Production Of New Bone Research Articles

DKK-1 in psoriatic arthritis: Correlation with disease activity and enthesopathy

BackgroundPsoriatic arthritis (PsA) is a complex inflammatory disease with varied clinical characteristics. A pathognomonic characteristic of PsA is enthesitis. Entheseal inflammation ultimately leads to the production of new bone (enthesophytes). Dickkopf-related protein-1 (DKK-1) is a wingless (Wnt) inhibitor that inhibits osteoblast function. ObjectivesAssessment of the serum level of DKK-1 and its association with disease activity and enthesopathy in PsA patients. MethodsThis observational case–control study included 50 PsA patients and 50 healthy volunteers matched for age and gender. All participants were subjected to full medical history, clinical assessment, PSA activity using Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the severity and extent of psoriasis were determined by the Psoriasis Area and Severity Index (PASI). Ultrasonographic assessment of the entheses was done in accordance with the Madrid Sonographic Enthesitis Index (MASEI). Serum level of DKK-1 and correlation with disease activity and enthesopathy in PsA patients were assessed. ResultsThere was no significant difference between patients and controls regarding age and sex. The mean value of SPARCC index, DAPSA score and PASI score were 6.74±4.58, 33.24±15.26, and 8.35±10.93, respectively. There was significant difference between patients and controls regarding the serum levels of DKK-1 and MASEI score (p<0.0001). There was a significant positive correlation between serum DKK-1 and MASEI (r: 0.43527, p: 0.00158), MASEI inflammatory (r: 0.37958, p: 0.00655), and MASEI damage (r: 0.38384, p: 0.00593). ConclusionsSerum DKK-1 levels were elevated in PsA patients and were found to be correlated with MASEI score for enthesopathy.

DKK-1 in psoriatic arthritis: Correlation with disease activity and enthesopathy

BackgroundPsoriatic arthritis (PsA) is a complex inflammatory disease with varied clinical characteristics. A pathognomonic characteristic of PsA is enthesitis. Entheseal inflammation ultimately leads to the production of new bone (enthesophytes). Dickkopf-related protein-1 (DKK-1) is a wingless (Wnt) inhibitor that inhibits osteoblast function. ObjectivesAssessment of the serum level of DKK-1 and its association with disease activity and enthesopathy in PsA patients. MethodsThis observational case–control study included 50 PsA patients and 50 healthy volunteers matched for age and gender. All participants were subjected to full medical history, clinical assessment, PSA activity using Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the severity and extent of psoriasis were determined by the Psoriasis Area and Severity Index (PASI). Ultrasonographic assessment of the entheses was done in accordance with the Madrid Sonographic Enthesitis Index (MASEI). Serum level of DKK-1 and correlation with disease activity and enthesopathy in PsA patients were assessed. ResultsThere was no significant difference between patients and controls regarding age and sex. The mean value of SPARCC index, DAPSA score and PASI score were 6.74±4.58, 33.24±15.26, and 8.35±10.93, respectively. There was significant difference between patients and controls regarding the serum levels of DKK-1 and MASEI score (p<0.0001). There was a significant positive correlation between serum DKK-1 and MASEI (r: 0.43527, p: 0.00158), MASEI inflammatory (r: 0.37958, p: 0.00655), and MASEI damage (r: 0.38384, p: 0.00593). ConclusionsSerum DKK-1 levels were elevated in PsA patients and were found to be correlated with MASEI score for enthesopathy.

