Rapid and reliable healing of critical size bone defects with genetically modified sheep muscle.

Large segmental defects in bone fail to heal and remain a clinical problem. Muscle is highly osteogenic, and preliminary data suggest that autologous muscle tissue expressing bone morphogenetic protein-2 (BMP-2) efficiently heals critical size defects in rats. Translation into possible human clinical trials requires, inter alia, demonstration of efficacy in a large animal, such as the sheep. Scale-up is fraught with numerous biological, anatomical, mechanical and structural variables, which cannot be addressed systematically because of cost and other practical issues. For this reason, we developed a translational model enabling us to isolate the biological question of whether sheep muscle, transduced with adenovirus expressing BMP-2, could heal critical size defects in vivo. Initial experiments in athymic rats noted strong healing in only about one-third of animals because of unexpected immune responses to sheep antigens. For this reason, subsequent experiments were performed with Fischer rats under transient immunosuppression. Such experiments confirmed remarkably rapid and reliable healing of the defects in all rats, with bridging by 2 weeks and remodelling as early as 3-4 weeks, despite BMP-2 production only in nanogram quantities and persisting for only 1-3 weeks. By 8 weeks the healed defects contained well-organised new bone with advanced neo-cortication and abundant marrow. Bone mineral content and mechanical strength were close to normal values. These data demonstrate the utility of this model when adapting this technology for bone healing in sheep, as a prelude to human clinical trials.

Equine model for soft-tissue regeneration.

Soft-tissue regeneration methods currently yield suboptimal clinical outcomes due to loss of tissue volume and a lack of functional tissue regeneration. Grafted tissues and natural biomaterials often degrade or resorb too quickly, while most synthetic materials do not degrade. In previous research we demonstrated that soft-tissue regeneration can be supported using silk porous biomaterials for at least 18 months in vivo in a rodent model. In the present study, we scaled the system to a survival study using a large animal model and demonstrated the feasibility of these biomaterials for soft-tissue regeneration in adult horses. Both slow and rapidly degrading silk matrices were evaluated in subcutaneous pocket and intramuscular defect depots. We showed that we can effectively employ an equine model over 6 months to simultaneously evaluate many different implants, reducing the number of animals needed. Furthermore, we were able to tailor matrix degradation by varying the initial format of the implanted silk. Finally, we demonstrate ultrasound imaging of implants to be an effective means for tracking tissue regeneration and implant degradation.

Use of genetically modified muscle and fat grafts to repair defects in bone and cartilage.

We report a novel technology for the rapid healing of large osseous and chondral defects, based upon the genetic modification of autologous skeletal muscle and fat grafts. These tissues were selected because they not only possess mesenchymal progenitor cells and scaffolding properties, but also can be biopsied, genetically modified and returned to the patient in a single operative session. First generation adenovirus vector carrying cDNA encoding human bone morphogenetic protein-2 (Ad.BMP-2) was used for gene transfer to biopsies of muscle and fat. To assess bone healing, the genetically modified ("gene activated") tissues were implanted into 5mm-long critical size, mid-diaphyseal, stabilized defects in the femora of Fischer rats. Unlike control defects, those receiving gene-activated muscle underwent rapid healing, with evidence of radiologic bridging as early as 10 days after implantation and restoration of full mechanical strength by 8 weeks. Histologic analysis suggests that the grafts rapidly differentiated into cartilage, followed by efficient endochondral ossification. Fluorescence in situ hybridization detection of Y-chromosomes following the transfer of male donor muscle into female rats demonstrated that at least some of the osteoblasts of the healed bone were derived from donor muscle. Gene activated fat also healed critical sized defects, but less quickly than muscle and with more variability. Anti-adenovirus antibodies were not detected. Pilot studies in a rabbit osteochondral defect model demonstrated the promise of this technology for healing cartilage defects. Further development of these methods should provide ways to heal bone and cartilage more expeditiously, and at lower cost, than is presently possible.

