Histomorphometric evaluation of bone healing in rabbit fibular osteotomy model without fixation

<p>Abstract</p> <p>Background</p> <p>Animal models of fracture consolidation are fundamental for the understanding of the biological process of bone repair in humans, but histological studies are rare and provide only qualitative results. The objective of this article is to present the histomorphometric study of the bone healing process using an experimental model of osteotomy in rabbit fibula without interference of synthesis material.</p> <p>Methods</p> <p>Fifteen rabbits were submitted to fibular osteotomy without any fixation device. Groups of five animals were submitted to pharmacological euthanasia during a period of one (group A), two (group B) and four weeks (group C) after osteotomy. Histomorphometric evaluation was performed in the histological sections.</p> <p>Results</p> <p>During week one there was intense cellularity (67/field), a large amount of woven bone (75.7%) and a small amount of lamellar bone (7.65%). At two weeks there was a decrease in woven bone (41.59%) and an increase in lamellar bone (15.16%). At four weeks there was a decrease of cellularity (19.17/field) and lamellar bone (55.56%) exceeded the quantity of woven bone (31.68%).</p> <p>Conclusion</p> <p>Histomorphometric (quantitative) evaluation of the present study was shown to be compatible with bone healing achieved in qualitative experimental models that have been commended in the literature.</p

The development of a novel model of direct fracture healing in the rat

OBJECTIVES: Small animal models of fracture repair primarily investigate indirect fracture healing via external callus formation. We present the first described rat model of direct fracture healing. METHODS: A rat tibial osteotomy was created and fixed with compression plating similar to that used in patients. The procedure was evaluated in 15 cadaver rats and then in vivo in ten Sprague-Dawley rats. Controls had osteotomies stabilised with a uniaxial external fixator that used the same surgical approach and relied on the same number and diameter of screw holes in bone. RESULTS: Fracture healing occurred without evidence of external callus on plain radiographs. At six weeks after fracture fixation, the mean stress at failure in a four-point bending test was 24.65 N/mm(2) (sd 6.15). Histology revealed ‘cutting-cones’ traversing the fracture site. In controls where a uniaxial external fixator was used, bone healing occurred via external callus formation. CONCLUSIONS: A simple, reproducible model of direct fracture healing in rat tibia that mimics clinical practice has been developed for use in future studies of direct fracture healing

Small Oscillatory Accelerations, Independent of Matrix Deformations, Increase Osteoblast Activity and Enhance Bone Morphology

A range of tissues have the capacity to adapt to mechanical challenges, an attribute presumed to be regulated through deformation of the cell and/or surrounding matrix. In contrast, it is shown here that extremely small oscillatory accelerations, applied as unconstrained motion and inducing negligible deformation, serve as an anabolic stimulus to osteoblasts in vivo. Habitual background loading was removed from the tibiae of 18 female adult mice by hindlimb-unloading. For 20 min/d, 5 d/wk, the left tibia of each mouse was subjected to oscillatory 0.6 g accelerations at 45 Hz while the right tibia served as control. Sham-loaded (n = 9) and normal age-matched control (n = 18) mice provided additional comparisons. Oscillatory accelerations, applied in the absence of weight bearing, resulted in 70% greater bone formation rates in the trabeculae of the metaphysis, but similar levels of bone resorption, when compared to contralateral controls. Quantity and quality of trabecular bone also improved as a result of the acceleration stimulus, as evidenced by a significantly greater bone volume fraction (17%) and connectivity density (33%), and significantly smaller trabecular spacing (−6%) and structural model index (−11%). These in vivo data indicate that mechanosensory elements of resident bone cell populations can perceive and respond to acceleratory signals, and point to an efficient means of introducing intense physical signals into a biologic system without putting the matrix at risk of overloading. In retrospect, acceleration, as opposed to direct mechanical distortion, represents a more generic and safe, and perhaps more fundamental means of transducing physical challenges to the cells and tissues of an organism

An Ultrasound Assisted Anchoring Technique (BoneWelding® Technology) for Fixation of Implants to Bone – A Histological Pilot Study in Sheep

The BoneWelding® Technology offers new opportunities to anchor implants within bone. The technology melted the surface of biodegradable polymer pins by means of ultrasound energy to mould material into the structures of the predrilled bone. Temperature changes were measured at the sites of implantation in an in vitro experiment. In the in vivo part of the study two types of implants were implanted in the limb of sheep to investigate the biocompatibility of the method. One implant type was made of PL-DL-lactide (PLA), the second one was a titanium core partially covered with PLA. Healing period was 2 and 6 months, with 3 sheep per group. Bone samples were evaluated radiologically, histologically and histomorphometrically for bone remodeling and inflammatory reactions. Results demonstrated mild and short temperature increase during insertion. New bone formed at the implant without evidence of inflammatory reaction. The amount of adjacent bone was increased compared to normal cancellous bone. It was concluded that the BoneWelding® Technology proved to be a biocompatible technology to anchor biodegradable as well as titanium-PLA implants in bone

Unanesthetized Auditory Cortex Exhibits Multiple Codes for Gaps in Cochlear Implant Pulse Trains

