Polymethylmethacrylate Spacer Research Articles

EXPERIMENTAL FAILURE OF HIP ARTHROPLASTY UNDER TORSION LOADING

Polymethylmethacrylate (PMMA) bone cement is strong in compression, however it tends to fail under torsion. Sufficient pressurisation and subsequent interdigitation between cement and bone are critical for the mechanical interlock of cemented orthopaedic implants, and an irregular surface on the acetabular cup is necessary for reasonable fixation at the cup-cement interface. There is limited literature investigating discrepancies in the failure mechanisms of cemented all-polyethylene acetabular cups with and without cement spacers, under torsional loading.In vitro experimental comparison of three groups of polyethylene acetabular prosthesis (PAP) cemented into prepared sawbone hemipelvises:* PAP without PMMA spacers maintaining an equal cement mantle circumferentially. (Group 1 n=3)* PAP without PMMA spacers cemented deliberately ‘bottoming-out’ the implant within the acetabulum. (Group 2 n=3)* PAP with PMMA spacers. (Group 3 n=3)The constructs were tested to torstional failure on a custom designed setup, and statistical analysis done by a one-way ANOVA and Tukey-Welsh test.Group 3 demonstrated superior torsional resistance with a statistically significant torque of 145Nm (SD±12Nm) at failure, compared to group 2 (109Nm, SD±7Nm) and group 1 (99Nm, SD±8Nm). Group 3 experienced failure predominantly at the bone-cement interface, in contrast, Groups 1 and 2 exhibited failure predominantly at the cup-cement interface. There was no significant difference between Group 1 and 2. Qualitative analysis of the failure mode indicates the efficient redistribution of stress throughout the cement mantle, consistent with the greater uniformity of cement.PMMA spacers increase the resistance to torsional failure at the implant-cement interface. Acetabular components without spacers (Groups 1 and 2) failed at the implant-cement interface before the cement-bone interface, at a statistically significantly lower level of torque to failure. Although the PMMA spacers may reduce cement interdigitation at the cement-bone interface the torsional forces required to fail are likely supraphysiological.

Differences in macrophage expression in induced membranes by fixation method – Masquelet technique using a mouse's femur critical-sized bone defect model

IntroductionMasquelet's induced membrane technique (MIMT) is an emerging method for reconstructing critical-sized bone defects. However, an incomplete understanding of the underlying biological and physical processes hinders further optimization. This study investigated the effect of different bone-defect fixation methods on macrophage expression in an induced membrane using a novel mouse plate-fixed Masquelet model. MethodsMice were divided into Plate-fixed Masquelet (P-M), Intramedullary-fixed Masquelet (IM-M), Plate-fixed Control (P-C), and Back subfascial (B) groups. In the P-M and IM-M groups, a polymethylmethacrylate (PMMA) spacer was implanted into a 3 mm bone defect, while the defect in the P-C group remained unfilled. In group B, a spacer was inserted under the back fascia to examine membrane formation caused by a simple foreign body reaction. Tissues were collected at 1, 2, and 4 weeks postoperatively. Hematoxylin and eosin (H&E) staining and immunohistochemistry (CD68 and CD163: macrophage markers) were performed to assess macrophage expression within the membrane. qPCR was performed to measure the expression of CD68, CD163, and fibroblast growth factor 2 (FGF2). ResultsFour weeks post-operation, the P-M group presented with minimal callus growth, whereas the IM-M group exhibited vigorous growth. The P-M and IM-M groups displayed a tri-layered membrane structure, which is consistent with the results of previous studies. The IM-M group had significantly thicker membranes, whereas the P-M group exhibited higher expression levels of CD68, CD163, and FGF2. Group P-C showed no osteogenesis, whereas group B maintained a thin, cell-dense membrane structure. The P-M group consistently showed higher gene expression levels than the P-C and P-B groups. ConclusionThis study introduced a mouse plate fixation model for MIMT. The induced membranes could be adequately evaluated in this model. Induced membranes are formed by foreign body reactions to PMMA spacers; however, their properties are clearly different from those of simple foreign body reaction capsules and granulation tissues that infiltrate bone defects, suggesting that they are more complex tissues. The characteristics and expression of macrophages within these induced membranes varied according to the bone defect fixation method.

