11 patients were treated with the bioexpandable prosthesis. The mean age of the patients was 13,5 years and the mean amount of lengthening was 74mm. In 2 cases lengthening was performed in 2 steps and in 1 case in 3 steps. All lengthening procedures could be finished without complications. There was no infection and no technical problem. The
Introduction. Fibrous dysplasia is a pathological condition, where normal medullary bone is replaced by fibrous tissue and small, woven specules of bone. Fibrous dysplasia can occur in epiphysis, metaphysis or diaphysis. Occationally, biopsy is necessary to establish the diagnosis. We present a review of operative treatment using the Ilizarov technique. The management of tibial fibrous dysplasia in children are curettage or subperiosteal resection to extra periosteal wide resection followed by bone transport. Materials and Methods. A total of 18 patients were treated between 2010 – 2020; 12 patients came with pain and 6 with pain and deformity. All patients were treated by Ilizarov technique. Age ranges from 4–14 years. 12 patients by enbloc excision and bone transportation and 6 patients were treated by osteotomy at the true apex of the deformity by introducing the k/wires in the medullary cavity with stable fixation by Ilizarov device. The longest duration for bone transport was 16 weeks (14–20 weeks) for application, after deformity correction was 20 weeks. We have never used any kind of bone grafts. Results. All the 18 patients were treated successfully by Ilizarov compression distraction device. The patients with localized tibial pathology with deformity had the shortest period on the Ilizarov apparatus, 14 weeks. Conclusions. Preservation and
Promising work on bioactive glasses (BAGs) in
Bioactive functional scaffolds are essential for support of cell-based strategies to improve
Intra-articular infusions of adipose tissue-derived stem cells (ASCs) are a promising tool for
Treatment of large bone defects represents a great challenge for orthopedic surgeons. The main causes are congenital abnormalities, traumas, osteomyelitis and bone resection due to cancer. Each surgical method for bone reconstruction leads its own burden of complications. The gold standard is considered the autologous bone graft, either of cancellous or cortical origin, but due to graft resorption and a limitation for large defect, allograft techniques have been identified. In the bone defect, these include the placement of cadaver bone or cement spacer to create the ‘Biological Chamber’ to restore
The human amniotic membrane (hAM), derived from the placenta, possesses a low (nay inexistant) immunogenicity and exerts an anti-inflammatory, anti-fibrotic, antimicrobial, antiviral and analgesic effect. It is a source of stem cells and growth factors promoting tissue regeneration. hAM acts as an anatomical barrier with adequate mechanical properties (permeability, stability, elasticity, flexibility, resorbability) preventing the proliferation of fibrous tissue and promoting early neovascularization of the surgical site. Cryopreservation and lyophilization, with sometimes additional decellularization process, are the main preservation methods for hAM storage. We examined the use of hAM in orthopaedic and maxillofacial bone surgery, specially to shorten the induced membrane technique (Gindraux, 2017). We investigated the cell survival in cryopreserved hAM (Laurent, 2014) and the capacity of intact hAM of in vitro osteodifferentiation (Gualdi, 2019). We explored its in vivo osteogenic potential in an ectopic model (Laurent, 2017) and, with Inserm U1026 BioTis, in a calvarial defect (Fenelon, 2018). Still piloted by U1026, decellularization and/or lyophilization process were developed (Fenelon, 2019) and, processed hAM capacities was assessed for guided
Introduction and Objective. The early pro-inflammatory hematoma phase of bone healing is characterized by platelet activation followed by growth factor release. Bone marrow mesenchymal stromal cells (MSC) play a critical role in
Aim.