HISTOLOGICAL STUDY TO COMPARE THE APPROPRIATE PARTICLE SIZE OF BETA TCP FOR SOCKET PRESERVATION

Background: One the most used and potent synthetic bone graft substitute which is not only osteoconductive, but also osteoinductive which has been recently discovered and gain popularity is the β-tricalcium phosphate (β-TCP). Along with its cell-mediated resorption propertybeta TCP allow regeneration of full bone defect. Its clinical outcome is sometimes considered to be “unpredictable”, possibly due to a poor understanding of β-TCP physico-chemical properties. Histological evaluation and effects of of bet AIM: a TCP small and large particle at the site of defect in cases of grossly decayed teeth, bone defect and other required areas. Total of 20 cases we Material and Methods: re included in the study (10 cases each of small and large particle). Trephine biopsy was performed and sent for histological evaluation. Histological evaluation depicted the results Results: on the basis of new none formation with residual bone graft material. Vascularity is studied in both the cases with areas of inammation. Conclusion: Production of Mesenchymal stem cells progenitors plays a potent role in elucidating the effects of small Beta TCP particle and is responsible for the production of new bone.

Effect of Injectable platelet-rich fibrin (i-PRF) on new bone formation in surgical expansion with mini-screw assisted rapid palatal expander: A dog model study

The objective of the study is to test whether the local injection of i-PRF may affect osteoblast, blood vessels and new bone formation in surgically expanded mid palatal suture using maxillary skeletal expander.Eighteen adult male local breed dogs were divided randomly into three groups: group I (control), includes the expansion with maxillary skeletal expander that was done without corticotomy and i-PRF. Group II, involves the expansion that was done with mid palatal corticotomy but without i-PRF injection. Group III, has the expansion that was done with mid palatal corticotomy and has injection with 2 ml of i-PRF. Each group consisted of 6 dogs which were subdivided into 3 dogs. Three dogs were sacrificed after 15 days and the other 3 dogs were sacrificed after 45 days. The number of osteoblast, blood vessels and new bone formation percentage were statistically analyzed using Sigma plot platform. Mean and standard error, ANOVA and Duncan were performed among the different groups. Values of P ≤ 0.05 were considered significant.After expansion, the i-PRF group demonstrated a considerable increase in the amount of new bone in the mid-palatal suture at 15 and 45 days compared with other 2 groups which were indicated by highest percentages of new bone formation (29.30% of 15 days and 76.55% at 45 days) if compared to control group which were (7.72% at 15 days and 22.30% at 45 days). The corticotomy groups were in between, 15.33% and 46.84% respectively. Moreover the number of osteoblasts was higher in corticotomy with i-PRF group on 15 days and decreased on 45 days than the other two groups, while the blood vessels were highest in this group than the other two groups both on 15 and 45 days.I-PRF enhanced the production of osteoblast, blood vessels, and new bone in the surgically expanded mid palatal suture.

Optimizing Design Parameters of PLA 3D-Printed Scaffolds for Bone Defect Repair

Current materials used to fill bone defects (ceramics, cement) either lack strength or do not induce bone repair. The use of biodegradable polymers such as PLA may promote patient healing by stimulating the production of new bone in parallel with a controlled degradation of the scaffold. This project aims to determine the design parameters maximising scaffold mechanical performance in such materials. Starting from a base cylindrical model of 10 mm height and of outer and inner diameters of 10 and 4 mm, respectively, 27 scaffolds were designed. Three design parameters were investigated: pore distribution (crosswise, lengthwise, and eccentric), pore shape (triangular, circular, and square), and pore size (surface area of 0.25 mm2, 0.5625 mm2, and 1 mm2). Using the finite element approach, a compressive displacement (0.05 mm/s up to 15% strain) was simulated on the models and the resulting scaffold stiffnesses (N/mm2) were compared. The models presenting good mechanical behaviors were further printed along two orientations: 0° (cylinder sitting on its base) and 90° (cylinder laying on its side). A total of n = 5 specimens were printed with PLA for each of the retained models and experimentally tested using a mechanical testing machine with the same compression parameters. Rigidity and yield strength were evaluated from the experimental curves. Both numerically and experimentally, the highest rigidity was found in the model with circular pore shape, crosswise pore distribution, small pore size (surface area of 0.25 mm2), and a 90° printing orientation. Its average rigidity reached 961 ± 32 MPa from the mechanical testing and 797 MPa from the simulation, with a yield strength of 42 ± 1.5 MPa. The same model with a printing orientation of 0° resulted in an average rigidity of 515 ± 7 MPa with a yield strength of 32 ± 1.6 MPa. Printing orientation and pore size were found to be the most influential design parameters on rigidity. The developed design methodology should accelerate the identification of effective scaffolds for future in vitro and in vivo studies.

Craniomandibular osteopathy in dog – clinical and radiographic aspects

Cranio-mandibular osteopathy is an idiopathic cranian hyperostosis condition, self-limiting, affecting young growing canines up to one year of age. This condition is characterized by the production of new bone, with an irregular appearance and symmetrical distribution, usually affecting the mandible, possibly extending to the temporomandibular joint and/‌or tympanic bulla. The clinical presentation and imaging findings are variable, depending on the bones involved and the severity of the new bone production. The information regarding the breed and age of the patient, in conjunction with imaging aspects regarding the appearance and location of cranian hyperostosis, are sufficient data to establish the diagnosis. The prognosis depends on the bones involved and the severity of new bone production, and the treatment aims at reducing prehension and mastication disorders caused by the development of hyperostosis, as well as ensuring the patient’s nutritional support.

Calvarial hyperostosis syndrome in the dog

Calvarial hyperostosis syndrome is a proliferative, non-neoplastic, self-limiting osteopathy characterized by a production of new bone at the flat bones of the skull (frontal and parietal). This condition occurs in young dogs, up to 1 year old, most of the cases presented in the literature belong to the Bullmastiff breed, but the disease also affects other breeds. Clinical signs and imaging findings, supplemented by histological examination, provide important information for establishing a diagnosis. Usually, the prognosis is favorable and the recommended treatment is symptomatic.

The effect of orthodontic extrusion on alveolar bone - a prospective clinical study

Introduction/Objective. Orthodontic extrusion is the procedure for moving the teeth in a vertical, coronal direction. This movement induces changes in the periodontal ligament and the production of new alveolar bone. The objective of the study was to determine the changes on buccal, palatal and interdental alveolar bone as a result of orthodontic extrusion. Methods. Experimental group included six patients who received orthodontic treatment with the fixed appliances; the control group included four patients without orthodontic treatment. Two cone-beam computed tomography scans (initial and final) were obtained for each patient in both groups. Length of a tooth, shortest distance from tooth?s center of resistance to the referent plane, distance from buccal or palatal plate tip to the enamel-cement junction, the height of interdental septum, buccal and palatal plate vertical gain, buccal and palatal plate thicknesses were measured on initial and final scan in the experimental and control group. Results. The reduced length of the extruded tooth was observed in the experimental group. The distance from buccal and palatal plate tip to the enamel-cement junction, mesial interproximal bone septum and buccal plate gain significantly increased in the experimental group. No significant difference was found in the distal interproximal bone septum, palatal plate gain and buccal/palatal plate thickness between groups. Conclusion. Orthodontic extrusion affects alveolar bone level by gaining the hard tissue buccal and mesial of extruded teeth, while buccal and palatal plate thickness insignificantly changed.

The Bone Extracellular Matrix in Bone Formation and Regeneration.

Bone regeneration repairs bone tissue lost due to trauma, fractures, and tumors, or absent due to congenital disorders. The extracellular matrix (ECM) is an intricate dynamic bio-environment with precisely regulated mechanical and biochemical properties. In bone, ECMs are involved in regulating cell adhesion, proliferation, and responses to growth factors, differentiation, and ultimately, the functional characteristics of the mature bone. Bone ECM can induce the production of new bone by osteoblast-lineage cells, such as MSCs, osteoblasts, and osteocytes and the absorption of bone by osteoclasts. With the rapid development of bone regenerative medicine, the osteoinductive, osteoconductive, and osteogenic potential of ECM-based scaffolds has attracted increasing attention. ECM-based scaffolds for bone tissue engineering can be divided into two types, that is, ECM-modified biomaterial scaffold and decellularized ECM scaffold. Tissue engineering strategies that utilize the functional ECM are superior at guiding the formation of specific tissues at the implantation site. In this review, we provide an overview of the function of various types of bone ECMs in bone tissue and their regulation roles in the behaviors of osteoblast-lineage cells and osteoclasts. We also summarize the application of bone ECM in bone repair and regeneration. A better understanding of the role of bone ECM in guiding cellular behavior and tissue function is essential for its future applications in bone repair and regenerative medicine.

The Important Role and Implications of Citrate in the Composition, Structure, and Function of Oral/Periodontal/Craniofacial Tissues.

High citrate concentration is a major component in the structure of craniofacial bone, teeth and periodontal tissues of humans and other osteovertebrates. It is now established that citrate incorporation into the apatite/collagen complex of bone is essential for the manifestation of the important biomechanical properties of bone; such as stability, strength, and resistance to fracture. The osteoblasts are specialized citrate-producing cells that provide the citrate incorporated in bone during osteogenic stem cell differentiation for production of new bone; “citration” that occurs in concert with mineralization. Dentin and cementum contain high citrate levels; as contrasted with low citrate in enamel. There exists no information regarding the status and source of incorporated citrate in dentin or in cementum. These are important issues relating to oral, periodontal, craniofacial structures. For example, repair of defects should include new tissue that exhibits the composition, structure, and biomechanical properties of the “normal” tissue; which cannot be achieved in the absence of citrate incorporation in the new tissues. Unfortunately, the presence and role of citrate in these tissues have been largely ignored and unrecognized over the past about 40 years by the dental and medical community. The intent of this review is to re-establish the interest and research regarding the important citrate relationships and issues; with focus on related interests in dentistry.

Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway.

Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline phosphatase and osteocalcin gene expressions. Our results suggest the potential of chitosan nanofiber scaffolds for therapy of bone diseases, including bone defects and bone fractures.

Posterior cranial vault distraction osteogenesis: evolution of technique.

The rapid growth of the brain in the first few years of life drives the expansion of the cranial vault. This expansion occurs primarily at the cranial sutures; premature fusion of these results in growth restriction perpendicular to the axis of the suture. The result of this is physical deformation of the cranial and facial skeleton, as well as the distortion of the underling brain and its physiology. These patients can present with symptoms of raised intracranial pressure, neurodevelopmental delay, as well as the morphological features of craniosynostosis. Acquired conditions such as the slit ventricle syndrome may also result in cephalocranial disproportion with these clinical features. Traditional vault remodeling surgery is able to correct the physical abnormalities as well as correcting cephalocranial disproportion. Its limitations include the degree of scalp expansion achievable as well as resulting defects in the bone. The use of distraction osteogenesis of the cranial vault permits a controlled expansion in a predetermined vector in a gradual manner. When used in the calvarium, this combines the benefits of tissue expansion on the scalp, as well as stimulating the production of new bone, reducing the defects resulting from expansion. In this review, the authors describe some of the surgical considerations important to the use of this technique. This includes the relevant anatomy and technical aspects illustrated with the use of clinical cases. Finally, they present a summary of their experience and discuss the complications associated with cranial vault distraction osteogenesis.

Polyanionic collagen membranes for guided tissue regeneration: Effect of progressive glutaraldehyde cross-linking on biocompatibility and degradation

The ultimate goal of periodontal therapy is to control periodontal tissue inflammation and to produce predictable regeneration of that part of the periodontium which has been lost as a result of periodontal disease. In guided tissue regeneration membranes function as mechanical barriers, excluding the epithelium and gingival corium from the root surface and allowing regeneration by periodontal ligament cells. This report aims to study the effect of glutaraldehyde (GA) cross-linking on mineralized polyanionic collagen (PAC) membranes by conducting a histological evaluation of the tissue response (biocompatibility) and by assessing the biodegradation of subcutaneous membrane implants in rats. We studied six different samples: a PAC, a PAC mineralized by alternate soaking processes for either 25 or 75 cycles (PAC 25 and PAC 75, respectively) and these films cross-linked by GA. Inflammatory infiltrate, cytokine dosage, fibrosis capsule thickness, metalloproteinase immunohistochemistry and membrane biodegradation after 1, 7, 15 and 30 days were measured. The inflammatory response was found to be more intense in membranes without cross-linking, while the fibrosis capsules became thicker in cross-linked membranes after 30 days. The membranes without cross-linking suffered intense biodegradation, while the membranes with cross-linking remained intact after 30 days. The cross-linking with GA reduced the inflammatory response and prevented degradation of the membranes over the entire course of the observation period. These membranes are thus an attractive option when the production of new bone depends on the prolonged presence of a mechanical barrier.

The current state of limb salvage surgery

The treatment of malignant tumors of the extremities has a long and sometimes distressing history. Resective surgery was clearly the goal of the tumor treatment teams, but the systems for reconstruction were so limited that the patients were sometimes severely disabled after wide resective surgery and amputation seemed to be the logical solution. In addition, the major difficulty encountered with treatment of tumors such as osteosarcoma, chondrosarcoma, Ewing’s tumor, and some soft tissue malignant lesions was the possibility of a local recurrence after resective surgery, which appeared to greatly increase the risk of distant metastasis. In the early days, diagnosis was made by biopsy and unless the tumor was very small or quite benign on histological study, amputation seemed to be the logical protocol. Several approaches were added in an attempt to salvage extremity function. Radiation alone was considered a possible method of therapy for some tumors, but when utilized without resective surgery often left the soft tissues and skin sufficiently damaged so as to require a later amputation. Furthermore, recurrence for radiation treated lesions was also a problem and treatment was almost always amputation. The early introduction of chemotherapy made a significant difference in the sense that it was now possible to treat the patient either after resective surgery or before and after and thus reduce the rate of local recurrence and also decrease the likelihood of metastasis. Indeed, the combination of radiation and chemotherapy and wide resective surgery greatly reduced the local recurrence rate and improved survival. It seemed apparent then that some forms of reconstruction of bony parts could make amputations much less frequent and greatly improve the patient’s functions. The reconstructive systems that were devised included metallic devices, autograft implants, and allograft transplants. Clearly, the most biologically acceptable of the three systems is autograft implantation. Osteogenetic bone substitutes have the ability to grow bone and to stimulate bone formation in the host tissues. The major type of such treatment is a fresh autograft from the iliac crest or from a rib or from the fibula or adjacent bone in the forearm or leg. If the tissue is transferred rapidly, the osteoblasts and osteocytes survive and can then begin to make new bone. Fibular grafts are easily inserted and survive and can rapidly replace the resected bone. In addition, the osteoadherin, hyaluronan, osteonectin, and bone sialoprotein present in the graft can influence the production and function of the osteoblasts to make new bone. One of the more common recent uses of such a technique is the implantation of a vascularized fibular component, which can not only add living bone, but can also bring in a vascular system that can aid the production of new bone at the site of prior injury or damage. The problems with fibular or iliac wing or rib grafts is that they are limited in size and shape and they also leave the patient with another site of disability in addition to the area of tumor resective surgery.. The second system is allografting, which has a long history. The National Naval Tissue Bank was established shortly after World War II and introduced the use of bone segments for treatment of local resective sites. Freezing the grafts reduced the host immune reactivity and allowed the inserted segment to remain intact and with limited local or systemic reactivity. The problem with the system was clearly that the bone grafts do not appear to be revascularized or heal rapidly at the host–donor junction sites. Furthermore, because they are not vascularized or develop a cellular system, they become “loci resistentia minoris” and are subject to non-union, fracture, joint arthritis and most problematical, infections. Although the grafts are now readily available from centers that have developed systems to reduce donor-transmitted infections, the rates of complications have discouraged many surgical teams. The use of some forms of bone morphogenetic proteins seems to help by causing an increased rate of synthesis of new osteoblasts or by activating existing osteoblasts.. Materials now available that are based on the presence of BMPs include Skeletal Radiol (2009) 38:733–734 DOI 10.1007/s00256-009-0728-4

Distraction osteogenesis in the adult mandible

Distraction osteogenesis is a process of slow application of force to a bone cut thereby widening the gap and resulting in production of new bone as well as soft tissue. The process has taken the maxillofacial surgeons by storm for the correction of dentofacial and craniofacial growth deficiencies. It is gaining worldwide popularity as a mode of reconstruction for numerous congenital and acquired craniomaxillofacial anomalies. Distraction osteogenesis is an excellent technique in the hands of trained oral and maxillofacial surgeons to grow the mandible not only for aesthetic purposes but to obtain an improved function in terms of mastication and airway enhancement. The paper deals with distraction of mandible obtained in young adults as a treatment modality for hemifacial microsomia, sleep apnea, micrognathia and post-ankylotic mandible. In all cases intra-oral distractors using multifocal vector were applied under local anesthesia to obtain a callous between 7 and 17 mm. The various intricacies of the procedure and results obtained are discussed. Simultaneously, the role of genioplasty is also debated in this paper.

The properties of biomimetically processed calcium phosphate on bioactive ceramics and their response on bone cells

This study looks for grounds to alter the chemical composition (phosphate, calcium, silica and carbonate), dissolution properties, structure and nanotopography of the biomimetically processed surfaces on bioactive ceramics to optimize their shown ability to influence bone cell behaviour and production of new bone. In the bone environment desirable characteristic of these materials is their ability to be remodeled by natural osteoclastic resorption. Different silica and carbonate containing calcium phosphate layers were prepared on bioactive glasses 9 (S53P4) and 1-98 (S53P2) and sol-gel processed pure silica SiO2 in C- and R-SBF (conventional and revised simulated body fluid) for varying periods of time. It was shown that in R-SBF the CaP layer formed faster compared to C-SBF. The CaP layer in the R-SBF contained more carbonate (CO3(2-)) compared to that formed with the same immersion time in C-SBF. The CaP so formed in R-SBF with faster precipitation is more amorphous than the bonelike HCA formed in C-SBF. The results indicate that the most suitable surface for both osteoblasts and osteoclasts was found to be an amorphous CaP having mesoporous nanotopography and proper dissolution rate of calcium and silica.

Direct Transformation from Quiescence to Bone Formation in the Adult Periosteum Following a Single Brief Period of Bone Loading

Abstract The concept of resorption preceding formation in a coupled response is well established as the normal sequence of remodeling in adult bone. So prevalent is this concept, however, that the idea of the direct activation of osteogenic modeling in normal adult bone is often ignored. This experiment documents the direct transformation of the normal, quiescent, adult periosteum to active bone formation. The osteogenic stimulus was provided by a single short period of dynamic loading. Periosteal activation and the production of new bone within 5 days of loading was unaccompanied by resorption or the presence of osteoclasts. We therefore conclude that an adult resting periosteum can become directly converted to formation as a physiologic response to an appropriate osteogenic stimulus without the need for resorption. To distinguish this process from remodeling we suggest it be called renewed modeling. It is notable that a single short exposure to an “osteogenic” loading regime can influence the full cascade of cellular events between quiescence and active bone formation.

Effect of gamma irradiation on the osteoinductivity of morphogenetic protein extract from reindeer bone

Background Bone morphogenetic proteins (BMPs), which are capable of stimulating the production of new bone, must be sterilized before preclinical and clinical use to reduce the risk of infections and associated complications. In this study, we investigated the effects of gamma sterilization on the osteoinductivity of native reindeer BMP extract in the Balb/C mouse thigh muscle pouch model.Methods 5 mg of native reindeer BMP extract and 5 mg of bovine serum albumin were administered separately either in gelatine capsules or mixed with gelatine as injections. The dose of gamma irradiation was 4.1 MRad. Unsterile capsules and injections served as controls. New bone formation was evaluated based on the incorporation of Ca45and also radiographically 3 weeks after implantation.Results Albumin-containing implants and injections did not induce new bone formation, as monitored in radiographs. Gamma sterilization did not reduce the osteoinductivity of native BMP extract in capsules, but a significant decrease in osteoinductivity-measured as area (50%) and Ca45incorporation of new bone (27%)-was seen after injection. Gamma sterilization had no effect on the optical density of new bone induced by native BMP extract administered in capsules or by injection.Interpretation We conclude that, as gamma irradiation did not reduce the osteoinductivity of reindeer BMP extract in gelatine capsules, this method appears to be suitable for sterilization of BMPs to be given in capsule form. Native reindeer BMP extract was more sensitive to irradiation in soluble collagen (gelatine) than BMP in gelatine capsules. This finding must be given serious consideration regarding treatment of patients, but the remaining activity may be sufficient for the induction of bone formation in preclinical and clinical situations.

A new approach to enhancement of bone formation by electrically polarized hydroxyapatite.

An electrical field may affect osteogenesis. Since we found that hydroxyapatite (HA) ceramics may be polarizable, we hypothesized that electrically polarized HA may foster production of new bone in vivo. Both polarized and non-polarized HA ceramics were inserted into the subperiosteum spaces at the parietal bone area of rats. After 2, 4, and 8 weeks, the implant sites were examined histologically. Morphometric analysis revealed that new bone formation was accelerated on the negatively charged surface of the polarized HA (N-surface) at 2 weeks. The newly formed bone approached maturation at 4 weeks and was thicker on the N-surface than in the controls. By 8 weeks, newly formed bone in the controls was almost the same as that on the N-surface. These findings suggest that polarized HA is biocompatible and that bone formation on the N-surface is enhanced in the early stage of bone healing.

In Vitro andIn Vivo induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene.

It has been well established that bone morphogenetic protein-2 (BMP-2) can induce bone formation bothin vivo andin vitro, although high concentrations (up to milligrams) of BMP-2 have been required to achieve this effectin vivo. Further, clinical applications are usually limited to a single dose at the time of implantation. In an attempt to prolong the transforming effect of BMP-2 we used a recombinant adenoviral vector carrying the human BMP-2 gene (Adv-BMP2) to transduce marrow-derived mesenchymal stem cells (MSC) of skeletally mature male New Zealand white rabbits. The pluripotential MSC were incubated with Adv-BMP2 overnight followed by culture in growth medium for 1 week. Assays on tissue cultures demonstrated that these Adv-BMP2 transduced MSC produced BMP-2 protein, differentiated into an osteoprogenitor line, and induced bone formationin vitro. These MSC had increased alkaline phosphatase activity, increased expression of type I collagen, osteopontin, and osteocalcin mRNA, and induced matrix mineralization compared with both nontransduced cells and cells transduced with a control adenoviral construct. To analyze the osteogenic potentialin vivo, Adv-BMP2-transduced MSC were autologously implanted into the intertransverse process space between L5 and L6 of the donor rabbits. The production of new bone was demonstrated by radiographic examination 4 weeks later in areas implanted with cells transduced with Adv-BMP2, whereas no bone was evident at sites implanted with cells transduced with the control adenoviral construct. Histological examination further confirmed the presence of new bone formation. These accumulated data indicate that it is possible to successfully transduce mesenchymal stem cells with a recombinant adenoviral vector carrying the gene for BMP-2 such that these cells will produce BMP-2, differentiate into an osteoprogenitor line, and induce bone formation bothin vitro andin vivo. Moreover, incubation of the Adv-BMP2-transduced cells for an additional 7 days in culture before transplantation enhances the success rate in bone formation (three out of three) as compared with our previous report (one out of five, Calcif Tissue Int 63:357-360, 1998).