BMP-silk composite matrices heal critically sized femoral defects.

Clinical drawbacks of bone grafting prompt the search for alternative bone augmentation technologies such as use of growth and differentiation factors, gene therapy, and cell therapy. Osteopromotive matrices are frequently employed for the local delivery and controlled release of these augmentation agents. Some matrices also provide an osteoconductive scaffold to support new bone growth. In this study, silkworm-derived silk fibroin was evaluated as an osteoconductive matrix for healing critical sized mid-femoral segmental defects in nude rats. Four treatment groups were assessed over eight weeks: silk scaffolds (SS) with recombinant human BMP-2 (rhBMP-2) and human mesenchymal stem cells (HMSC) that had been pre-differentiated along an osteoblastic lineage ex vivo (Group I; pdHMSC/rhBMP-2/SS); SS with rhBMP-2 and undifferentiated HMSCs (Group II; udHMSC/rhBMP-2/SS); SS and rhBMP-2 alone (Group III; rhBMP-2/SS); and empty defects (Group IV). Bi-weekly radiographs revealed a progressive and similar increase in Group I-III mean defect mineralization through post-operative week (POW) 8. Radiographs, dual energy x-ray absorptiometry, and micro-computed tomography confirmed that Groups I-III exhibited similar substantial and significantly (p<0.05) greater defect mineralization at POW 8 than the unfilled Group IV defects which remained void of bone. No significant differences in Groups I-III defect healing at POW 8 were apparent using these same assays or mechanical testing. Histology at POW 8 revealed moderately good bridging of the parent diaphyseal cortices with woven and lamellar bone bridging islands of silk matrix in Groups I and III. Group II defects possessed comparatively less new bone which was most abundant adjacent to the parent bone margins. Elsewhere the silk matrix was more often enveloped by poorly differentiated loose fibrous connective tissue. Group IV defects showed minimal new bone formation. None of the treatment groups attained the mean mineralization or the mean biomechanical strength of identical defects implanted with SS and pdHMSCs alone in a previous study. However, addition of rhBMP-2 to SS prompted more bone than was previously generated using udHMSC/SS or SS alone. These data imply the clinical potential of silk scaffolds and rhBMP-2 as composite osteopromotive implants when used alone or with select stem cell populations. Additional studies in larger species are now warranted.

Silk based biomaterials to heal critical sized femur defects.

Bone auto- and allografts have inherent drawbacks, therefore the treatment of non-unions and critical size defects in load bearing long bones would benefit from the use of osteopromotive biodegradable, biocompatible and mechanically durable matrices to enhance migration or delivery of cell populations and/or morphogens/cytokines. Silk fibroin biomaterial scaffolds were evaluated as osteopromotive matrices in critical sized mid-femoral segmental defects in nude rats. Four treatment groups were assessed over 8 weeks in vivo: silk scaffolds (SS) with human mesenchymal stem cells (hMSCs) that had previously been differentiated along an osteoblastic lineage in vitro (group I; pdHMSC/SS); SS with undifferentiated hMSCs (group II; udHMSC/SS); SS alone (group III; SS); and empty defects (group IV). When hMSCs were cultured in vitro in osteogenic medium for 5 weeks, bone formation was characterized with bimodal peak activities for alkaline phosphatase at 2 and 4 weeks. Calcium deposition started after 1 week and progressively increased to peak at 4 weeks, reaching cumulative levels of deposited calcium at 16 mug per mg scaffold wet weight. In vivo osteogenesis was characterized by almost bridged defects with newly formed bone after 8 weeks in group I. Significantly (P < 0.01) greater bone volumes were observed with the pdHMSC/SS (group I) implants than with groups II, III or IV. These three groups failed to induce substantial new bone formation and resulted in the ingrowth of cells with fibroblast-like morphology into the defect zone. The implantation of pdHMSC/SS resulted in significantly (P < 0.05) greater maximal load and torque when compared to the other treatment regimens. The pdHMSC/SS implants demonstrated osteogenic ability in vitro and capacity to thrive towards the healing of critical size femoral segmental defects in vivo. Thus, these new constructs provide an alternative protein-based biomaterial for load bearing applications.