A NOVEL TECHNIQUE FOR MANAGEMENT OF A CRITICALLY-SIZED BONE DEFECT IN THE OPEN PROXIMAL TIBIAL FRACTURE: EMPLOYING THE CAPANNA TECHNIQUE IN TRAUMA

A NOVEL TECHNIQUE FOR MANAGEMENT OF A CRITICALLY-SIZED BONE DEFECT IN THE OPEN PROXIMAL TIBIAL FRACTURE: EMPLOYING THE CAPANNA TECHNIQUE IN TRAUMA

Patient-specific articulating spacer for two-stage shoulder arthroplasty exchange.

Two-stage exchange with anantibiotic-loaded polymethylmethacrylate (PMMA) spacer is standard treatment for chronic periprosthetic joint infection of the shoulder. We present asafe and simple technique for patient-specific spacer implants. (Chronic) periprosthetic joint infection of the shoulder. Known allergy against components of PMMA bone cements. Inadequate compliance for two-stage exchange. Patient is unfit to undergo two-stage exchange. Hardware removal, histologic and microbiologic samples, and debridement. Preparation of targeted or calculated antibiotic-loaded PMMA. Tailoring of patient-specific spacer. Spacer implantation. Rehabilitation protocol. Antibiotic treatment. Reimplantation after successful eradication of infection.

BONE DEFECT HEALING USING THE INDUCED MEMBRANE TECHNIQUE AFTER CHRONICALLY INFECTED NONUNION IN A NOVEL RABBIT MODEL

In chronically infected fracture non-unions, treatment requires extensive debridement to remove necrotic and infected bone, often resulting in large defects requiring elaborate and prolonged bone reconstruction. One approach includes the induced membrane technique (IMT), although the differences in outcome between infected and non-infectious aetiologies remain unclear. Here we present a new rabbit humerus model for IMT secondary to infection, and, furthermore, we compare bone healing in rabbits with a chronically infected non-union compared to non-infected equivalents.A 5 mm defect was created in the humerus and filled with a polymethylmethacrylate (PMMA) spacer or left empty (n=6 per group). After 3 weeks, the PMMA spacer was replaced with a beta-tricalcium phosphate (chronOs, Synthes) scaffold, which was placed within the induced membrane and observed for a further 10 weeks. The same protocol was followed for the infected group, except that four week prior to treatment, the wound was inoculated with Staphylococcus aureus (4×106 CFU/animal) and the PMMA spacer was loaded with gentamicin, and systemic therapy was applied for 4 weeks prior to chronOs application.All the animals from the infected group were culture positive during the first revision surgery (mean 3×105 CFU/animal, n= 12), while at the second revision, after antibiotic therapy, all the animals were culture negative. The differences in bone healing between the non-infected and infected groups were evaluated by radiography and histology. The initially infected animals showed impaired bone healing at euthanasia, and some remnants of bacteria in histology. The non-infected animals reached bone bridging in both empty and chronOs conditions.We developed a preclinical in vivo model to investigate how bacterial infection influence bone healing in large defects with the future aim to explore new treatment concepts of infected non-union.

Treatment of Fracture-Related Infections with Bone Abscess Formation after K-Wire Fixation of Pediatric Distal Radius Fractures in Adolescents—A Report of Two Clinical Cases