Objectives. Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage–mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male versus female cocultures. Methods. A primary murine macrophage-MSC coculture system was used to demonstrate the optimal transition time from M1 to M2 (polarized from M1 with interleukin (IL)-4) macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase (ALP) activity, and osteocalcin protein secretion. Results. We found that 96 hours of M1 phenotype in male cocultures allowed for maximum matrix mineralization versus 72 hours in female cocultures. ALP activity and osteocalcin secretion were also enhanced with the addition of IL-4 later in male versus female groups. The sex of the cells had a statistically significant effect on the optimal IL-4 addition time to maximize osteogenesis. Conclusion. These results suggest that: 1) a 72- to 96-hour proinflammatory environment is critical for optimal matrix mineralization; and 2) there are immunological differences in this coculture environment due to sex. Optimizing immunomodulation during fracture healing may enhance and expedite the
Introduction and Objective. Mesenchymal stem cells (MSC) are attractive candidates for
Introduction and Objective. Guided Bone Regeneration (GBR) uses biodegradable collagen membranes of animal origin tissues (dermis and pericardium). Their barrier effect prevents soft tissues to interfere with the regeneration of alveolar bone. However, their xenogeneic origin involves heavy chemical treatments which impact their bioactivity. Wharton's Jelly (WJ) from the umbilical cord is a recoverable surgery waste. WJ is mostly made from collagen fibers, proteoglycans, hyaluronic acid, and growth factors. WJ with immunologically privileged status and bioactive properties lends credence to its use as an allograft. Nevertheless, low mechanical properties limit its use in
Aim. Osteomyelitis is a difficult-to-treat disease with high chronification rates. The surgical amputation of the afflicted limb sometimes remains as the patients’ last resort. Several studies suggest an increase in mitochondrial fission as a possible contributor to the accumulation of intracellular reactive oxygen species and thereby to cell death of infectious bone cells. The aim of this study is to analyze the ultrastructural impact of bacterial infection and its accompanying microenvironmental tissue hypoxia on osteocytic and osteoblastic mitochondria. Method. 19 Human bone tissue samples from patients with osteomyelitis were visualized via light microscopy and transmission electron microscopy. Osteoblasts, osteocytes and their respective mitochondria were histomorphometrically analyzed. The results were compared to the control group of 5 non-infectious human bone tissue samples. Results. The results depicted swollen hydropic mitochondria including depleted cristae and a decrease in matrix density in the infectious samples as a common finding in both cell types. Furthermore, perinuclear clustering of mitochondria could also be observed regularly. Additionally, increases in relative mitochondrial area and number could be found as a sign for increased mitochondrial fission. Conclusions. The results show that mitochondrial morphology is altered during osteomyelitis in a comparable way to mitochondria from hypoxic tissues. This suggests that manipulation of mitochondrial dynamics in a way of inhibiting mitochondrial fission may improve bone cell survival and exploit
Introduction and Objective. The choice of appropriate characteristics is crucial to favor a firm bonding between orthopedic implants and the host bone and to permit
Ceramics such as hydroxyapatite are routinely used in fracture repair. However, their effects could be significantly improved as its bioavailability is incredibly poor (issues including low solubility, anionic charge, tendency to agglomerate). Nanoscale hydroxyapatite are gaining much interest, demonstrating increased effectiveness when compared to their micro-sized counterpart. In this study, we have developed a bioactive cargo–polymer-based system that allowed for the sustained, localised non-viral delivery of hydroxyapatite nanoparticles using an amphipathic peptide as a capping agent. The nanoparticles were delivered from a polycaprolactone nanofibre reinforced novel Alg-co-PNIPAAm thermoresponsive hydrogel. The bioactive cargo–polymer-based system was characterised in terms of its physiochemical properties, in vitro properties and in vivo performance using a subcutaneous mouse model. From this study, we have demonstrated that osteogenesis and
Introduction and Objective. In multiple trauma patients, as well as in the healing of isolated fractures (Fx) with heavy bleeding (trauma haemorrhage, TH), complications occur very often. This is particularly evident in elderly patients over 65 years of age. Since these accompanying circumstances strongly influence the clinical course of treatment, the influence of age on