Surgical repair of rib fractures in 14 neonatal foals: case selection, surgical technique and results.

REASONS FOR PERFORMING STUDY: Fractured ribs are encountered quite frequently in newborn Thoroughbred foals, often with fatal outcome. Surgical repair of fractures therefore requires consideration as a means of reducing mortality. OBJECTIVES: To evaluate the repair of rib fractures using internal fixation techniques in foals at 2 different equine hospitals following similar diagnostics and case selection. METHODS: The records of 14 foals that underwent internal fixation of fracture ribs were reviewed. Subject details, clinical presentation, diagnosis, surgical technique, post operative care and complications were recorded. Follow-up information was obtained in 7 foals. RESULTS: The fractured ribs were reduced and stabilised using reconstruction plate(s), self-tapping cortical screws and cerclage wire in 12 cases, Steinmann pins and cerclage wires in 1 case and both techniques in 1 case. Not every rib was reduced on each case. Surgical reduction was performed on an average of 2 ribs, range 1-3 ribs in each foal. At the time of writing, 4 foals had been sold, one age 2 years was in training and 2 others died from unrelated causes. CONCLUSIONS: Our data support the use of surgical stabilisation utilising reconstruction plates, self-tapping cortical screws and cerclage wire for selected cases of thoracic trauma in neonatal foals. The use of Steinmann pins may be suboptimal due to cyclic failure, implant migration and the potential for iatrogenic internal thoracic trauma. POTENTIAL RELEVANCE: Foals with existing extensive internal thoracic trauma resulting from rib fracture(s), or the potential for such trauma, previously considered to have a guarded to poor prognosis for survival, may be successfully managed with internal fixation of selected fracture sites.

Intravenous lidocaine and small-intestinal size, abdominal fluid, and outcome after colic surgery in horses.

Twenty-eight horses with the diagnosis of an intestinal disorder requiring surgical intervention were randomly assigned to lidocaine (n = 13) or saline (control, n = 15) treatment groups. After induction of anesthesia, treated horses received a loading dose of 2% lidocaine (0.65 mg/kg) intravenously, followed by a continuous rate of infusion of 1% lidocaine (0.025 mg/kg/min) until the discontinuation of anesthesia. Upon recovery from anesthesia, a 2nd loading dose of 2% lidocaine (1.3 mg/kg) was administered, followed by an infusion of 1% lidocaine (0.05 mg/kg/min) for 24 hours postoperatively. The control group received equivalent volumes of saline. Lidocaine-treated horses had significantly better minimum jejunal cross-sectional area scores (P = .011), minimum jejunal diameter scores (P = .002), and intestinal ultrasound index (IUI) (P = .007). Peritoneal fluid was detected by percutaneous ultrasound examination in 8 of the 15 control animals but in none of the treated animals (P = .003). Failure to obtain fluid via abdominocentesis was significantly more frequent for lidocaine-treated horses (P = .025). No significant differences between the groups were found in the presence of gastrointestinal sounds, time to passage of 1st feces, number of defecations in the 1st 24 hours, presence of gastric reflux, duodenal or jejunal wall thickness, maximum duodenal or jejunal diameter or cross-sectional area, minimum duodenal diameter or cross-sectional area, duodenal and jejunal intraluminal echogenicity, small-intestinal contractions per minute, rate of complications, or outcome. On the basis of this study, lidocaine infusion may have some desirable effects on jejunal distension and peritoneal fluid accumulation and was well tolerated perioperatively in horses with colic. The low incidence of small-intestinal lesions and gastric reflux in the study makes it difficult to assess the use of lidocaine in the prevention of postoperative ileus (POI).

Comparison of two methods for presurgical disinfection of the equine hoof.

OBJECTIVES: To determine for equine hooves the normal resident aerobic bacterial population and the efficacy of 2 methods of disinfection. Study Design-Measurement of total bacterial, gram-positive bacterial, and gram-negative bacterial surface populations from the frog, sole, and hoof wall after each step of 2 different preoperative surgical disinfection techniques. ANIMALS: Six adult horses. METHODS: Hoof wall, sole, and frog samples were collected for quantitative bacteriology before, during, and after 2 multistep antiseptic preparation techniques: Method A-6-minute scrub with povidone-iodine soap, followed by 24-hour submersion in povidone-iodine solution-soaked cotton; and Method B-initial removal of superficial layer of hoof capsule before completing Method A disinfection procedures. RESULTS: Removal of the superficial hoof layer, application of the povidone iodine scrub, and completion of the povidone-iodine soak all significantly (P < .0008) decreased total bacterial numbers. Method B had significantly lower bacterial counts than method A at each consecutive step. Final total bacterial counts remained greater than 10(5) bacteria per gram of tissue regardless of preparation method. CONCLUSIONS: The hoof surface hosts a broad spectrum of aerobic gram-positive and -negative bacteria, many of which are potential pathogens. Bacterial numbers can be significantly reduced by removal of the superficial hoof surface, by application of a povidone-iodine scrub, and by use of a 24-hour povidone-iodine soak. However, bacterial populations >10(5) g per tissue persist after these disinfection procedures. CLINICAL RELEVANCE: Regardless of the preparation methods used in this study, bacterial populations capable of inducing wound infection remain on the hoof capsule.

Safety of an oral chondroprotective agent in horses.

Six healthy, adult female horses were administered five times the minimum maintenance dose of an oral low-molecular-weight chondroitin sulfate, glucosamine HCl, and manganese ascorbate chondroprotective agent (Cosequin; Nutramax Laboratories, Inc., Edgewood, MD) daily for 35 days. Hematology, serum biochemistry, and synovial fluid parameters were assessed twice prior to administering the product and again at the end of the treatment period. Physical examinations performed daily throughout the study showed no abnormal clinical changes attributable to the product. All hematologic parameters measured were within normal reference ranges; however, hematocrit, hemoglobin, and white blood cell counts were significantly (P < .05) increased after treatment, as compared with values on Day 0. Mean serum urea nitrogen was mildly elevated above the reference range before and after treatments, and mean serum creatinine was significantly (P < .05) decreased after treatment. Several other biochemical parameters (calcium, phosphorus, potassium, total and indirect bilirubin, alkaline phosphatase, gamma-glutamyltransferase, lactic dehydrogenase, and sodium:potassium ratio) were significantly (P < .05) altered following administration of the chondroprotectant, but all remained within normal reference ranges. Mean creatine kinase levels were significantly higher after treatment than on Day 0 (429 U/L versus 310 U/L), but this represented only a mild elevation relative to the reference range (10 to 350 U/L). Synovial fluid total protein and specific gravity were unaffected. The minor shifts encountered in hematology and serum biochemistry parameters are not considered to have clinical significance. The results of this study suggest that the oral chondroprotective agent tested is safe for administration to horses at recommended dose rates.

Potential applications and delivery strategies for bone morphogenetic proteins.

Bone morphogenetic proteins (BMPs) are multifunctional cytokines which are members of the Transforming Growth Factor-beta superfamily. They are the only signaling molecules which can singly induce de novo bone formation at orthotopic and heterotopic sites and their osteoinductive potency makes them clinically valuable as alternatives to bone graft. Several means of delivering BMPs to patients are undergoing evaluation including systemic administration, gene transfer and local matrix delivery vehicle implantation. The latter methodology is in advanced stages of development for application in humans in the treatment of selected spinal fusions, fracture repairs, craniomaxillofacial surgery and periodontal injury and disease. The BMPs are also widely distributed in non-skeletal tissues such as nerve, gastrointestinal tract, kidney, heart and lungs and they have a central role in vertebrate and non-vertebrate organogenesis. Initial studies indicate that the BMPs have neuro, cardio and reno-protective actions and it is likely that therapeutic indications for their use will extend well beyond skeletal disease and injury.

Concentrations of substance P and prostaglandin E2 in synovial fluid of normal and abnormal joints of horses.

OBJECTIVE: To correlate substance P content of synovial fluid with prostaglandin E2 content, radiographic evidence of joint abnormality, and anatomic location of the joint for normal and osteoarthritic joints of horses. SAMPLE POPULATION: Synovial fluid from 46 normal joints in 21 horses and 16 osteoarthritic joints in 10 horses. PROCEDURE: Normal and osteoarthritic joints were identified by clinical and radiographic examination, by response to nerve blocks, during scintigraphy or surgery, or by clinicopathologic evaluation. Substance P and prostaglandin E2 contents of synovial fluid were determined by radioimmunoassay. Radio-graphs of joints were assigned a numeric score reflecting severity of lesions. Joints were assigned a numeric score reflecting anatomic location. RESULTS: Median concentrations of substance P and prostaglandin E2 were significantly increased in osteoarthritic joints, compared with normal joints. A significant correlation was found between concentrations of substance P and prostaglandin E2 in synovial fluid, but a correlation was not detected between substance P concentration in synovial fluid and anatomic location of the joint or between radiographic scores of osteoarthritic joints and concentrations of substance P or prostaglandin E2. CONCLUSIONS AND CLINICAL RELEVANCE: A correlation existed between concentrations of substance P and prostaglandin E2 in synovial fluid obtained from normal and osteoarthritic joints. However, content of substance P in synovial fluid cannot be predicted by the radiographic appearance of the joint or its anatomic location. Substance P and prostaglandin E2 may share an important and related role in the etiopathogenesis of osteoarthritis, lending credence to the importance of neurogenic inflammation in horses.

Critically sized osteo-periosteal femoral defects: a dog model.

A 21-mm defect was created in 1 femoral diaphysis each of 15 dogs. Periosteum as well as a cylinder of bone was removed, and the defect was stabilized with a bone plate. Twelve of the defects were filled with an equal volume of autogenous cancellous bone harvested from the ipsilateral ilium. Three defects were left untreated. Cranial to caudal radiographs were taken postoperatively and every 4 weeks for 16 weeks. The radiographs were evaluated for healing using two ordinal scales. At 16 weeks, the dogs were euthanized and the femurs harvested for biomechanical testing and histologic evaluation. Both operated and contralateral not operated femurs were mechanically tested to failure in torsion, and load at failure and stiffness were calculated. All dogs tolerated the procedure well, and were using the operated limb within 1 or 2 days postoperatively. There were no complications noted during the 16 weeks of the study. Unfilled defects did not heal and became atrophic nonunions. The defects filled with autogenous cancellous bone healed in a consistent pattern of consolidation, incorporation, and remodeling, with uniform increases of both ordinal scales used. The femoral cortex opposite the bone plate demonstrated most mature remodeling, evident both radiographically as well as histologically. Unoperated femurs failed at 13.61 +/- 3.88 N-m and grafted femurs failed at 2.96 +/- 1.3 N-m, which was 23% of the measurement of the unoperated femur. Relative stiffness of the unoperated femurs was 5974 +/- 4316 N-m2/radian, and grafted femurs had a relative stiffness of 642 +/- 561 N-m2/radian, which was 10.4% of the measurement of unoperated femur. This model proved to be a critically sized defect, which when left unfilled resulted in an atrophic nonunion, and when filled with cancellous bone resulted in a consistent healing pattern.

A comparison of the Synthes 4.5-mm cannulated screw and the Synthes 4.5-mm standard cortex screw systems in equine bone.

OBJECTIVE: To determine risk of failure of the Synthes 4.5-mm cannulated screw system instrumentation in equine bone and to compare its application with the Synthes 4.5-mm standard cortex screw system. STUDY DESIGN: The maximum insertion torque of the cannulated and standard cortex screw systems were compared with the ultimate torsional strengths of the equipment. Pullout strength and ultimate tensile load of cannulated and standard cortex screws were also determined. SAMPLE POPULATION: Paired equine cadaver third metacarpal and third carpal bones. METHODS: Maximum insertion torque and ultimate torsional strengths were determined by using an axial-torsional, servohydraulic materials testing system and a hand-held torquometer. Pullout tests were performed by using a servohydraulic materials testing system. RESULTS: Maximum insertion torque of all cannulated instrumentation was less than ultimate torsional strength at all locations (P < .05). Maximum insertion torques of cannulated taps and screws were greater than for standard taps and screws in the third carpal bone (P < .002). Pullout strength of the cannulated screws was less than the standard cortex screws at all sites (P < .001). Cannulated screws broke before bone failure in all but one bone specimen. CONCLUSIONS: The risk of cannulated instrument or screw failure during insertion into bone is theoretically low. The relatively low pullout strength of the cannulated screws implies that the interfragmentary compression achievable is likely to be less than with standard cortex screws. CLINICAL RELEVANCE: The relatively low pullout strength of the cannulated screw suggests that its risk of failure during fracture repair is greater than with the standard cortex screw.

Healing bone using recombinant human bone morphogenetic protein 2 and copolymer.

Middiaphyseal 2.5-cm segmental defects in the right femurs of 12 sheep were stabilized with stainless steel plates and implanted with (1) 2 mg recombinant human bone morphogenetic protein 2 and poly[D,L-(lactide-co-glycolide)] bioerodible polymer with autologous blood (n = 7), (2) 4 mg recombinant human bone morphogenetic protein 2 and poly[D,L-(lactide-co-glycolide)] and blood (n = 3), or (3) poly[D,L-(lactide-co-glycolide)] and blood only (n = 2). Bone healing was evaluated for 1 year using clinical, radiographic, gross pathologic, and histologic techniques. Union occurred in three sheep in Group 1, two in Group 2, and none in Group 3. In the animals that healed, new bone first was visible radiographically between Weeks 2 and 6 after implantation; new bone mineral content equaled that of the intact femur not surgically treated by Week 16; recanalization of the medullary cavity approached completion at Week 52; and at necropsy the surgical treated femurs were rigidly healed, the poly[D,L-(lactide-co-glycolide)] was resorbed completely, and woven and lamellar bone bridged the defect site. In two Group 1 sheep euthanized at Weeks 2 and 6, polymer particles were permeated by occasional multinucleated giant cells. Some plasma cells, lymphocytes, and neutrophils were present locally. The poly[D,L-(lactide-co-glycolide)] tended to fragment during surgical implantation. Despite these observations, the recombinant human bone morphogenetic protein 2/poly[D,L-(lactide-co-glycolide)] implant was able to heal large segmental bone defects in this demanding model.

A new animal model for maxillary sinus floor augmentation: evaluation parameters.

This study describes a novel animal model of the maxillary sinus floor augmentation procedure used to assess bone formation during 12 weeks in response to a recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) sinus implant. A buffer-ACS implant was used as a control. Animal response was monitored using computerized tomography and physical, hematologic, gross pathologic, and histologic evaluations. The rhBMP-2/ACS implants maintained a relatively constant size postsurgery and showed a time-dependent increase in mineralization. The buffer/ACS control implants failed to mineralize and were resorbed by 4 weeks. The model served effectively and without complication. Results indicate rhBMP-2/ACS implants deserve consideration as alternatives to traditional grafting procedures.

