Purpose. Bone morphogenic protein (BMP-2) is used in spinal arthrodesis to induce bone growth. Studies have demonstrated that it achieves similar fusion rates compared to iliac crest bone graft when used in instrumented fusions. Our study aims at evaluating the requirement for instrumentation in one and two-level spinal arthrodeses when
Impaired bone healing biology secondary to soft tissue deficits and chemotherapy contribute to non-union, fracture and infection following limb salvage surgery in Osteosarcoma patients. Approved bone healing augments such as recombinant human bone morphogenetic protein-2 (rhBMP-2) have great potential to mitigate these complications. rhBMP-2 use in sarcoma surgery is limited, however, due to concerns of pro-oncogenic signalling within the tumour resection bed. To the contrary, recent pre-clinical studies demonstrate that
Impaired bone healing biology secondary to soft tissue deficits and chemotherapy contribute to non-union, fracture and infection following limb salvage surgery in Osteosarcoma patients. Approved bone healing augments such as recombinant human bone morphogenetic protein-2 (rhBMP-2) have great potential to mitigate these complications. rhBMP-2 use in sarcoma surgery is limited, however, due to concerns of pro-oncogenic signalling within the tumour resection bed. To the contrary, recent pre-clinical studies demonstrate that
Titanium (Ti) is well known in orthopedic implant materials such as total hip replacement arthroplasty. Osseointegration of orthopedic implants is defined as the formation of a direct interface between the implant and the bone without intervening soft tissue. Unmodified Ti is not sufficient to complete adhesion between Ti surface and host bone with subsequent implant loosening over time and ultimately implant failure. An effective approach to enhance the biological activity of orthopedic implants and improve post-implantation healing is to modify the implant surface. The aim of this study was to investigate the effect of functionalized titanium (Ti) with alendronate (Aln) and bone morphogenic protein-2 (BMP-2) for enhancement of osteoblast activity in vitro. Aln and/or
Periosteum is important for bone homoeostasis
through the release of bone morphogenetic proteins (BMPs) and their
effect on osteoprogenitor cells. Smoking has an adverse effect on
fracture healing and bone regeneration. The aim of this study was
to evaluate the effect of smoking on the expression of the BMPs
of human periosteum. Real-time polymerase chain reaction was performed
for
Aim. Bone regeneration following the treatment of Staphylococcal bone infection or osteomyelitis is challenging due to the ability of Staphylococcus aureus to invade and persist within bone cells, which could possibly lead to antimicrobial tolerance and incessant bone destruction. Here, we investigated the influence of Staphylococcal bone infection on osteoblasts metabolism and function, with the underlying goal of determining whether Staphylococcus aureus-infected osteoblasts retain their ability to produce extracellular mineralized organic matrix after antibiotic treatment. Method. Using our in vitro infection model, human osteoblasts-like Saos-2 cells were infected with high-grade Staphylococcus aureus EDCC 5055 strain, and then treated with 8 µg/ml rifampicin and osteogenic stimulators up to 21-days. Results. Immunofluorescence and transmission electron microscopic (TEM) imaging demonstrated the presence of intracellular bacteria within the infected osteoblasts as early as 2 hours post-infection. TEM micrographs revealed intact intracellular bacteria with dividing septa indicative of active replication. The infected osteoblasts showed significant amounts of intracellular bacteria colonies and alteration in metabolic activity compared to the uninfected osteoblasts (p≤0.001). Treatment of S. aureus-infected osteoblasts with a single dose of 8 µg/ml rifampicin sufficiently restored the metabolic activity comparative to the uninfected groups. Alizarin red staining and quantification of the rifampicin-treated infected osteoblasts revealed significantly lower amount of mineralized extracellular matrix after 7-days osteogenesis (p<0.05). Interestingly, prolonged osteogenic stimulation and rifampicin-treatment up to 21 days improved the extracellular matrix mineralization level comparable to the rifampicin-treated uninfected group. However, the untreated (native) osteoblasts showed significantly more quantity of mineral deposits (p≤0.001). Ultrastructural analysis of the rifampicin-treated infected osteoblasts at 21-days osteogenesis revealed active osteoblasts and newly differentiated osteocytes, with densely distributed calcium crystal deposits within the extracellular organic matrix. Moreover, residual colony of dead bacteria bodies and empty vacuoles of the fully degraded bacteria embedded within the mineralized extracellular matrix. Gene expression level of prominent bone formation markers, namely RUNX2, COL1A1, ALPL,