Regeneration of bone defects in elderly patients is limited due to the decreased function of bone forming cells and compromised tissue physiology. Previous studies suggested that the regenerative activity of stem cells from aged tissues can be enhanced by exposure to young systemic and tissue microenvironments. The aim of our project was to investigate whether extracellular matrix (ECM) engineered from human induced pluripotent stem cells (hiPSCs) can enhance the
All types of regenerative materials, including metal implants, porous scaffolds and cell-laden hydrogels, interact with the living tissue and cells. Such interaction is key to the settlement and regenerative outcomes of the biomaterials. Notably, the immune reactions from the host body crucially mediate the tissue-biomaterials interactions. Macrophages (as well as monocytes and neutrophils), traditionally best known as defenders, accumulate at the tissue-biomaterials interface and secrete abundant cytokines to create a microenvironment that benefits or inhibits regeneration. Because the phenotype of these cells is highly plastic in response to varying stimuli, it may be feasible to manipulate their activity at the interface and harness their power to mediate
Sustained release of BMP-2 is reported to be able to reduce the required dose of BMP-2 for bone induction. Nanohydroxyapatite (nHAp) has an osteoinduction capability which is lack in conventional hydroxyapatite. In this study, we combined PLA-PEG with nHAp and investigated the
Nitrogen-containing bisphosphonates such as Zoledronic Acid (ZA) are used clinically for the treatment of skeletal diseases related with increased bone resorption. The gold standard is to administrate the drug through a systemic pathway, however this is often associated with high dosages, risk of side-effects, reduced site-specific drug delivery and hence, limited drug-effectiveness. A controlled local drug delivery, via a biomimetic bone graft, could be beneficial by direct and time-regulated application of significantly lower drug dosage at the site of interest. Thus, higher efficacy and reduced side-effects could be expected. In this experimental in vivo study, we examined the effect of ZA when used together with a Calcium Sulphate/Hydroxyapatite biomaterial in a femoral condyle bone defect in rats and compared local to systemic administration. The following groups were used: group1: empty defect (no biomaterial & no treatment), group2: biomaterial alone, group3: biomaterial + systemic ZA (0.1mg ZA/kg – single subcutaneous injection), group4–6: biomaterial conjugated with ZA at different concentrations, (0.07 to 0.70 mg ZA/mL of paste, corresponding to 0.0024 to 0.024 mg ZA/kg). The animals were sacrificed at 6 weeks and toxicological examination was performed.
Favoring osseointegration and avoiding bacterial contamination are the key challenges in the design of implantable devices for orthopedic applications. To meet these goals, a promising route is to tune the biointerface of the devices, that can regulate interactions with the host cells and bacteria, by using nanostructured antibacterial and bioactive coatings. Indeed, the selection of adequate metal-based coatings permits to discourage infection while avoiding the development of bacterial resistance and nanostructuring permits to tune the release of the antimicrobial compounds, allowing high efficacy and decreasing possible cytotoxic effects. In addition, metal-doped calcium phosphates-based nanostructured coatings permit to tune both composition and morphology of the biointerfaces, allowing to regulate host cells and bacteria response. To tune the biointerfaces of implantable devices, nanostructured coatings can be used, but their use is challenging when the substrate is heat-sensitive and/or porous. Here, we propose the use of Ionized Jet Deposition (IJD) to deposit metallic and ion-doped calcium phosphates materials onto different polymeric substrates, without heating and damaging the substrate morphology. 3D printed scaffolds in polylactic acid (PLA) and polyurethane (PU), and electrospun matrices in polycaprolactone (PCL) and PLA were used as substrates. Biogenic apatite (HA), ion doped (zinc, copper and iron) tricalcium phosphate (TCP) and silver (Ag) coatings were obtained on porous and custom-made polymeric substrates. Chemical analyses confirmed that coatings composition matches that of the target materials, both in terms of main phase (HA or TCP) and ion doping (presence of Cu, Zn or Fe ion). Deposition parameters, and especially its duration time, influence the coating features (morphology and thickness) and substrate damage. Indeed, SEM/EDS observations show the presence of nanostructured agglomerates on substrates surface. The dimensions of the aggregates and the thickness of the coating films increase increasing the deposition time, without affecting the substrate morphology (no porosity alteration or fibers damaging). The possible substrate damage is influenced by target and substrate material, but it can be avoided modulating deposition time. Once the parameters are optimized, the models show suitable in vitro biological efficacy for applications in