Closed reduction and K-wire fixation of displaced distal radius fractures in children and adolescents is an established and successful surgical procedure. Fracture-related infections after K-wire fixation are rare but can have significant consequences for the patient. There is a lack of literature on the treatment of K-wire-associated fracture-related infections in children and adolescents. Herein, we report two cases of fracture-related infection after initial closed reduction and Kirschner wire fixation in two adolescents. One 13-year-old boy and one 11-year-old girl were seen for fracture-related infections 4 and 8 weeks after closed reduction and percutaneous K-wire fixation of a distal radius, respectively. X-ray and magnetic resonance imaging (MRI) revealed a healed fracture with osteolytic changes in the metaphyseal radius with periosteal reaction and abscess formation of the surrounding soft tissue structures. A two-staged procedure was performed with adequate debridement of the bone and dead space management with an antibiotic-loaded polymethyl methacrylate (PMMA) spacer at stage 1. After infection control, the spacer was removed and the defect was filled with autologous bone in one case and with a calcium sulphate-hydroxyapatite biomaterial in the other case. In each of the two patients, the infection was controlled and a stable consolidation of the distal radius in good alignment was achieved. In one case, the epiphyseal plate was impaired by the infection and premature closure of the epiphyseal plate was noted resulting in a post-infection ulna plus variant. In conclusion, a fracture-related infection after Kirschner wire fixation of pediatric distal radius fractures is a rare complication but can occur. A two-stage procedure with infection control and subsequent bone defect reconstruction was successful in the presented two cases. Premature closure of the epiphyseal growth plate of the distal radius is a potential complication.

Efficacy of Cefazolin Versus Vancomycin Antibiotic Cement Spacers.

Cefazolin is a heat-labile antibiotic that is not usually added to polymethylmethacrylate (PMMA) cement spacers because it is believed to be inactivated by the high polymerization temperatures. The purpose of this study was to compare cefazolin versus vancomycin high-dose antibiotic cement spacers. High-dose antibiotic PMMA spacers with either cefazolin or vancomycin were fabricated. Setting time, compressive strength, and compression modulus of spacers were measured. Spacers were emerged in saline, and the eluent was tested on days 1, 2, 3, 7, 14, and 30 to determine the zone of inhibition of methicillin-sensitive Staphylococcus aureus and estimate the cumulative antibiotic released. Cefazolin, compared with vancomycin-loaded spacers, had significantly shorter setting time [mean difference (MD) -1.8 minutes, 95% confidence interval (CI), -0.6 to -3.0], greater compressive strength (MD 20.1 megapascal, CI, 15.8 to 24.5), and compression modulus (MD 0.15 megapascal, CI, 0.06 to 0.23). The zone of inhibition of eluent from PMMA-C spacers was significantly greater than PMMA-V spacers at all time points, an average of 11.7 ± 0.8 mm greater across time points. The estimated cumulative antibiotic released from cefazolin spacers was significantly greater at all time points ( P < 0.0001). Cefazolin was not inactivated by PMMA polymerization and resulted in spacers with superior antimicrobial and biomechanical properties than those made with vancomycin, suggesting that cefazolin could play a role in the treatment of infected bone defects with high-dose antibiotic PMMA spacers.

Effectiveness of two-stage revision with commercial polymethylmethacrylate articulated hip spacer: similar outcomes against monomicrobial and polymicrobial hip periprosthetic joint infections.

Background: orthopaedic surgeons still struggle against a devastating complication - periprosthetic joint infection (PJI). A two-stage revision is considered the gold standard for chronic PJI for several authors, with success rates over 90 %. This strategy implies the remotion of the prosthesis and the implantation of an antibiotic-impregnated cement spacer in the joint. The primary objective of this study was to assess the effectiveness of a two-stage revision approach using a commercial prefabricated antibiotic-impregnated cement hip spacer for the treatment of hip PJI regarding monomicrobial and polymicrobial infections. Secondly, to assess risk factors for failure of two-stage revision. Material and methods: we conducted a retrospective study on patients that underwent revision of total hip arthroplasty (THA) between January2002 and January20218. We included adult patients with a diagnosis of chronic hip PJI that underwent two-stage revision using a prefabricated gentamicin-impregnated cement of polymethylmethacrylate (PMMA) hip spacer. We assessed whether it was monomicrobial or polymicrobial infections and comorbidities. Treatment success was defined when eradication of the infection was observed and no further procedures or mortality were registered after the second stage. Persistence or recurrence of infection was considered a failure of treatment. Results: the final series consisted of 84patients treated with the same hip spacer: 60 (71.4 %) monomicrobial and 24 (28.6 %) polymicrobial joint infections with an overall follow-up of 59.0 (36.0-84.0) months. The overall success rate was 90.5 %. Eight (9.5 %) patients failed. Smoking and BMI greater than 30 m kg were identified independent risk factors for failure in multivariate analysis. Conclusion: our study suggests that prefabricated gentamicin-impregnated PMMA spacer is an effective tool for the treatment of PJI, achieving similar outcomes whether it is monomicrobial or polymicrobial infections. Randomized prospective studies are needed to obtain more reliable conclusions.