Endodontic therapy and surgical excision of a chronic suppurative osteomyelitic lesion in a horse: a case report.

A 22-year-old thoroughbred gelding was presented for evaluation and treatment of chronic dental disease. The horse had a history of quidding and abnormal bite behavior. Intraoral examination revealed signs of chronic generalized gingival inflammation and severe dental caries affecting the maxillary and mandibular incisor teeth. Treatment was provided on two separate visits over an interval of four months. The first visit consisted of the surgical extraction of three unrestorable incisor teeth and restoration of six carious maxillary incisor teeth. The second visit consisted of conventional endodontic therapy on the remaining mandibular incisor teeth and the surgical removal of a chronic suppurative osteomyelitic lesion. Immediate and long term improvements in eating habits were noted. Three month follow-up examinations following completion of treatment have shown the teeth to be in functional position, the restorations intact, and the surgical site well healed.

The role of computed tomography in evaluation of subchondral osseous lesions in seven horses with chronic synovitis.

Seven horses with severe, persistent lameness of sudden onset were evaluated with scintigraphy and/or computed tomography. The lameness was localised to the front fetlock joint in 2 horses and to the tibiotarsal joint in 5 horses. Five of the horses had a history of intra-articular injections of the involved joint prior to presentation. All horses had effusion of the affected joint and were positive to flexion tests. Intraarticular anaesthesia eliminated or improved the lameness in 4 cases and a nerve conduction block proximal to the affected joint improved the lameness in another. Cytology examination of fluid from affected joints identified normal joint fluid (one horse) or elevations in nucleated cell counts of 0.9 x 10(9)/l-36.8 x 10(9)/l and total protein 20-42 g/l (6 horses). The joint fluid of 2 of these horses cultured positive for bacteria. Initial radiographs were either normal (4 cases) or the changes seen were not sufficient to explain the degree of lameness. In the 6 cases where scintigraphy was performed, intense focal isotope uptake was found in the suspected region, which corresponded to the proximal portion of the first phalanx (2 cases), distal tibia (2 cases), or talus (3 cases). Computed tomography (CT) was performed because occult fracture or osteomyelitis was suspected; and knowledge of the precise anatomical location of the lesion was considered necessary to assess the need for surgery and to plan the surgical approach. Hypodense focal lesions with hyperdense haloes were found in the subchondral bone deep to the sagittal groove of the first phalanx (P1) (2 cases) in the cochlea of the distal tibia (2 cases), and in the intertrochlear portion of the talus (3 cases). Communication between the lesion and the joint space was demonstrated by CT in 5 cases. Post mortem examination of one case revealed synovitis and a chronic bone abscess (Brodie's abscess) communicating with the joint space.

Bone formation in the goat maxillary sinus induced by absorbable collagen sponge implants impregnated with recombinant human bone morphogenetic protein-2.

This study assessed the efficacy, safety, and technical feasibility of inducing bone formation in an animal model of maxillary sinus floor augmentation using recombinant human bone morphogenetic protein-2 (rhBMP-2) impregnated on an absorbable collagen sponge (ACS). Bilateral antral maxillary sinus floor elevation procedures were surgically performed in six adult female Alpine-Saanen goats. Bone formation in response to the implant was evaluated using sequential radiographs, computerized tomography, and gross pathologic and histologic analysis performed at necropsy. Computerized tomographic scans documented nonosseous radiopacity in both sinuses postimplantation. Sinuses implanted with the rhBMP-2/ACS subsequently demonstrated increasing radiopacity local to the implant site, while radiopacity of the negative control sinuses remained unchanged or decreased. The results demonstrated the ability of an rhBMP-2/ACS implant to induce substantive new bone formation within the maxillary sinus of goats without adverse sequelae. The rhBMP-2/ACS composite implant may represent an acceptable alternative to traditional bone grafts and bone substitutes for maxillary sinus floor augmentation procedures in humans.