Infection is a common complication of severe open fractures and compromises bone healing. The present standard of care is a two-stage approach comprising of initial placement of antibiotic-impregnated PMMA beads to control infection followed later by bone grafting. Although the systemic antibiotics and PMMA/antibiotic beads control the infection initially, there are often residual bacteria within the wound. After grafting and definitive closure, the implanted graft is placed in an avascular defect and could function as a nidus for infection. Bioactive porous polyurethane (PUR) scaffolds have been shown to improve bone healing by delivering recombinant human bone morphogenetic protein-2 (BMP-2) and reduce infection by delivering antibiotics. The release kinetics of the
Background. Current treatments for the prevention of thromboembolism include heparin and low-molecular weight heparins (LMWHs). A number of studies have suggested that long term administration of these drugs may adversely affect osteoblasts and therefore, bone metabolism. Xarelto(tm) (Rivaroxaban) is a new anti-thrombotic drug for the prevention of venous thromboembolism in adult patients undergoing elective hip and knee replacement surgery. The aim of this in vitro study was to investigate the possible effects of rivaroxaban on osteoblast proliferation, function, matrix mineralisation and gene expression compared to enoxaparin, a commonly used LMWH. Methods. Primary human osteoblast cultures were treated with varying concentrations of rivaroxaban (0.013, 0.13, 1.3 and 13 μg/ml) or enoxaparin (0.1, 1.0 and 10 international units/ml). The effect of each drug on osteoblast function and matrix mineralisation was evaluated by measuring alkaline phosphatase activity and calcium deposition, respectively. The MTS assay was used to assess the effect of drug treatments on cell proliferation. Changes in osteocalcin, Runx2 and
Purpose. The aim of this study was to investigate whether growth factors essential for fracture healing are released in the immediate aftermath following fracture and whether reaming of IM cavity causes increased liberation of these autocoids. Methods. Consecutive adult patients with femoral shaft fractures forming two groups (a group who received unreamed nail (n=10) and a second group who received reamed nail (n=10) were recruited for this study. Peripheral blood samples and samples from the femoral canal before and after reaming and before and after the solid nail insertion were collected. Serum was extracted and using Elisa colorimetric assays the concentration of Platelet Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), Insulin-like Growth Factor I (IGF-I) Transforming Growth Factor beta 1 (TGF-. 2. 1) and
Bone morphogenetic proteins (BMPs) are able to induce osteogenic differentiation in many cells, including muscle cells. However, the actual contribution of muscle cells to bone formation and repair is unclear. Our objective was to examine the capacity of myogenic cells to contribute to BMP-induced ectopic bone formation and fracture repair. Osteogenic gene expression was measured by quantitative PCR in osteoprogenitors, myoblasts, and fibroblasts following
Bone is capable of regeneration, and defects often heal spontaneously. However, cartilage, tendon, and ligament injuries usually result in replacement if the site by organized scar tissue, which is inferior to the native tissue. The osteogenic potential of mesenchymal stem cells (MSCs) has already been verified. MSCs hold great potential for the development of new treatment strategies for a host of orthopedic conditions. The multi-lineage potential and plasticity of MSCs allow them to be building blocks for a host of nonhematopoietic tissues, including bone. More recently, several groups have reported on the successful clinical application of tissue engineering strategies in the repair of bony defects in patients secondary to trauma and tumor resection. Advances in fabrication of biodegradable scaffolds that serve as beds for MSC implantation will hopefully lead to better biocompatibility and host tissue integration. Current strategies for bone tissue engineering include the use of osteoconductive matrix devices that promote bony ingrowth, and the delivery of osteoinductive growth factors, including bone morphogenetic protein (BMP) family,
Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting include autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly four types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only
Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately, we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting includes autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly 4 types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only
Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting include autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly 4 types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only
Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately, we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting include autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because they are present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute used was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly four types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only
Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting includes autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly 4 types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only