Antibiotic release from PMMA spacers and PMMA beads measured with ELISA: Assessment of in vitro samples and drain fluid samples of patients.

For prosthetic joint infections, antibiotic loaded poly methyl methacrylate (PMMA) spacer or beads can be used to release high concentrations of antibiotics locally at the infection site, while minimizing systemic toxicity.The aim of this study is to determine in vitro and in vivo pharmacokinetic release profile of antibiotics from PMMA spacers and PMMA beads.For the in vitro experiment, the PMMA spacers or beads were submerged in phosphate-buffered saline and gentamicin concentrations were determined from collected specimen at several times points, measured with enzyme-linked immunosorbent assays(ELISA).To assess the in vivo antibiotic release profile of different spacers, wound drainage fluid samples were collected after implantation of a spacer over a period of maximum 14 days.After 48 h, the burst gentamicin concentration elution was 9862 ± 1782 ng/ml (mean ± SD) from spacers versus 38,394 ± 7071 ng/ml (mean ± SD) for beads. Over 35 days, spacers had eluted a cumulative mean concentration of 13,812 ± 3548versus 55,048 ± 12,006 ng/ml for beads (p < 0.001). Clinical samples of patients with a Vancogenx® spacer showed higher gentamicin release than Refobacin™ spacers (p < 0.001).This is the first study that measured the release data of local antibiotics with ELISA. Compare to spacers, the exact release values of gentamicin from PMMA beads are more than 10 times higher and reached a maximum much later than spacers. This makes the use of PMMA beads more preferable to use for treatment of the infection itself.

Mechanical strength of antibiotic-loaded PMMA spacers in two-stage revision surgery

BackgroundAntibiotic-loaded polymethylmethacrylate (PMMA) bone cement spacers provide high local antibiotic concentrations and patient mobility during the interim period of two-stage revision for periprosthetic joint infection (PJI). This study compares mechanical characteristics of six dual antibiotic-loaded bone cement (dALBC) preparations made from three different PMMA bone cements. The study`s main objective was to determine the effect of time and antibiotic concentration on mechanical strength of dALBCs frequently used for spacer fabrication in the setting of two-stage revision for PJI.MethodsA total of 84 dual antibiotic-loaded bone cement specimens made of either Copal spacem, Copal G + V or Palacos R + G were fabricated. Each specimen contained 0.5 g of gentamicin and either 2 g (low concentration) or 4 g (high concentration) of vancomycin powder per 40 g bone cement. The bending strength was determined at two different timepoints, 24 h and six weeks after spacer fabrication, using the four-point bending test.ResultsPreparations made from Copal G + V showed the highest bending strength after incubation for 24 h with a mean of 57.6 ± 1.2 MPa (low concentration) and 50.4 ± 4.4 MPa (high concentration). After incubation for six weeks the bending strength had decreased in all six preparations and Palacos R + G showed the highest bending strength in the high concentration group (39.4 ± 1.6 MPa). All low concentration preparations showed superior mechanical strength compared to their high concentration (4 g of vancomycin) counterpart. This difference was statistically significant for Copal spacem and Copal G + V (both p < 0.001), but not for Palacos R + G (p = 0.09).ConclusionsThis study suggests that mechanical strength of antibiotic-loaded PMMA bone cement critically decreases even over the short time period of six weeks, which is the recommended interim period in the setting of two-stage revision. This potentially results in an increased risk for PMMA spacer fracture at the end of the interim period and especially in patients with prolonged interim periods. Finally, we conclude that intraoperative addition of 4 g of vancomycin powder per 40 g of gentamicin-premixed Palacos R + G (Group D) is mechanically the preparation of choice if a dual antibiotic-loaded bone cement spacer with high antibiotic concentrations and good stability is warranted. In any case the written and signed informed consent including the off-label use of custom-made antibiotic-loaded PMMA bone cement spacers must be obtained before surgery.

Periosteal preservation: a new technique in resection of bone high-grade malignant tumors in children—about eleven cases

ObjectiveThe purpose of this study was to describe a surgical technique of bone resection with periosteal preservation and reconstruction in patients with high-grade bone malignant tumors and to determine its effect on local recurrences, and time and quality of bone union in bone autografting reconstruction.Patients and methodsWe retrospectively reviewed 11 cases of high-grade malignant bone tumors in children aged 4 to 16 years, who were treated with chemotherapy and tumor resection while preserving partially the adjacent periosteum. Tumors were located in the lower limb in eight cases; three tumors were in the humerus. The mean length of the bone defect after resection was 15.8 cm (range, 6–34.5 cm). Reconstruction was provided by non-vascularized autograft in eight cases (lower limb) and polymethyl methacrylate spacer in three cases (upper limb). Patients were followed up for a mean of 71 months.ResultsAt the last follow-up, no patients had local recurrence. Three patients were dead because of metastasis. Bone union was good in time and quality in all children who had bone autografting. In cases of PMMA reconstruction, there was periosteal bone formation around the spacer. According to the MSTS functional score, patients with lower limb localizations had a mean score of 27.75 points and patients with upper limb localizations had a score of 24/30.ConclusionPreservation of the periosteum in bone resection for malignant tumors could be a good adjuvant alternative for bone reconstruction, without increasing the risk of local recurrence. However, patients must be carefully selected.

Use of antibiotic-impregnated beads in the treatment of lumbosacral surgical site infection: A retrospective case series

BackgroundDifferent adjuvant local-antibiotic techniques are described in management of surgical-site infections (SSIs). Antibiotic-laden polymethyl methacrylate (PMMA) spacers have been used in peri-prosthetic infections. However, their role in treatment of spinal SSIs is not well-recognised. MethodsAfter approval from Institutional Review Board, we retrospectively evaluated the data of patients aged≥18 years, who were treated for SSIs of lumbo-sacral region (2010–2019). Among them, those who underwent treatment with the placement of cement beads (temporarily/permanently) were identified. This approach was utilised for post-surgical spondylodiscitis patients with significant, associated infection or abscess involving the paraspinal musculature. Only those with≥2 years’ follow-up, were included.Patient demographic details, site of infection, details regarding laboratory/radiological investigations, management-protocol followed, pathogen grown, antibiotics used (their dosage and duration of use), complications encountered and outcome were recorded. Results13 patients [4 males, age:57.3 ± 12.4 years] were included. Seven had co-morbidities. One had upper-lumbar involvement, one sacral and others had lower-lumbar (L4/distally) disease. While 7 had recent-onset infection (≤2 months since primary surgery), 6 had chronic infection. In 2, 8, 2, and 1 patients, primary surgery was microdiscectomy, TLIF, PLF, and adult-deformity surgery, respectively.Nine underwent two-staged intervention and 4 underwent single procedure. Eleven had PMMA beads, while 2 underwent calcium sulphate bead insertion. Culture grew E coli in 3, Pseudomonas in 2; and E fecalis, K pneumoniae, MSSA and MRSA in one patient each. In 4 patients, beads were not removed. All patients underwent 2 weeks of parenteral antibiotics, followed by 8–12 weeks of oral medications. There was complete remission in all patients, except one who required additional VAC therapy. ConclusionLocal antibiotic-laden bead application is an effective adjuvant strategy (along with debridement and systemic antibiotics) for the treatment of spinal SSI, where there is substantial infection involving the paraspinal musculature. It is cost-effective and often necessitates second procedure for bead removal.