Cochlear implant listeners receive auditory stimulation through amplitude-modulated electric pulse trains. Auditory nerve studies in animals demonstrate qualitatively different patterns of firing elicited by low versus high pulse rates, suggesting that stimulus pulse rate might influence the transmission of temporal information through the auditory pathway. We tested in awake guinea pigs the temporal acuity of auditory cortical neurons for gaps in cochlear implant pulse trains. Consistent with results using anesthetized conditions, temporal acuity improved with increasing pulse rates. Unlike the anesthetized condition, however, cortical neurons responded in the awake state to multiple distinct features of the gap-containing pulse trains, with the dominant features varying with stimulus pulse rate. Responses to the onset of the trailing pulse train (Trail-ON) provided the most sensitive gap detection at 1,017 and 4,069 pulse-per-second (pps) rates, particularly for short (25 ms) leading pulse trains. In contrast, under conditions of 254 pps rate and long (200 ms) leading pulse trains, a sizeable fraction of units demonstrated greater temporal acuity in the form of robust responses to the offsets of the leading pulse train (Lead-OFF). Finally, TONIC responses exhibited decrements in firing rate during gaps, but were rarely the most sensitive feature. Unlike results from anesthetized conditions, temporal acuity of the most sensitive units was nearly as sharp for brief as for long leading bursts. The differences in stimulus coding across pulse rates likely originate from pulse rate-dependent variations in adaptation in the auditory nerve. Two marked differences from responses to acoustic stimulation were: first, Trail-ON responses to 4,069 pps trains encoded substantially shorter gaps than have been observed with acoustic stimuli; and second, the Lead-OFF gap coding seen for <15 ms gaps in 254 pps stimuli is not seen in responses to sounds. The current results may help to explain why moderate pulse rates around 1,000 pps are favored by many cochlear implant listeners

Biocompatibility and Bone Formation of Flexible, Cotton Wool-like PLGA/Calcium Phosphate Nanocomposites in Sheep

BACKGROUND: The purpose of this preliminary study was to assess the in vivo performance of synthetic, cotton wool-like nanocomposites consisting of a biodegradable poly(lactide-co-glycolide) fibrous matrix and containing either calcium phosphate nanoparticles (PLGA/CaP 60:40) or silver doped CaP nanoparticles (PLGA/Ag-CaP 60:40). Besides its extraordinary in vitro bioactivity the latter biomaterial (0.4 wt% total silver concentration) provides additional antimicrobial properties for treating bone defects exposed to microorganisms. MATERIALS AND METHODS: Both flexible artificial bone substitutes were implanted into totally 16 epiphyseal and metaphyseal drill hole defects of long bone in sheep and followed for 8 weeks. Histological and histomorphological analyses were conducted to evaluate the biocompatibility and bone formation applying a score system. The influence of silver on the in vivo performance was further investigated. RESULTS: Semi-quantitative evaluation of histology sections showed for both implant materials an excellent biocompatibility and bone healing with no resorption in the adjacent bone. No signs of inflammation were detectable, either macroscopically or microscopically, as was evident in 5 µm plastic sections by the minimal amount of inflammatory cells. The fibrous biomaterials enabled bone formation directly in the centre of the former defect. The area fraction of new bone formation as determined histomorphometrically after 8 weeks implantation was very similar with 20.5 ± 11.2 % and 22.5 ± 9.2 % for PLGA/CaP and PLGA/Ag-CaP, respectively. CONCLUSIONS: The cotton wool-like bone substitute material is easily applicable, biocompatible and might be beneficial in minimal invasive surgery for treating bone defects

Effect of Ibandronate on Bending Strength and Toughness on Rodent Cortical bone; possible implications for fracture prevention

OBJECTIVES: There remains conflicting evidence regarding cortical bone strength following bisphosphonate therapy. As part of a study to assess the effects of bisphosphonate treatment on the healing of rat tibial fractures, the mechanical properties and radiological density of the uninjured contralateral tibia was assessed. METHODS: Skeletally mature aged rats were used. A total of 14 rats received 1µg/kg ibandronate (iban) daily and 17 rats received 1 ml 0.9% sodium chloride (control) daily. Stress at failure and toughness of the tibial diaphysis were calculated following four-point bending tests. RESULTS: Uninjured cortical bone in the iban group had a significantly greater mean (standard deviation (sd)), p < 0.001, stress at failure of 219.2 MPa (sd 45.99) compared with the control group (169.46 MPa (sd 43.32)) following only nine weeks of therapy. Despite this, the cortical bone toughness and work to failure was similar. There was no significant difference in radiological density or physical dimensions of the cortical bone. CONCLUSIONS: Iban therapy increases the stress at failure of uninjured cortical bone. This has relevance when normalising the strength of repair in a limb when comparing it with the unfractured limb. However, the 20% increase in stress at failure with iban therapy needs to be interpreted with caution as there was no corresponding increase in toughness or work to failure. Further research is required in this area, especially with the increasing clinical burden of low-energy diaphyseal femoral fractures following prolonged use of bisphosphonates. Cite this article: Bone Joint Res 2015;4:99–10