Bone Healing In Rats Research Articles

Safety and Efficacy of Botulinum Toxin A in Children Undergoing Lower Limb Lengthening and Deformity Correction: Results of a Double-blind, Multicenter, Randomized Controlled Trial.

Lengthening of the lower limb is a complex procedure in which pain management and complications such as pin-site infections and muscle contractures impact the family and affect the child's quality of life. As a result, the paralytic and antinociceptive actions of neurotoxins may be indicated in managing these complications; however, few studies have explored ways to improve outcomes after lengthenings. The objective of this study was to evaluate the safety and efficacy of botulinum toxin A (BTX-A) in children undergoing lower limb lengthenings and deformity correction. Participants with a congenital or acquired deformity of the lower extremity requiring surgery to one limb were randomized to receiving either BTX-A as a single dose of 10 units per kilogram body weight, or an equivalent volume of saline solution. Pain, medication, quality of life, and physical function were assessed at different time-points. Adverse events were recorded in all participants. T test and χ tests were used to compare potential differences across both groups. Mean age of the 125 participants was 12.5 years (range, 5 to 21 y), and lengthenings averaged 4.2 cm. Maximum pain scores on day 1 postoperatively were lower in the BTX-A group (P=0.03) than in the placebo group, and remained significant favoring botox when stratifying by location of lengthening (femur vs. tibia). Clinical benefits for BTX-A were found for 3 quality of life domains at mid-distraction and end-distraction. When stratifying according to location of lengthening, there were significantly fewer pin-site infections in the tibia favoring botox (P=0.03). The amount of adverse events and bone healing indices were no different in both groups. The clinical differences in quality of life, the lower pain on the first postoperative day, and the lower number of pin-site infections in the tibia favoring BTX-A support its use as an adjunctive treatment to the lengthening process. The detailed analyses of pain patterns help inform families on the pain expectations during lower limb lengthenings. The amount of adverse events were no different in both groups, and bone healing rates were similar, indicating that the use of BTX-A in children undergoing limb lengthening and deformity correction is safe. Level I.

Potential application of nano-hydroxyapatite in treatment of osteoporotic bone healing - a preliminary study

Event Abstract Back to Event Potential application of nano-hydroxyapatite in treatment of osteoporotic bone healing - a preliminary study Xiao Yang1, Pengfei Xie1, Xuening Chen1, Xiangdong Zhu1, Yujiang Fan1 and Xingdong Zhang1 1 Sichuan University, National Engineering Research Center for Biomaterials, China Osteoporotic fracture is a significant cause of morbidity and mortality in elderly population. Delayed bone union or nonunion often occurred in clinical osteoporotic fracture. Natural osteoporotic bone hydroxyapatite crystal is within nano-dimension[1]. Thus, we hypothesized that material which contains hydroxyapatite nano particles (HANP) would have good biocompatibility with osteoporotic bone derived osteoblast (bone forming cell). HANP is made by traditional two-step synthesis method and later confirmed by TEM and XRD. Primary osteoblast culture is isolated from osteoporotic and healthy rat long bones. The osteoblasts are treated with different concentration of HANP, ranging from 0 to 500 ug/ml. MTT, confocal imaging, ELISA and RT-PCR were done to characterize cellular response to HANP. We found that 100 ug/ml HANP treated osteoporotic osteoblast had larger cell spread area (+48%, p=0.034) and higher bone related protein secretion (alkaline phosphatase and osteocalcin etc.). At this concentration of HANP, bone forming marker genes: bsp, ocn, alp and osx mRNA expression is significantly increased (p<0.05 vs. 0 ug/ml). These positive alterations may attribute to a higher cellular calcium ion concentration, measured by flow cytometry. Significant increase in cellular sodium-potassium ATPase level with exposure to 100 ug/ml HANP played an important role in cellular calcium intake. Animal bone defect model showed that with 100 ug/ml injection of HANP, ovariectomized rat had faster bone healing rate as compare with non-treated control. We conclude that below 500 ug/ml, HANP is non-toxic and could effectively promote osteoporotic osteoblast differentiation, as well as bone integration process. Materials delivering HANP would be a promising solution for osteoporotic bone nonunion. National Science and Technology Supporting Project, Grant No. 2012BAI17B01