Healthy bone metabolism is a tightly coupled dynamic process that relies on a balance between bone resorption (catabolism) by osteoclasts and bone formation (anabolism) by osteoblasts. Traditionally, tissue-engineering approaches for non-union fracture repair employ local anabolic therapeutic delivery strategies that target mesenchymal stem cells (MSCs) and osteoblasts to induce bone formation, however, the challenge of healing non-union defects depends on the cause of defect e.g. trauma or disease, and targeting bone formation alone is often not sufficient. Our research focuses on utilising both anabolic therapeutics, including recombinant human bone morphogenic protein (rhBMP) −2 and parathyroid hormone (PTH). (1–34). , and anti-catabolic bisphosphonates (BPs) to target bone metabolism. A major challenge with harnessing a combined dosing regimen is controlling the release of the individual therapeutics to target cells. We have developed a number of polymer-ceramic based biomaterial delivery systems, including injectable and implantable scaffolds, for the controlled release of rhBMP-2 and the BP zoledronic acid (ZA) and demonstrated their efficacy in vivo. A dual therapeutic load provided a synergistic enhancement of
In the treatment of bone non-unions an alternative to bone autografts is the use of bone morphogenetic proteins (BMP-2, BMP-7) with powerful osteoinductive and osteogenic properties. In clinical settings, BMPs are applied using absorbable collagen sponges. Supraphysiological doses are needed and major side effects may occur as induce ectopic bone formation, chronic inflammation and excessive bone resorption. In order to increase the efficiency of the delivered for BMPs we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic, ANI) or trabecular bone (random distributed porosity, isotropic, ISO). We hypothesize that anisotropic structure would enhance osteoconductive properties of the scaffolds increasing rhBMP-2 regenerative properties. In vitro, both scaffolds presented similar mechanical properties, rhBMP-2 retention and delivery capacity. For in vivo testing, a rat femoral critical size defect model was created. Four groups were assessed depending on the implant applied to the bone defect: ISO, unloaded isotropic sponge; ISO-BMP, isotropic sponge loaded with 5 μg of hrBMP-2; ANI, unloaded anisotropic sponge; and ANI-BMP, anisotropic sponge loaded with 5 μg of hrBMP-2. Regeneration was allowed for 10 weeks. X-ray, μCT, biomechanical testing and histology were used to evaluate repair. Independently of their structure, sponges loaded with rhBMP-2 demonstrate increased bone volume, and biomechanical properties than their controls (p<0.01 and p<0.05 respectively). Globally, ANI-BMP group demonstrated better
Summary. MSCs could promote
Summary Statement. A coupled finite element - analytical model is presented to predict and to elucidate a clinical healing scenario where
Fracture non-union can be as high as 20% in certain clinical scenarios and has a high associated socioeconomic burden. Boron has been shown to regulate the Wnt/β-catenin pathway in other bodily processes. However, this pathway is also critical for bone healing. Here we aim to demonstrate that the local delivery of boric acid can accelerate bone healing, as well as to elucidate how boric acid, via the regulationtheWnt/β-catenin pathway, impacts theosteogenic response of bone-derived osteoclasts and osteoblasts during each phase of bone repair. Bilateral femoral cortical defects were created in 32 skeletally mature C57 mice. On the experimental side, boric acid (8mg/kg concentration) was injected locally at the defect site whereas on the control side, saline was used. Mice were euthanized at 7, 14, and 28 days. MicroCT was used to quantify
Objectives. Distraction osteogenesis (DO) mobilises
Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in