Purpose. The data regarding the effects of noggin on bone morphogenetic protein (BMP)-induced osteogenesis of mesenchymal stem cells (MSCs) are controversial. Most studies performed in rodent cells/models indicated that noggin was a negative regulator of BMP-2-induced osteogenesis; however, one study conducted with human MSCs in culture showed that the addition of noggin induced osteogenesis in vitro. To clear the controversy, we designed this study to evaluate the effects of knocking down noggin gene expression on BMP-2-induced osteogenesis of human bone marrow-derived primary MSCs in vitro. Method. MSCs were isolated from human tibial bone marrow by density gradient centrifugation. Two noggin small interfering RNAs (siRNAs) were used in this study to knockdown noggin gene expression. There were four study groups: MSCs with no transfection of siRNA (named as NT group), MSCs transfected with non-targeting negative control siRNA (named as control group), MSCs transfected with noggin siRNA1 (named as NOGsi1 group), and MSCs transfected with noggin siRNA2 (named as NOGsi2 group). After transfection, MSCs were induced to undergo osteogenic differentiation by incubating in basal medium containing 0.1 μg/ml
Animal studies examining tendon-bone healing have demonstrated that the overall structure, composition, and organization of direct type entheses are not regenerated following repair. We examined the effect of Low-Intensity Pulsed Ultrasound (LIPUS) on tendon-bone healing. LIPUS may accelerate and augment the tendon-bone healing process through alteration of critical molecular expressions. Eight skeletally mature wethers, randomly allocated to either control group (n=4) or LIPUS group (n=4), underwent rotator cuff surgery following injury to the infraspinatus tendon. All animals were sacrificed 28 days post surgery to allow examination of early effects of LIPUS. Humeral head – infraspinatus tendon constructs were harvested and processed for histology and immunohistochemical staining for BMP2, Smad4, VEGF and RUNX2. All the growth factors were semiquantitative evaluated. T-tests were used to examine differences which were considered significant at p < 0.05. Levene's Test (p < 0.05) was used to confirm variance homogeneity of the populations. The surgery and LIPUS treatment were well tolerated by all animals. Placement of LIPUS sensor did not unsettle the animals. Histologic appearance at the tendon-bone interface in LIPUS treated group demonstrated general improvement in appearance compared to controls. Generally a thicker region of newly formed woven bone, morphologically resembling trabecular bone, was noted at the tendon-bone interface in the LIPUS-treated group compared to the controls. Structurally, treatment group also showed evidence of a mature interface between tendon and bone as indicated by alignment of collagen fibres as visualized under polarized light. Immunohistochemistry revealed an increase in the protein expression patterns of VEGF (p = 0.038), RUNX2 (p = 0.02) and Smad4 (p = 0.05) in the treatment group. There was no statistical difference found in the expression patterns of BMP2. VEGF was positively stained within osteoblasts in newly formed bone, endothelial cells and some fibroblasts at the interface and focally within fibroblasts around the newly formed vessels. Expression patterns of RUNX2 were similar to that of
Currently, there is no animal model in which
to evaluate the underlying physiological processes leading to the heterotopic
ossification (HO) which forms in most combat-related and blast wounds.
We sought to reproduce the ossification that forms under these circumstances
in a rat by emulating patterns of injury seen in patients with severe
injuries resulting from blasts. We investigated whether exposure
to blast overpressure increased the prevalence of HO after transfemoral
amputation performed within the zone of injury. We exposed rats
to a blast overpressure alone (BOP-CTL), crush injury and femoral
fracture followed by amputation through the zone of injury (AMP-CTL)
or a combination of these (BOP-AMP). The presence of HO was evaluated
using radiographs, micro-CT and histology. HO developed in none
of nine BOP-CTL, six of nine AMP-CTL, and in all 20 BOP-AMP rats.
Exposure to blast overpressure increased the prevalence of HO. This model may thus be used to elucidate cellular and molecular
pathways of HO, the effect of varying intensities of blast overpressure,
and to evaluate new means of prophylaxis and treatment of heterotopic
ossification. Cite this article:
Tendinopathy is a debilitating musculoskeletal
condition which can cause significant pain and lead to complete rupture
of the tendon, which often requires surgical repair. Due in part
to the large spectrum of tendon pathologies, these disorders continue
to be a clinical challenge. Animal models are often used in this
field of research as they offer an attractive framework to examine
the cascade of processes that occur throughout both tendon pathology and
repair. This review discusses the structural, mechanical, and biological
changes that occur throughout tendon pathology in animal models,
as well as strategies for the improvement of tendon healing. Cite this article:
