Mineral Component Of Bone Research Articles

Preparation, characterization and mechanical properties of controlled porous gelatin/hydroxyapatite nanocomposite through layer solvent casting combined with freeze-drying and lamination techniques

In this present study, to mimic the mineral and organic component of natural bone, hydroxyapatite (HA) and gelatin (GEL) nanocomposite was prepared via layer solvent casting combined with freeze-drying and lamination techniques. Glutaraldehyde (GA) was used as cross-linking agent. The synthesized nanocrystalline hydroxyapatite and nanocomposite samples were characterized by the commonly used bulk techniques. The results showed that GEL/HA nanocomposite were porous with 3-dimension interconnected microstructure, pore sizes were 100 μm to 1 mm, porosity were 75% to 93% and HA particles are dispersed evenly among gelatin fibers. It was also found that increasing initial GEL concentration and HA content enhance the elastic modulus (E) and reduce toughness and affect pore size and morphology. Finally, the stress–strain behavior in compression was very similar to natural spongy bone where the compressive modulus obtained was about 180 MPa.

Influence of ferutinin on bone metabolism in ovariectomized rats. I: role in preventing osteoporosis

Phytoestrogens play a role in maintaining bone mass in the post-menopausal period for their putative function as osteoprotective agents. The aim of the present study was to investigate the influence of Ferutinin, a phytoestrogen found in the plants of Ferula genus, on bone loss in ovariectomized rats. Such an animal model can simulate the various clinical syndromes deriving from osteoporosis. The effect of the daily oral administration of ferutinin to ovariectomized rats (dosed at 2 mg/kg per day for 30 and 60 days) was compared to that of estradiol benzoate (subcutaneously administered at the dose of 1.5 microg/rat twice a week). After the sacrifice, histomorphometrical analyses were performed on trabecular bone of L4-L5 vertebrae and distal femoral metaphysis, as well as on cortical bone of femoral diaphysis; biochemical parameters (bone mineral components and markers) were also evaluated from the rat serum. The histomorphometrical analyses of trabecular and cortical bone from lumbar vertebrae and femur showed that ferutinin has the same antiosteoporotic effect of estradiol benzoate on bone mass, and in some cases is even stronger. This fact suggests that it could prevent osteoporosis caused by severe estrogen deficiency in ovariectomized rats. The possibility of using ferutinin as an alternative to the commonly employed hormonal replacing therapy in post-menopausal women is discussed.

Clinical, Radiographic and Pathohistological Outcomes of Hydroxyapatite (HAp) Ceramics and Dental Implants in Atrophic Posterior Maxilla

Clinical, Radiographic and Pathohistological Outcomes of Hydroxyapatite (HAp) Ceramics and Dental Implants in Atrophic Posterior Maxilla Introduction. Implant based prosthodontic rehabilitation of patients with atrophic edentulous posterior maxilla has necessity in reinforcement of alveolar bone using different bone substitutes. It is important to evaluate late outcomes in integration of synthetic HAp as biomaterial in chemical composition close to main natural bone mineral component in elevated maxillary sinus floor and osseointegration of dental implants. Aim of the study. To evaluate clinical and radiological outcomes of one stage maxillary sinus floor augmentation with synthetic HAp granules and dental implant insertion, mineralization degree of residual bone and augmented sinus part, morphological analysis of biopsies from HAp/host tissue hybrid and residual alveolar bone was performed. Materials and methods. One stage maxillary sinus floor elevation with synthetic HAp granules and 147 SEMADOS (BEGO) dental implant insertions in 70 patients were included in this study. Clinical and radiograph analyzes by dental X-rays, digital orthopantomogramms, quantitative radiodensitometry after 3 and 5 years was done. Trephine biopsies of residual alveolar bone and elevated part of maxillary sinus 6 months after implantation was done in 30 cases. Results. During this period 6 implants (4.2%) were lost. We found the decrease of radiodensity in HAp augmentated maxillary sinus area and increase of radiodensity in the area of residual alveolar bone. In biopsies after 6 months biomaterial/host tissue hybrid consisted of small bone trabecules, fibrous tissue and granules of irregular shape without inflammatory cells. Slow degradation of HAp granules by activity of osteoclast like macrophages was observed. Conclusions. Osseointegration was lost in 4.2% of inserted in augmented maxillary sinus implants. Radiodensitometry showed decrease of optical density in augmented sinus part and increase in residual alveolar bone. In biopsies of host tissue/biomaterial hybrid was bone newformation, connective tissue and biodegradation of HAp granules by osteoclast like cells.

Macroporous Calcium Phosphate Bioceramics as Drug Release Agents: A Kinetics Study of Ampicillin Release

Semi-synthetic beta-lactam antibiotics are the most important class of antibacterial agents. Their use in veterinary and human medicine is in continuous expansion. Calcium phosphate bioceramics have been used in medicine and dentistry for nearly 30 years. Calcium phosphate ceramics (CPC) are nowadays being widely used as drug delivery systems because of their desirable properties such as biocompatibility, bioresorbability, controlled release etc. In recent years In this work, kinetic models to describe ampicillin adsorption from CPC were investigated. Calcium phosphate bioceramic are analogous to the mineral component of bones, its properties make it suitable for implant materials and delivery agents of drugs

First-principles study of hydroxyapatite surfaces and water adsorption

Hydroxyapatite (HA) is the main mineral component of natural bone and an important synthetic biomaterial. The surfaces of this material are critical as the biological action takes place at the interface between the HA and the biological medium. Ab initio total energy methods are used to study the atomic structure and surface chemistry of HA. Low index HA surfaces in vacuum, the adsorption of water on these surfaces, and the loss of Ca from them are considered. All surfaces are found to react strongly with water, and after adsorption of water (001) and Ca-rich (010), surfaces are found to be energetically favored. The loss of Ca from the surface in exchange for two H is also very favorable. The calculated energies of the various surfaces shed light on the morphologies of HA crystallites found in dissolution studies.

Recommendations for the assessment and monitoring of skeletal manifestations in children with Gaucher disease

Gaucher disease (GD), the most common of the lysosomal storage disorders, results from mutations in the gene for acid β-glucosidase (glucocerebrosidase, GBA) leading to insufficient enzyme activity [1]. Glucocerebroside accumulation in the lysosomes of various cell types is responsible for the clinical manifestations of GD, which may include hepatomegaly, splenomegaly, anemia, thrombocytopenia, and bone marrow infiltration by lipid-engorged “Gaucher cells.” Occurring panethnically, type 1 (non-neuronopathic) is the most prevalent form of GD, while the less frequent type 2 (acute neuronopathic) and type 3 (chronic neuronopathic) are characterized by neurological involvement. More than half of type 1 patients are diagnosed in childhood and an earlier age of onset is indicative of more severe disease due to its progressive nature. Affecting both the marrow and mineral compartments, GD-related bone disease is the most significant cause of morbidity and long-term disability for patients. GD-related bone disease in children is a major cause for concern as it puts them at risk of developing irreversible and debilitating bone complications and interferes with normal growth and achievement of optimal bone mass during a critical period of growth. Timely initiation of appropriate disease management is necessary to avoid serious long-term complications such as growth retardation, osteoporosis, and fractures, and includes an initial radiological assessment and ongoing monitoring of both the bone marrow and mineral components. General guidelines for the monitoring of skeletal disease in children with type 1 GD recommend magnetic resonance imaging (MRI) of the spine and femora; radiography of the spine (when clinically indicated), chest, pelvis, and long bones; and dual-energy X-ray absorptiometry (DXA) of the spine and hips at baseline and every 12–24 months [2, 3]. However, these recommendations require further clarification in view of the challenges associated with their use in children with GD, especially since the use of conventional radiography is limited by a high burden of radiation and lack of sensitivity and specificity. The current standard of care for type 1 GD is enzyme replacement therapy (ERT) with imiglucerase (Cerezyme®; Genzyme Corporation, Cambridge, MA, USA). Oral substrate reduction therapy with miglustat (Zavesca®; Actelion, San Francisco, CA, USA) is also available for the treatment of patients with mild to moderate GD for whom ERT is not an option. The availability of therapy that may prevent or reverse GD-related bone disease heightens the need for early diagnosis and initiation of disease management in children. A Working Group of international experts met in October 2006 to recommend evidence- and consensus-based guidelines to facilitate the assessment and monitoring of bone disease in children with type 1 or type 3 GD.

Correlation between Hydroxyapatite Crystallite Orientation and Ultrasonic Wave Velocities in Bovine Cortical Bone

The mineral component of bone is mainly composed of calcium phosphate, constituting 70% of total bone mass almost entirely in the form of hydroxyapatite (HAp) crystals. HAp crystals have a hexagonal system and uniaxial elastic anisotropy. The objective of this study was to investigate the effect of HAp crystallite preference on macroscopic elasticity. Ultrasonic longitudinal wave velocity and the orientation of HAp crystallites in bovine cortical bone are discussed, considering microstructure, density, and bone mineral density (BMD). Eighty cube samples of cortical bone were made from two bovine femurs. The orientation of HAp crystallites was evaluated by integrated intensity ratio of (0002) peak using an X-ray diffractometer. Ultrasonic longitudinal wave velocity was investigated with a conventional pulse system. The intensity ratio of HAp crystallites and velocity were measured in three orthogonal directions; most HAp crystallites aligned in the axial direction of the femurs. Our results demonstrate a linear correlation between velocity and intensity ratio in the axial direction. Significant correlation between velocity and BMD values was observed; however, the correlation disappeared if we focused on the identical type of microstructure. In conclusion, differences in microstructure type have an impact on density and BMD, which clearly affects the velocity. In addition, at the nanoscopic level, HAp crystallites aligned in the axial direction also affected the velocity and anisotropy.

Proteome analysis of matrix vesicles isolated from femurs of chicken embryo

Matrix vesicles (MVs) are extracellular organelles that initiate mineral formation, accumulating inorganic phosphate (P(i)) and calcium leading to the formation of hydroxyapatite (HA) crystals, the main mineral component of bones. MVs are produced during bone formation, as well as during the endochondral calcification of cartilage. MVs are released into the extracellular matrix from osseous cells such as osteoblasts and hypertrophic chondrocytes. In this report, using 1-D SDS-PAGE, in-gel tryptic digestion and an LC-MS-MS/MS protein identification protocol, we characterized the proteome of MVs isolated from chicken embryo (Gallus gallus) bones and cartilage. We identified 126 gene products, including proteins related to the extracellular matrix and ion transport, as well as enzymes, cytoskeletal, and regulatory proteins. Among the proteins recognized for the first time in MVs were aquaporin 1, annexin A1 (AnxA1), AnxA11, glycoprotein HT7, G(i) protein alpha2, and scavenger receptor type B. The pathways for targeting the identified proteins into MVs and their particular functions in the biomineralization process are discussed. Obtaining a knowledge of the functions and roles of these proteins during embryonic mineralization is a prerequisite for the overall understanding of the initial mineral formation mechanisms.

Ligand-Modified Aminobisphosphonate for Linking Proteins to Hydroxyapatite and Bone Surface

An increase in bone resorption is one of the main symptoms of osteoporosis, a disease that affects more and more individuals every day. Bisphosphonates are known to inhibit bone resorption and thus are being used as a treatment for osteoporosis. Aminobisphosphonates present a functionality that can be easily used for conjugation to other molecules, such as peptides, proteins, and ligands for protein recognition. In this study, an aminobisphosphonate conjugated with biotin was used as a model linker for protein attachment to bone. With this system, the interaction of biotinylated aminobisphosphonate with hydroxyapatite, a major mineral component of bone, was investigated. Quantification of the binding of aminobisphosphonate to hydroxyapatite was performed using a fluorescently labeled antibody for biotin. Additionally, the interaction of the biotinylated aminobisphosphonate with multiple treatments of cortical bone from the midshaft of a cow femur was studied. It was demonstrated that modified aminobisphosphonate reagents can bind hydroxyapatite and bone at high levels, while the biotin functionality is free to be recognized by the fluorescently labeled antibiotin antibody, suggesting that modified aminobisphosphonates could be used to link other peptides or proteins to the bone surface.

Recombinant expression of mouse osteocalcin protein in Escherichia coli

Osteocalcin is the most abundant non-collagenous protein of bone. Recombinant mouse osteocalcin protein (mOC) that includes the highly conserved central domain for binding to hydroxyapatite (HA), a mineral component of bone, was expressed in Escherichia coli. Purified mOC protein exhibited a significant increase in HA adhesion and differentiation in osteoblast cells as well as binding to HA with high affinity.

Hard-templating synthesis of a novel rod-like nanoporous calcium phosphate bioceramics and their capacity as antibiotic carriers

Calcium phosphate ceramics analogous to the mineral component of bones, their biocompatibility and osteoconductive properties make them desirable as implant materials and delivery agents of drug and DNA molecules. Here we report a hard-templating synthesis of nanoporous calcium phosphate ceramics, which is based on filling the calcium and phosphorus sources into the nanospaces of rod-like ordered mesoporous carbon (CMK-3). The removal of the carbon template by combustion leads to rod-like nanoporous calcium phosphate bioceramics. They have disordered three-dimensional (3D) interconnected nanopores with diameter of 20–30 nm. The wall thickness is approximately 20–30 nm. Based on nitrogen sorption isotherms, the pore size, surface area and pore volume of this material is ∼30 nm, 27 m 2 g −1 and 0.27 cm 3 g −1, respectively. Wide-angle XRD and IR measurements reveal that the inorganic walls of products consist of highly crystalline calcium phosphates with main hydroxyapatite phases. In antibiotic charging experiments, these nanoporous bioceramics show a much higher charging capacity (1621 μg g −1) than that of commercially available calcium phosphate (100 μg g −1), which does not have any nanoporosity.

Characterization of Surface Biocompatibility of Crystallographically Aligned Hydroxyapatite Fabricated Using Magnetic Field

Hydroxyapatite (HAp) is the main mineral component of bone and is used as a raw material for artificial bones and teeth, and as an adsorbent in liquid chromatography, among its other uses. As a result of its anisotropic crystal structure, HAp shows adsorption behavior that depends on the crystal plane. However, the differences between the a-plane and the c-plane of the HAp crystal in terms of their bioactivity, cellpropagation behavior, etc., have not yet been fully clarified. In this study, we fabricated highly crystallographically aligned samples of HAp by using a 10-T magnetic field, and we studied the effects of the specific crystal plane of HAp on its bioactivity by immersing the samples in a simulated body fluid. HAp is precipitated on both a-plane- and c-plane-aligned HAp sample surfaces. The rate of precipitation on a HAp sample immersed in the simulated body fluid depended on the crystal plane, especially during the first 24 h of immersion. Because the rate of precipitation on the c-plane is faster than on the a-plane, HAp is precipitated preferentially on the c-plane during the early stages of precipitation. [doi:10.2320/matertrans.MI200712]

Radiesse for Aesthetic Soft Tissue Augmentation

Introduction: Calcium hydroxyapatite (CaHa; also spelled “hydroxylapatite”) is the main mineral component of bone, calcified cartilage, and teeth. It has been used since the 1970s in many specialties, including orthopedics, urology, otolaryngology, maxillofacial surgery, and radiology, as a bioactive implant that promotes chemical attachment of the soft tissue to its surface. In 2001, Radiance FN (now Radiesse) was introduced as a CaHa-based product and approved by the US Food and Drug Administration (FDA) as a radiographic tissue marker, for soft tissue vocal fold augmentation, and for implants in maxillofacial defects. Currently, it is also used outside the United States and off-label in the United States for facial soft tissue augmentation. Microspheres of CaHa are suspended in a mixture of water, glycerin, and carboxymethylcellulose gel that provides a scaffold for tissue infiltration. Once injected, the gel is degraded and the CaHa infiltrates the surrounding cells. CaHa is nonirritating, and the carrier gel components are classified as safe by the FDA. Although a great variety of fillers are currently on the market, CaHa (Radiesse) has demonstrated the longest duration in tissue without any reports of antigenicity, migration, or granuloma formation. In this study, we report our experience with CaHa (Radiesse) for aesthetic soft tissue augmentation. Materials and Methods: A total of 139 patients were treated over an 18-month period at 2 private offices in Argentina and the United States. Exclusion criteria included previous use of permanent tissue fillers in the treatment area. Patients with previous use of hyaluronic acid fillers in the treatment area (up to 1 year prior to the study) were allowed to participate in the study. Radiesse was injected from 1-mL prefilled syringes with 27½-gauge needles in different areas such as nasolabial folds, lips, marionettes lines, cheeks, and cellulite dimples. Patient satisfaction and adverse effects were assessed by both physicians and patients during the procedure and during follow-up visits up to 1 year later. Results: Minimal pain, erythema, edema, and bruising were noted during and immediately after the procedure. All of the patients treated were satisfied with their results after one visit. There were no long-term adverse effects during the study period or on follow-up visits. Evaluation of 75% of the patients 1 year after treatment revealed persistence of filling effects. Discussion: CaHa used for aesthetic soft tissue augmentation yields immediate clinical results with high patient satisfaction.

Solubility of Structurally Complicated Materials: II. Bone

Bone is a structurally complex material, formed of both organic and inorganic chemicals. The organic compounds constitute mostly collagen and other proteins. The inorganic or bone mineral components constitute predominantly calcium, phosphate, carbonate, and a host of minor ingredients. The mineralized bone is composed of crystals which are closely associated with a protein of which collagen is an acidic polysaccharide material. This association is very close and the protein integrates into the crystalline structure. The mineralization involves the deposition of relatively insoluble crystals on an organic framework. The solubility process takes place when the outermost ions in the crystal lattice breakaway from the surface and become separated from the crystal. This is characteristic for ions dissolving in water or aqueous solutions at the specified temperature. The magnitude of solubility is temperature and pH dependent. Bone is sparingly soluble in most solvents. Enamel is less soluble than bone and fluoroapatite is the least soluble of all apatites in acid buffers. Collagen is less soluble in neutral salt solution than in dilute acid solutions at ambient temperatures. The solubility of collagens in solvents gradually decreases with increasing age of the bone samples.

Homonuclear and Heteronuclear NMR Studies of a Statherin Fragment Bound to Hydroxyapatite Crystals

Acidic proteins found in mineralized tissues act as nature's crystal engineers, where they play a key role in promoting or inhibiting the growth of minerals such as hydroxyapatite (HAP), Ca10(PO4)6(OH)2, the main mineral component of bone and teeth. Key to understanding the structural basis of protein-crystal recognition and protein control of hard tissue growth is the nature of interactions between the protein side chains and the crystal surface. In an earlier work we have measured the proximity of the lysine (K6) side chain in an SN-15 peptide fragment of the salivary protein statherin adsorbed to the Phosphorus-rich surface of HAP using solid-state NMR recoupling experiments. 15N{31P} rotational echo double resonance (REDOR) NMR data on the side-chain nitrogen in K6 gave rise to three different models of protein-surface interaction to explain the experimental data acquired. In this work we extend the analysis of the REDOR data by examining the contribution of interactions between surface phosphorus atoms to the observed 15N REDOR decay. We performed 31P-31P recoupling experiments in HAP and (NH4)2HPO4 (DHP) to explore the nature of dipolar coupled 31P spin networks. These studies indicate that extensive networks of dipolar coupled 31P spins can be represented as stronger effective dipolar couplings, the existence of which must be included in the analysis of REDOR data. We carried out 15N{31P} REDOR in the case of DHP to determine how the size of the dephasing spin network influences the interpretation of the REDOR data. Although use of an extended 31P coupled spin network simulates the REDOR data well, a simplified 31P dephasing system composed of two spins with a larger dipolar coupling also simulates the REDOR data and only perturbs the heteronuclear couplings very slightly. The 31P-31P dipolar couplings between phosphorus nuclei in HAP can be replaced by an effective dipolar interaction of 600 Hz between two 31P spins. We incorporated this coupling and applied the above approach to reanalyze the 15N{31P} REDOR of the lysine side chain approaching the HAP surface and have refined the binding models proposed earlier. We obtain 15N-31P distances between 3.3 and 5 A from these models that are indicative of the possibility of a lysine-phosphate hydrogen bond.

Effect of reinforcement particle size on in vitro behavior of β‐tricalcium phosphate‐reinforced high‐density polyethylene: A novel orthopedic composite

Beta-tricalcium phosphate-reinforced high-density polyethylene (beta-TCP/HDPE) is a new biomaterial, which was made to simulate bone composition and study its capacity to act like bony tissues. This material was produced by replacing mineral component and collagen soft tissue of bone with beta-TCP and HDPE, respectively. The biocompatibility of composite samples with different volume fractions of TCP (20, 30, and 40 vol %) and two different particle sizes (80-100 and 120-140 mesh size) was examined in vitro using the osteoblast cell line G-292 by proliferation, alkaline phosphatase (ALP) production, and cell adhesion assays. Cell-material interaction on the surface of the composites was observed by scanning electron microscopy (SEM). The effect of beta-TCP particle size on behavior of the osteoblast cell line was compared between two groups of the composite samples containing smaller and larger reinforcement particle sizes as well as with those of a negative control. In general, results showed that the composite samples containing larger particles supported a higher rate of proliferation and ALP production by osteoblast cells after 3, 7, and 14 days of incubation compared to the composite samples with smaller particle size and control. Furthermore, more cells were attached to the surface of composite samples containing larger particle size when compared to the smaller particle size composites (p<0.05). This number was nearly equal with numbers adhered on negative control [tissue culture polystyrene (TPS)] and significantly higher in comparison with composite control [polyethylene (PE)] (p<0.05). Adhered cells presented a normal morphology by SEM and many of the cells were seen to be undergoing cell division. These findings indicate that beta-TCP/HDPE composites are biocompatible, nontoxic, and in some cases, act to stimulate proliferation of the cells, ALP production, and cell adhesion when compared to the control counterparts. Furthermore, beta-TCP/HDPE samples with larger reinforcement particle size were shown to possess better biological properties.

A Solid-State NMR Study of the Dynamics and Interactions of Phenylalanine Rings in a Statherin Fragment Bound to Hydroxyapatite Crystals

Extracellular matrix proteins regulate hard tissue growth by acting as adhesion sites for cells, by triggering cell signaling pathways, and by directly regulating the primary and/or secondary crystallization of hydroxyapatite, the mineral component of bone and teeth. Despite the key role that these proteins play in the regulation of hard tissue growth in humans, the exact mechanism used by these proteins to recognize mineral surfaces is poorly understood. Interactions between mineral surfaces and proteins very likely involve specific contacts between the lattice and the protein side chains, so elucidation of the nature of interactions between protein side chains and their corresponding inorganic mineral surfaces will provide insight into the recognition and regulation of hard tissue growth. Isotropic chemical shifts, chemical shift anisotropies (CSAs), NMR line-width information, (13)C rotating frame relaxation measurements, as well as direct detection of correlations between (13)C spins on protein side chains and (31)P spins in the crystal surface with REDOR NMR show that, in the peptide fragment derived from the N-terminal 15 amino acids of salivary statherin (i.e., SN-15), the side chain of the phenylalanine nearest the C-terminus of the peptide (F14) is dynamically constrained and oriented near the surface, whereas the side chain of the phenylalanine located nearest to the peptide's N-terminus (F7) is more mobile and is oriented away from the hydroxyapatite surface. The relative dynamics and proximities of F7 and F14 to the surface together with prior data obtained for the side chain of SN-15's unique lysine (i.e., K6) were used to construct a new picture for the structure of the surface-bound peptide and its orientation to the crystal surface.

Cerâmicas bioativas: estado da arte

Bioactive glasses undergo corrosion with leaching of alkaline ions when exposed to body fluids. This results in the spontaneous formation of a layer of hydroxyapatite (HA), the mineral component of natural bone, which in turn can induce bone growth in vivo. This paper describes the different types of bioactive glasses, the characterization methods currently used, and the main factors that influence their bioactivity. Nucleation and crystallization, the main mechanisms involved in the formation of hydroxyapatite, Ca10(PO4)6(OH)2, are discussed as a function of the chemical composition and the reactivity of the surface of the material. Finally, promising applications are considered.

First Principles Investigation of Mineral Component of Bone: CO3 Substitutions in Hydroxyapatite

First principles calculations are used to investigate carbonated hydroxyapatite, a naturally occurring mineral and also the inorganic component of animal bone. Two types of carbonate substitution are studied: A-type in which the carbonate ion substitutes for an OH and B-type where the substitution is for a phosphate. Both types have unbalanced charges and various forms of charge compensation are treated. The methods, which are based on density functional theory and first principles pseudopotentials, yield equilibrium atomic arrangements, changes in lattice parameters, and total energies for different types of substitution. When calculated energies of selected stable compounds are used, the formation energies of different carbonate substitutions with accompanying charge compensation defects can be compared. The results indicate that compact complexes are energetically favored, and a B-type material with charge compensation by a calcium vacancy together with a hydrogen atom which bonds to a neighboring phosphate is the most stable of all those considered.

Development and application of bone morphogenetic proteins for the enhancement of bone healing

Bone morphogenetic proteins are multifunctional cytokines and members of the transforming growth factor-β superfamily. They include the only signaling molecules that can singly induce de novo bone formation at orthotopic and heterotopic sites. Their osteoinductive potency and ability to enhance or accelerate bone healing has been demonstrated in animal models of human orthopedic injuries and diseases, and in human clinical orthopedic patients. Recombinant human bone morphogenetic proteins 2 and 7 have recently received the approval of regulatory agencies for the clinical treatment of selected human acute long bone fractures and nonunions, as well as lumbar fusion. It is likely that additional indications will be approved as supportive data for the proteins’ efficacy in the treatment of specific orthopedic conditions are generated. In addition to the type I collagen presently being used clinically as a locally implantable delivery vehicle for bone morphogenetic proteins, mineral, synthetic polymer, and extracellular matrix components continue to be tested as alternative matrices. Other means of bone morphogenetic protein delivery undergoing preliminary evaluation include gene transfer therapy and systemic administration.