Mice are increasingly used for fracture healing research because of the possibility to use transgenic animals to conduct research on the molecular level. Mice from both sexes can be used, however, there is no consensus in the literature if fracture healing differs between female and male mice. Therefore, the aim of the present study was to analyze the similarities and differences in endochondral fracture healing between female and male C57BL/6J mice, since this mouse strain is mainly used in bone research. For that purpose, 12-weeks-old female and male mice received a standardized femur midshaft osteotomy stabilized by an external fixator. Mice were euthanized 10 and 21 days after fracture and
The regenerative potential of bone is enormous, and it is possible to lengthen limbs by bone distraction. However, there remains a major risk of fracture after lengthening the bone. Previous studies have described how the pixel value ratio may be used for determining the time for frame removal. The aim of this study was to investigate the intrarater and the interrater reliability of pixel value scores from radiographs in tibial lengthening prior to frame removal. Moreover, the study aimed to determine the overall number of X- rays obtained during circular frame treatment. Retrospective study. Patients treated with tibial lengthening by a circular frame at Aalborg University Hospital from January 1st 2000 to December 31st 2017 and a minimum of 12 months after frame removal were included. The bone was divided in proximal-, regenerate- and distal bone zone. These 3 zones were in AP x-ray divided in an anterior and posterior zone and in sagittal X-ray medial and lateral zone producing 6 zones in which the pixel value was measured. Pixel value ratio was calculated as: (Proximal pixel value+Distal pixel value)/2/Regenerate pixel value. Interrater correlations were calculated from measurements obtained by an orthopaedic registrar and an orthopaedic specialist. Intrarater correlation was calculated from repeated measurements obtained by an orthopaedic specialist. Mean duration of circular frame treatment was: 6 (+-3) months. Median number of x-ray controls during frame treatment were: 9 (+-4). Out of 90 tibial lengthening it was only possible to measure pixel value in all six areas of interest on 20 lengthening prior to frame removal. Major reasons for inability to obtain measurements were metal hardware crossing the areas of bone interest on x-rays. The mean (95 % confidence intervals) pixel ratios values were: 1) lateral: 0.96 (0.93–1.00); 2) medial: 0.95 (0.92–0.99); 3) anterior: 0.94 (0.90–0.97); 4) posterior: 0.96 (0.93–0.99). The mean (95 % confidence intervals) inter ratter ICC estimates were: 1) lateral: 0.8 (0.5–0.9); 2) medial: 0.8 (0.4–0.9); 3) anterior: 0.4 (−0.5–0.8); 4) posterior: 0.6 (0.1–0.9). The mean (95 % confidence intervals) intra ratter ICC estimates were: 1) lateral: 1.0 (0.9–1.0); 2) medial: 1.0 (1.0–1.0); 3) anterior: 0.9 (0.9–1.0); 4) posterior: 1.0 (1.0–1.0). Out of the 20 lengthening examined one fracture occurred in the
The transtrochanteric anterior rotational osteotomy (TRO) was developed by Sugioka as a joint-preserving procedure which prevents further deformity by transposing the necrotic area from a site of primary weight-bearing to a secondary area. We performed this procedure for children and young adults with various hip disorders. Between 1994 and 2015 we performed TROs on 12 joints in 12 patients with SCFE (4), pigmented villonodular synovitis (2), septic arthritis (1), FAI (1), hip dysplasia (1), femoral neck fracture (2) and postoperative RAO (1). The mean age at the time of surgery was 21 years (10–43) and the mean follow-up period was 8 years (1–22). The rotational directions of the femoral head were anterior (5) and posterior (7). Clinical assessment was undertaken using the system of Merle d'Aubigné and Postel, grading pain, mobility and walking ability with scores from 0 to 6. Radiographically
Summary: Investigation of the specific roles of circulating mesenchymal progenitor cells, YKL-40 and IL-6 during regeneration of planned or traumatic bone traumas. Introduction: YKL-40 is a growth factor with possible involvement in regeneration of mesenchymal tissue. IL-6 is a pro-inflammatory marker. Mesenchymal progenitor cells (MPC), is a subpopulation of mononuclear cells (MNC), involved in
First works focuses on the characterization (physical and biological) of this biomaterial. Current work had studied osteoinductive and osteoconductive capacity of these hydrogels. In vivoresults highlight a significant bone reconstruction two months after implantations on bone lesions in mice. Bone is a dynamic and vascularized tissue that has the ability of naturally healing upon damage. Nevertheless, in the case of critical size defects this potential is impaired. Present approaches mainly consider autografts and allografts, which presents several limitations. Bone Tissue Engineering (BTE) is based on the use of 3D matrices to guide both cellular growth, differentiation to promote