In vitro degradation of biodegradable polylactic acid/magnesium composites: Relevance of Mg particle shape

Absorbable medical devices must be developed in order to have an appropriate degradation rate in agreement with the healing rate of bone in the implantation site. In this work, biodegradable composites formed by a polylactic acid matrix reinforced with 10%wt. magnesium microparticles were processed and their in vitro degradation investigated during 28days. A joint analysis of the amount of H2 released, the changes in pH in buffered (PBS) and non-buffered media (distilled water), the variations in mass, microstructure and the mechanical performance of the specimens was developed. The main aim was to elucidate the relevance of Mg particles shape on tailoring the degradation kinetics of these novel composites. The results show that the shape of the Mg reinforcing particles plays a crucial role in the degradation rate of PLA/Mg composites, with spherical particles promoting a lower degradation rate than irregular particles. This fact is only partially due to the smaller surface area to volume ratio of the spherical particles. Irregular particles promote a faster formation of cracks and, therefore, an increasingly faster degradation of the polymeric matrix. In every case, the amount of H2 released by the composites was well below that released by monolithic Mg. The pH of PBS during degradation remained always within 7.2 and 7.4. PLA/Mg reinforced with spherical particles retains more than 90% of its mechanical properties after 7days of immersion and more than 60% after 28days. Statement of SignificanceThe increasing demand for temporary orthopaedic implants is the driving force to seek new strategies to decrease costs and simultaneously improve patients comfort as well as simplify surgical procedures. Resorbable medical devices must be developed in order to have an appropriate degradation rate in agreement with the healing rate of bone. We are presenting for the first time results of the degradation kinetics of a new material based on polylactic acid reinforced with 10%wt. Mg microparticles. This work analyzes the relevance of Mg particle shape (irregular and spherical) on tailoring the degradation behaviour of these composites. Conclusions withdrawn from this study help to customize bioabsorbable materials in order to meet the requirements for a specific application and patient.

Surveillance of Stem Cell Fate and Function: A System for Assessing Cell Survival and Collagen Expression In Situ.

Cell-based therapy is an emerging paradigm in skeletal regenerative medicine. However, the primary means by which transplanted cells contribute to bone repair and regeneration remain controversial. To gain an insight into the mechanisms of how both transplanted and endogenous cells mediate skeletal healing, we used a transgenic mouse strain expressing both the topaz variant of green fluorescent protein under the control of the collagen, type I, alpha 1 promoter/enhancer sequence (Col1a1(GFP)) and membrane-bound tomato red fluorescent protein constitutively in all cell types (R26(mTmG)). A comparison of healing in parietal versus frontal calvarial defects in these mice revealed that frontal osteoblasts express Col1a1 to a greater degree than parietal osteoblasts. Furthermore, the scaffold-based application of adipose-derived stromal cells (ASCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), and osteoblasts derived from these mice to critical-sized calvarial defects allowed for investigation of cell survival and function following transplantation. We found that ASCs led to significantly faster rates of bone healing in comparison to BM-MSCs and osteoblasts. ASCs displayed both increased survival and increased Col1a1 expression compared to BM-MSCs and osteoblasts following calvarial defect transplantation, which may explain their superior regenerative capacity in the context of bone healing. Using this novel reporter system, we were able to elucidate how cell-based therapies impact bone healing and identify ASCs as an attractive candidate for cell-based skeletal regenerative therapy. These insights potentially influence stem cell selection in translational clinical trials evaluating cell-based therapeutics for osseous repair and regeneration.

Residents' journal review

Residents' journal review

Effects of low-level laser therapy on the expression of osteogenic genes during the initial stages of bone healing in rats: a microarray analysis.

This study evaluated the morphological changes produced by LLLT on the initial stages of bone healing and also studied the pathways that stimulate the expression of genes related to bone cell proliferation and differentiation. One hundred Wistar rats were divided into control and treated groups. Noncritical size bone defects were surgically created at the upper third of the tibia. Laser irradiation (Ga-Al-As laser 830nm, 30mW, 94s, 2.8J) was performed for 1, 2, 3, 5, and 7 sessions. Histopathology revealed that treated animals produced increased amount of newly formed bone at the site of the injury. Moreover, microarray analysis evidenced that LLLT produced a significant increase in the expression TGF-β, BMP, FGF, and RUNX-2 that could stimulate osteoblast proliferation and differentiation, which may be related to improving the deposition of newly formed bone at the site of the injury. Thus, it is possible to conclude that LLLT improves bone healing by producing a significant increase in the expression of osteogenic genes.

The effect of acemannan sponges in post-extraction socket healing: A randomized trial

ObjectiveThe aim of this study was to investigate the effect of acemannan, a polysaccharide extracted from Aloe vera gel, on tooth socket healing, 3 months after surgical removal of mandibular partial bony impacted third molars. Materials and methodsNinety-nine volunteers (18–24 years old) participated in this random controlled trial. After surgical removal, the sockets were randomly divided into acemannan sponge treated and non-treated control groups. Periapical radiographs of the socket were obtained immediately and after 3-month post-surgery. The bone-healing rate was evaluated by (i) the percentage radiographic density of formed bone in the socket and (ii) the change in percentage radiographic density of formed bone in the socket. ResultsNo adverse effects or dry sockets were experienced by any of the subjects. The percentage radiographic density of the sockets at 3-month post-surgery in the acemannan-treated group was significantly greater than control (p<0.01). The change in percentage radiographic density of the acemannan-treated group was also significantly higher than that of the control (p<0.05). ConclusionAt 3-month post-surgery, acemannan increased the bone density and tooth socket healing of mandibular partial bony impacted third molars.

Longitudinal analysis of osteogenic and angiogenic signaling factors in healing models mimicking atrophic and hypertrophic non-unions in rats.

Impaired bone healing can have devastating consequences for the patient. Clinically relevant animal models are necessary to understand the pathology of impaired bone healing. In this study, two impaired healing models, a hypertrophic and an atrophic non-union, were compared to physiological bone healing in rats. The aim was to provide detailed information about differences in gene expression, vascularization and histology during the healing process. The change from a closed fracture (healing control group) to an open osteotomy (hypertrophy group) led to prolonged healing with reduced mineralized bridging after 42 days. RT-PCR data revealed higher gene expression of most tested osteogenic and angiogenic factors in the hypertrophy group at day 14. After 42 days a significant reduction of gene expression was seen for Bmp4 and Bambi in this group. The inhibition of angiogenesis by Fumagillin (atrophy group) decreased the formation of new blood vessels and led to a non-healing situation with diminished chondrogenesis. RT-PCR results showed an attempt towards overcoming the early perturbance by significant up regulation of the angiogenic regulators Vegfa, Angiopoietin 2 and Fgf1 at day 7 and a further continuous increase of Fgf1, -2 and Angiopoietin 2 over time. However µCT angiograms showed incomplete recovery after 42 days. Furthermore, lower expression values were detected for the Bmps at day 14 and 21. The Bmp antagonists Dan and Twsg1 tended to be higher expressed in the atrophy group at day 42. In conclusion, the investigated animal models are suitable models to mimic human fracture healing complications and can be used for longitudinal studies. Analyzing osteogenic and angiogenic signaling patterns, clear changes in expression were identified between these three healing models, revealing the importance of a coordinated interplay of different factors to allow successful bone healing.

The effects of amlodipine and platelet rich plasma on bone healing in rats.

AimThe aim of this study was to evaluate the effects of calcium channel blocker (CCB) amlodipine (AML), platelet rich plasma (PRP), and a mixture of both materials on bone healing.Materials and methodsFifty-six male Wistar rats were randomly divided into four groups: group A, tibia defect model with no treatment; group B, tibia defect model treated with AML, 0.04 mg daily by oral gavage; group C, tibia defect model treated with local PRP; group D, tibia defect model treated with local PRP and AML, 0.04 mg daily by oral gavage.ResultsAt day 21, bone healing was significantly better in groups C and D compared to group A (P<0.05), but comparisons showed no statistically significant difference in group B (P>0.05). At day 30, groups B and C showed no statistically significant difference (P>0.05) compared to group A, but bone healing in group D was significantly better than in group A (P<0.05). Statistically, AML did not affect alkaline phosphatase (ALP) activity at 21 and 30 days (P>0.05), but PRP and AML + PRP increased ALP activity statistically (P<0.05).ConclusionIt can be concluded that AML had neither a positive nor a negative effect on bone healing, but when used in combination with PRP, it may be beneficial.

Effect of soft-tissue attachment on tibial fracture healing in rats.

To compare tibial fracture healing in rats with or without soft-tissue attachment. The left tibias of 30 Wistar rats were osteotomised and equally randomised into 3 groups. In the avascular segmental fracture group, an 8-mm bone segment were first removed and then immediately put back. In the vascular segmental fracture group, the 8-mm bone segment was not displaced, with periosteal and muscular attachments. In the simple fracture group, a simple fracture in the middle tibia was made. All tibias were then stabilised with an intramedullary nail through the patellar tendon, and the wound was closed with sutures. After 8 weeks, all left tibias and 9 of the intact right tibias were harvested. Bone mineral content and density of the calluses were assessed using dual energy X-ray absorptiometry scanning. The maximum torsional strength, rigidity, and energy to failure of the tibias were measured. All tibias healed (callus formation), without mal-union or pin migration. The 3 groups did not differ significantly in terms of torsional strength, rigidity, energy to failure, bone mineral content, and bone mineral density. The mean torsional strength of the 9 intact tibias was significantly higher than the healed tibias (14.9 vs. 10.6 Nmm, p=0.021). Soft-tissue detachment from bone segments did not impair bone healing in rats.

The influence of low-level laser therapy with alendronate irrigation on healing of bone defects in rats.

The aim of this study was to investigate the effects of alendronate (Aln) irrigation with low-level laser therapy (LLLT) on the healing of bone defects in rats. Sixty Wistar rats weighing 250 to 300 g were randomly divided into three groups of 20 animals each: (1) control group, (2) Aln group, and (3) Aln with LLLT group. The distal epiphysis of all rats was perforated with a surgical bone drill. Twenty rats served as control. The bone defects of 40 rats received local alendronate sodium trihydrate irrigation (1 mg/ml) at the time of surgery. LLLT was applied to the bone defects of 20 rats immediately after Aln irrigation, and repeated on days 2, 4, 6, and 8 with a total dose of 10 J/cm(2) (2 J/cm(2) × 5). Continuous wave of GaAlAs laser (808 nm) was used with a power density of 0.1 W/cm(2). Laser energy was applied for 20 s (0.1 W × 20 s/1 cm(2)) per session. Control group, Aln group, and Aln with LLLT group rats were sacrificed at days 10 and 20 to compare the bone healing of each group histologically. There were significant differences between the three groups regarding union, substantia spongiosa, cortex formation, and in sum of histologic scores on days 10 and 20 (P < 0.0001). Our findings demonstrated that Aln has a more positive effect with LLLT on bone healing in rats. It was concluded that combining LLLT (808 nm laser at 10 J/cm(2)) with Aln irrigation has a beneficial effect in bone repair. It was demonstrated experimentally that Aln irrigation during the surgery had a significant effect to enhance bone formation, and LLLT significantly potentiated the osseous healing effects of Aln on bone defects. This administration method is able to minimize the dose of Aln in order to avoid both systemic and local adverse effects as well as the local injection times during the bone healing process.

Additional bone graft accelerates healing of clavicle non-unions and improves long-term results after 8.9years: a retrospective study.

BackgroundClavicle non-unions can occur after both conservative and operative treatment failure. Here, we investigated the outcome of patients with delayed fracture healing or non-unions of the clavicle. Patients underwent revision surgery by plate osteosynthesis of the clavicle with or without bone grafting. Our aim was to determine rates of bone healing and the functional long-term outcome.MethodsThe study population of 58 consecutive patients was divided into group 1 (n = 25; no bone graft) and group 2 (n = 33; iliac crest bone graft). Bone consolidation was determined by the Lane-Sandhu score preoperatively and after 2.2 ± 1.8 years, respectively. The functional long-term outcome was determined after 8.9 ± 2.7 years in all available patients (n = 30) by the Constant score, DASH (Disabilities of the Arm, Shoulder and Hand) score and SF-36, and clavicle length was measured by ultrasound as compared to the healthy side.ResultsClavicle consolidation was achieved in 54 out of 58 patients (93.1%) after revision surgeries. The radiographic score and bone consolidation rates were significantly higher in group 2 (93.3%) as compared with 72% in group 1 (p = 0.02), resulting in a significantly shorter time to bone consolidation in group 2. Similarly, the relative risk for additional surgery after the first revision surgery was 4.7-fold higher in group 1 (p = 0.02). The long-term results showed overall very good results in DASH score (14.9 ± 16.5) and good results in Constant scores (77.9 ± 19.9). The group analyses found significantly better Constant scores and better visual analogue pain scale (VAS) numbers in group 2. Clavicle shortening appeared to affect the clinical results, and a mild correlation between shortening and Constant scores (R = −0.31) was found.ConclusionsThis study shows high rates of bone healing and good functional outcomes after surgical revision of clavicle non-unions and further demonstrates that additional bone graft could significantly accelerate bone healing. This indicates that revision surgery of clavicle non-unions might preferably be done with additional bone graft, even if the surgeon considers that bone healing might be achieved without bone grafting.

Traumatic brain injury result in accelerated fracture healing: A Rat Model

Background: In patients who have sustained a traumatic brain injury with an associated extremity fracture there is often a clinical perception that the rate of new bone formation around the fracture site is increased. In this study, we made a rat model of femoral fracture to investigate the serum factors changes in vivo. We examined the effects serum factors on fracture healing and the molecular signaling pathways that might link these two. Methods and Findings: Thirty-Six female Sprague-Dawley rats were randomly allocated into 4 groups; the non-operated control group, traumatic brain injury (TBI) group, bone fracture (Fr) group and the bone fracture/ TBI group (TBI & Fr) (n=9 per group). These animals were sacrificed at 6 weeks after experiments. Volume of callus in fracture was measured weekly with the Perkins volume formula at 2nd week after operation. The radiology imaging was interpreted by two or more senior orthopedic specialists. In vivo chemo taxis assay by serum samples collected at the 1, 3, 7 and 14 days, and 3rd, 4th, 6th week after surgery. Seral NGF, Wnt, RANKL, Dkk-1, ACTH, Leptin titer was measured and analyzed. After 2 weeks operation, the formation of callus was found at the fracture site, callus in TBI & Fr group was slightly higher than Fr group; however, there was no significant difference existed between the TBI & Fr and Fr groups. The ACTH level was significantly elevated in the TBI & Fr group than other groups and attained its peak at 1 week after operation, while the leptin was shown higher levels in Fr groups than TBI and TBI & Fr groups at 2 weeks after operation. The serum insulin level was markedly increased in all experimental groups during 1-3 days after surgery; at the meanwhile, the serum glucose level only significantly increased in the Fx and TBI groups at the 1 and 3 day after operation. The serum of NGF levels in the groups with TBI process (TBI and TBI & Fr groups) was significantly higher than those of the simple fracture group and control group. In the early stage of bone fracture, DKK-1 should be more active than Wnt-3a and NGF; later Wnt-3a and NGF became active to stimulate the osteoblasts for bone formation. After 3 day to 2 week of surgery, the RANKL process was drove to additional bone remodeling in accompany with bone formation. Conclusions: Through this project, the pathogenesis of increased rates of excessive bone healing in the patients with traumatic brain injury will be elucidated for the future study on clinical treatment in both traumatic brain injury and fracture healing. Keywords: Traumatic brain injury, fracture healing,

Bisphosphonate associated osteomyelitis of the jaw in patients with bony exposure: prevention, a new way of thinking.

Objective There is strong evidence of a link between the use of systemic bisphosphonates (BPs) and osteonecrosis of the jaw, especially in cancer patients. Among risk factors for BRONJ, tooth extraction and immune suppressive drugs seem to have significant role on bone healing. Therefore, the importance of these parameters in development of BRONJ was reviewed in this retrospective study in two maxillofacial surgery units.Material and Methods From 2007 to 2012, 46 patients on bisphosphonate who had developed oral bony lesions participated in this study. The pharmacological exposure, comorbidities, maxillofacial findings, types of treatment and outcome data were collected from clinical and radiological records.Results The most frequently used BP was alendronate (67%). Tooth extraction was reported in 61% of patients with BRONJ. Systemic corticosteroids were prescribed in 35 cases (76%) as an adjuvant for BP. Patients on corticosteroids had a lower probability of bony lesion healing (p<0.05) than patients without corticosteroids. Of the 46 patients who underwent conservative treatments, only ten were completely healed (21%).Conclusions Beside tooth extraction, corticosteroids were shown to be an implant risk factor for low rate of bone healing and hence the development of BRONJ. The outcome of conservative treatment was uncertain and this emphasizes the importance of prevention.

Reamed intramedullary exchange nailing: treatment of choice of aseptic femoral shaft nonunion.

BackgroundThe aim of this study was to evaluate a standardized method of treatment of femoral nonunion of the isthmal femur excluding non-united metaphyseal fractures.MethodsBetween 2003 and 2010, 72 consecutive patients with nonunion of the femoral shaft were operated using a standardized protocol in our trauma department and followed up for successful union and functional result.ResultsOsseous healing was observed in 71 patients (98%). Only one patient was lacking bone healing following a time period of 24 months after the first exchange nailing and 5 months after the second exchange nailing. In 59 patients (82%), uneventful and timely bone healing after exchange nailing was detected. In 18% of patients (n = 13), delayed bone healing was observed and required additional therapy. In the majority of patients (61%), bone healing occurred within the first 2 to 5 months, only 18% of patients’ duration of bone healing exceeded 8 months. In 62 patients (86%), no relevant or clinically apparent leg-length discrepancy prior to and after exchange nailing was detected as well as no significant axis deviation or malrotation. Functional studies including simple clinical gait and standing analysis, return to activities of daily life, return to sports activities, and return to work were all reached on a satisfying level.DiscussionReamed intramedullary exchange nailing as described in this study is the treatment of choice for aseptic femoral shaft nonunion with a high rate of bone healing and a low rate of complications including length discrepancy or malrotation and a good functional outcome.

Inchiodamento tibiale con accesso sovrarotuleo mininvasivo

Intramedullary nailing is the “gold standard” in the treatment of shaft tibial fractures. It provides high rates of bone healing. We analyzed the advantages of intramedullary nailing using a suprapatellar approach, which reduces the risk of DVT and makes patient management in the operating room easier.

Laminoplasty and laminectomy hybrid decompression for the treatment of cervical spondylotic myelopathy with hypertrophic ligamentum flavum: a retrospective study.

ObjectiveTo report the outcomes of a posterior hybrid decompression protocol for the treatment of cervical spondylotic myelopathy (CSM) associated with hypertrophic ligamentum flavum (HLF).BackgroundLaminoplasty is widely used in patients with CSM; however, for CSM patients with HLF, traditional laminoplasty does not include resection of a pathological ligamentum flavum.MethodsThis study retrospectively reviewed 116 CSM patients with HLF who underwent hybrid decompression with a minimum of 12 months of follow-up. The procedure consisted of reconstruction of the C4 and C6 laminae using CENTERPIECE plates with spinous process autografts, and resection of the C3, C5, and C7 laminae. Surgical outcomes were assessed using Japanese Orthopedic Association (JOA) score, recovery rate, cervical lordotic angle, cervical range of motion, spinal canal sagittal diameter, bone healing rates on both the hinge and open sides, dural sac expansion at the level of maximum compression, drift-back distance of the spinal cord, and postoperative neck pain assessed by visual analog scale.ResultsNo hardware failure or restenosis was noted. Postoperative JOA score improved significantly, with a mean recovery rate of 65.3±15.5%. Mean cervical lordotic angle had decreased 4.9 degrees by 1 year after surgery (P<0.05). Preservation of cervical range of motion was satisfactory postoperatively. Bone healing rates 6 months after surgery were 100% on the hinge side and 92.2% on the open side. Satisfactory decompression was demonstrated by a significantly increased sagittal canal diameter and cross-sectional area of the dural sac together with a significant drift-back distance of the spinal cord. The dural sac was also adequately expanded at the time of the final follow-up visit.ConclusionHybrid laminectomy and autograft laminoplasty decompression using Centerpiece plates may facilitate bone healing and produce a comparatively satisfactory prognosis for CSM patients with HLF.

Adipose‐Derived Stem Cells Combined With Inorganic Bovine Bone in Calvarial Bone Healing in Rats With Type 2 Diabetes

Clinical studies have revealed that patients with type 2 diabetes mellitus (DM) have higher implant and bone grafting failure rates than the general population, likely owing to inferior bone healing. The authors sought to investigate whether adipose-derived stem cells (ASCs) combined with inorganic bovine bone improves bone repair in calvarial vertical critical-sized defects (CSDs) in rats with type 2 DM. Bovine bone alone or seeded with 3 × 10(5), 3 × 10(6), or 3 × 10(7) ASCs/graft was randomly transplanted into calvarial CSDs in rats with DM induced by a high-fat diet with low-dose streptozotocin. Specimens were assayed using microcomputed tomography and histomorphometry at 4 and 8 weeks postimplantation. The histologic results showed an increase in new bone formation in the experimental groups compared with the control group. Both bone volume/total volume and trabecular thickness of newly formed bone within CSDs were the highest, and trabecular spacing was the lowest, in the 3 × 10(6) group at 8 weeks for the most favorable outcome. The results showed that the amount of new bone was greatest in the 3 × 10(6) group by 8 weeks. ASCs enhanced vertical bone regeneration in calvarial defects in rats with type 2 DM, when used in association with bovine bone scaffolds. The findings suggest that a combination of ASCs and bovine bone scaffolds could improve bone quantity in vertical bone defects.

Effects of Calcium Phosphate/Chitosan Composite on Bone Healing in Rats: Calcium Phosphate Induces Osteon Formation

Vascularization of an artificial graft represents one of the most significant challenges facing the field of bone tissue engineering. Over the past decade, strategies to vascularize artificial scaffolds have been intensively evaluated using osteoinductive calcium phosphate (CaP) biomaterials in animal models. In this work, we observed that CaP-based biomaterials implanted into rat calvarial defects showed remarkably accelerated formation and mineralization of new woven bone in defects in the initial stages, at a rate of ∼60 μm/day (0.8 mg/day), which was considerably higher than normal bone growth rates (several μm/day, 0.1 mg/day) in implant-free controls of the same age. Surprisingly, we also observed histological evidence of primary osteon formation, indicated by blood vessels in early-region fibrous tissue, which was encapsulated by lamellar osteocyte structures. These were later fully replaced by compact bone, indicating complete regeneration of calvarial bone. Thus, the CaP biomaterial used here is not only osteoinductive, but vasculogenic, and it may have contributed to the bone regeneration, despite an absence of osteons in normal rat calvaria. Further investigation will involve how this strategy can regulate formation of vascularized cortical bone such as by control of degradation rate, and use of models of long, dense bones, to more closely approximate repair of human cortical bone.

Analysis of MRI signal changes in the adjacent pedicle of adolescent patients with fresh lumbar spondylolysis

The purpose of this study is to investigate a discrepancy between MRI and computed tomography (CT) findings in the spinal level distribution of spondylolysis. Recent advances in MRI have led to the early diagnosis of spondylolysis. Therefore, bony healing can be expected before the condition has a chance to worsen. In this study, we used MRI to examine the changes in spinal level signals in the pedicles adjacent to the pars interarticularis in adolescents with fresh lumbar spondylolysis. We then compared spinal level distribution of spondylolysis with that of previous results obtained by multidetector CT. The study included 98 adolescent patients (31 women and 67 men; mean age, 13.6 years; age range, 9-18 years) with fresh lumbar spondylolysis who showed MRI signal changes in the adjacent pedicle. An MRI signal change was defined as a high signal change on fat-suppressed imaging. MRI signal changes were detected in 150 adjacent pedicles of 101 vertebrae. Of these vertebrae, MRI signal changes in only 67 (66.3%) corresponded to L5, while changes in 34 (33.7%) corresponded to L3 or L4. In our follow-up study, the bone-healing rate with no vertebral defect was 100% at L3, 97.1% at L4, and 84.4% at L5. In addition, 11 of 34 (32.4%) vertebrae with signal changes at L3 or L4 occurred with L5 terminal-stage spondylolysis (no MRI signal change). MRI revealed a higher prevalence of L3 or L4 spondylolysis than observed with CT.