Confirming clinical evidence, we recently demonstrated in a rodent model that a severe trauma which induces an acute systemic inflammation considerably impairs fracture healing. Interleukin-6 (IL-6) is a key cytokine in posttraumatic inflammation as its serum level correlates with injury severity and mortality. IL-6 signals are transmitted by the transmembrane glycoprotein 130 (gp130) via two distinct mechanisms: firstly, through classic signalling via the membrane-anchored IL-6 receptor and secondly, through trans-signalling using a soluble IL-6 receptor. Whereas IL-6 trans-signalling is considered a danger signal driving inflammation, classic signalling may mediate anti-inflammatory, pro-regenerative processes. The role of the two distinct pathways in bone healing has not yet been elucidated. Here, we studied the function of IL-6 in the pathophysiology of compromised bone healing induced by severe trauma. Male C57BL/6J mice received an osteotomy of the right femur stabilized with an external fixator. Systemic inflammation was induced by additional blunt chest trauma (TxT) applied immediately after the osteotomy. Mice were injected with either fusion protein sgp130Fc, which selectively inhibits IL-6 trans-signalling, or a neutralizing anti-IL-6 antibody (IL-6 Ab), blocking both signalling pathways. Control mice received vehicle solution. Animals were euthanised 21 days after surgery. Fracture healing was analysed by biomechanical testing, μCT, and histomorphometry (n= 6–9; p=0.05; ANOVA/Fisher LSD post hoc). Thoracic trauma significantly impaired fracture healing [bending stiffness (EI) −57%, p<0.00]. Treatment with sgp130Fc significantly attenuated
Objectives. To compare the therapeutic potential of tissue-engineered constructs (TECs) combining mesenchymal stem cells (MSCs) and coral granules from either Acropora or Porites to repair large bone defects. Materials and Methods. Bone marrow-derived, autologous MSCs were seeded on Acropora or Porites coral granules in a perfusion bioreactor. Acropora-TECs (n = 7), Porites-TECs (n = 6) and bone autografts (n = 2) were then implanted into 25 mm long metatarsal diaphyseal defects in sheep. Bimonthly radiographic follow-up was completed until killing four months post-operatively. Explants were subsequently processed for microCT and histology to assess bone formation and coral bioresorption. Statistical analyses comprised Mann-Whitney, t-test and Kruskal–Wallis tests. Data were expressed as mean and standard deviation. Results. A two-fold increaseof newly formed bone volume was observed for Acropora-TECs when compared with Porites-TECs (14 . sd. 1089 mm. 3. versus 782 . sd. 507 mm. 3. ; p = 0.09). Bone union was consistent with autograft (1960 . sd. 518 mm. 3. ). The kinetics of bioresorption and bioresorption rates at four months were different for Acropora-TECs and Porites-TECs (81% . sd. 5% versus 94% . sd. 6%; p = 0.04). In comparing the defects that healed with those that did not, we observed that, when major bioresorption of coral at two months occurs and a scaffold material bioresorption rate superior to 90% at four months is achieved, bone nonunion consistently occurred using coral-based TECs. Discussion.
Background. Calcium orthophosphates, such as hydroxyapatite (Ca5(PO4)3OH) (HA), have long been employed as bone graft materials. Recent work has suggested that calcium pyrophosphate (Ca2P2O7) (CaPy) may strongly stimulate bone deposition. In this study we compare calcium orthophosphate and pyrophosphate precipitates as suitable
Purpose: Bone grafting of subchondral voids during ORIF of tibial plateau fractures is commonly performed. The efficacy of various graft materials to resist post-operative articular displacement and stimulate
Osteoinductive bone substitutes are in their developmental infancy and a paucity of effective grafts options persists despite clinical demand. Bone mineral substitutes such as hydroxyapatite cause minimal biological activity when compared to osteoinductive systems present biological growth factors in order to drive
A novel injectable hydrogel based on DNA and silicate nanodisks was fabricated and optimized to obtain a suitable drug delivery platform for biomedical applications. Precisely, the hydrogel was designed by combining two different type of networks: a first network (type A) made of interconnections between neighboring DNA strands and a second one (type B) consisting of electrostatic interactions between the silicate nanodisks and the DNA backbone. The silicate nanodisks were introduced to increase the viscosity of the DNA physical hydrogel and improve their shear-thinning properties. Additionally, the silicate nanodisks were selected to modulate the release capability of the designed network. DNA 4% solutions were heated at 90°C for 45 seconds and cooled down at 37°C degree for two hours. In the second step, the silicate nanodisks suspension in water at different concentrations (0.1 up to 0.5%) were then mixed with the pre-gel DNA hydrogels to obtain the nanocomposite hydrogels. Rheological studies were carried out to investigate the shear thinning properties of the hydrogels. Additionally, the hydrogels were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron microscopy. The hydrogels were loaded with the osteoinductive drug dexamethasone and its release was tested in vitro in phosphate buffer pH 7.4. The drug activity upon release was tested evaluating the osteogenic differentiation of human adipose derived stem cells (hASCs) in vitro through analysis of main osteogenic markers and quantification of alkaline phosphatase activity and calcium deposition. Finally, the hydrogels were tested in vivo and injected into cranial defects in rats to assess their biocompatibility and
Previously, we reported impaired biomechanical bone properties and inferior bone matrix quality in tachykinin1 (Tac1)-deficient mice lacking the sensory neuropeptide substance P (SP). Additionally, fracture callus development is affected by the absence of SP indicating a critical effect of sensory nerve fibers on bone health and regeneration. For α-calcitonin gene-related peptide (α-CGRP)-deficient mice, a profound distortion of bone microarchitecture has also been described. We hypothesize that SP and α-CGRP modulate inflammatory as well as pain-related processes and positively affect
Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects. We performed a retrospective review at a single institution of patients undergoing revision THA by a single surgeon. We identified 49 consecutive patients with large acetabular defects where the biphasic BGS was applied, with no other products added to the BGS. After placement of metallic acetabular implants, the BGS was injected into the remaining bone defects surrounding the new implants. Patients were followed and monitored for functional outcome scores, implant fixation, radiological graft site remodelling, and revision failures.Aims
Methods
Purpose: The purpose of this study was to evaluate centromedullary pinning for bone lengthening. We studied an animal model to discover the details of
Summary Statement. Low-intensity pulsed ultrasound (LIPUS) enhanced osteogenic differentiation of osteoprogenitor cells derived from mouse induced pluripotent cells (iPSCs) without embryoid body formation. Our findings provide insights on the development of LIPUS as an effective technology for
Bone grafts are crucial for the treatment of bone defects caused by tumor excision. The gold standard is autograft but their availability is limited. Allografts are an alternative, but there is a risk of rejection by the immune system. The tissue engineering field is trying to develop vascularized bone grafts, using innovative biomaterials for surgery applications. While the gold standard in bone graft in dentistry is the use of decellularized bovine bone particles (Bio-Oss®), our work has produced a polysaccharide-based composite matrix (composed of PUllulan, DextraNand particles of HydroxyApatite (PUDNHA), as a new scaffold for promoting bone formation and vascularization of the tissue. In the context of bone tissue regeneration, the function of osteoblast and endothelial cells has been extensively studied, while the impact of osteocytes has been regarded as secondary. Nonetheless, the osteocytes represent 90–95% of bone cells and are responsible for orchestration of bone remodeling. Here, we propose an original method to analyze the interaction between bone and biomaterials, after in vivo implantation of the matrix PUDNHA in an experimental sheep model. Our objectives are to analyze the network established by osteocytes in the newly formed tissue induced by the matrix, as well as their interactions with the blood vessels. Sheep have been implanted with the Bio-Oss® or the PUDNHA using the sinus lift technique. After 3 (3M) and 6 months (6M), the animals were euthanazied and the explants were fixed, analyzed by X-ray, embedded in Methylmetacrylate/Buthylmetacrylate and analyzed histologically by Trichrome staining. Thereafter, the samples (n=3/group) were polished using different sand papers. A final polish was realized using a 1µm Diamond polishing compound. The blocks were incubated 10 or 30s with 37% phosphoric acid to remove the mineral on the surface, then dipped in 2.6% sodium hypochlorite to remove the collagen. The samples were air dried overnight, metallized with Gold palladium the following day, before being imaged with a SEM. As expected, PUDNHA activates
The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase.Aims
Methods
Aims: The study we present compares quantitatively the