Bone regeneration after marginal bone resection in two-stage treatment of chronic long bone infection - a combined histopathological and clinical pilot study

IntroductionIn chronic bone infection, marginal bone resection avoids large and difficult to reconstruct bone defects. However, there is still a lack of knowledge on bone regeneration during chronic bone infection and bone healing capability after marginal bone resection. Therefore, the purpose of this study was to investigate the clinical and histopathological outcomes after marginal bone resection in chronic long bone infection. We hypothesized that there is a regenerative bone healing potential after marginal bone resection that results in an acceptable clinical outcome and improved pathohistological bone healing parameters during treatment. Materials and methodsNine patients were treated for chronic bone infections in a two-stage manner with marginal bone resection of the infected area and the placement of an antibiotic-loaded polymethyl methacrylate (PMMA) spacer at stage one followed by bone reconstruction at stage two combined with systemic antibiotic therapy. Comparable bone samples were harvested at the border region between vital and necrotic bone area during stage one and the identical location during stage two. Control bone samples were harvested from five healthy patients without bone infection. Clinical outcome in terms of infection eradication and bone consolidation were assessed. The phenotypic changes of osteocyte and morphological changes of lacunar-canalicular network were investigated by histological and immunohistochemical staining between the two observation periods. Furthermore, expression levels of major bone formation and resorption markers were investigated by immunohistochemical and tartrate-resistant acid phosphatase (TRAP) staining. ResultsThe clinical results with a follow-up of 12.9 months showed that eight of nine patients (88.9%) achieved bone consolidation after a planned two-stage procedure of marginal resection of necrotic bone and consecutive reconstruction. In four of the nine patients (44.4%), additional marginal debridements after stage two had to be performed. After marginal resection at stage one, the improved bone formation ability at stage two was demonstrated by significantly lower percentage of empty lacunae, significantly more mature osteocytes and higher BMP-2 positive cell density, whereas decreased resorption was indicated by significantly lower osteoclast density and RANKL/OPG ratio. In patients requiring additional debridement compared to patients without additional debridements, a significantly higher percentage of empty lacunae was found at stage one. ConclusionMarginal bone resection combined with local and systemic antibiotic therapy is a feasible treatment option to avoid large bone defects as bone from the marginal resection area seems to have good regenerative potential. Despite a high revision rate of 44.4%, this technique avoids large bone resection and revisions can be done by further marginal debridements.

Failure analysis of articulating polymethyl methacrylate spacers in two-stage revision total hip arthroplasty.

AimsTwo-stage exchange revision total hip arthroplasty (THA) performed in case of periprosthetic joint infection (PJI) has been considered for many years as being the gold standard for the treatment of chronic infection. However, over the past decade, there have been concerns about its safety and its effectiveness. The purposes of our study were to investigate our practice, collecting the overall spacer complications, and then to analyze their risk factors.MethodsWe retrospectively included 125 patients with chronic hip PJI who underwent a staged THA revision performed between January 2013 and December 2019. All spacer complications were systematically collected, and risk factors were analyzed. Statistical evaluations were performed using the Student's t-test, Mann-Whitney U test, and Fisher's exact test.ResultsOur staged exchange practice shows poor results, which means a 42% mechanical spacer failure rate, and a 20% recurrent infection rate over the two years average follow-up period. Moreover, we found a high rate of spacer dislocation (23%) and a low rate of spacer fracture (8%) compared to the previous literature. Our findings stress that the majority of spacer complications and failures is reflecting a population with high comorbid burden, highlighted by the American Society of Anesthesiology grade, Charlson Comorbidity Index, and Lee score associations, as well as the cardiac, pulmonary, kidney, or hepatic chronic conditions.ConclusionOur experience of a two-stage hip exchange revision noted important complication rates associated with high failure rates of polymethylmethacrylate spacers. These findings must be interpreted in the light of the patient’s comorbidity profiles, as the elective population for staged exchange has an increasing comorbid burden leading to poor results. In order to provide better results for this specific population, our conclusion suggests that comparative strategy studies are required to improve our therapeutic indication.Cite this article: Bone Jt Open 2022;3(6):485–494.

Unusual Presentation and Surgical Treatment of a Phosphaturic Mesenchymal Tumor in a Knee.

A 30-year-old woman presented to our hospital with an 11-year history of gradually enlarging masses around the left knee and 2-year history of progressively worsening bone pain. Tumor-induced osteomalacia (TIO), a rare paraneoplastic syndrome caused by phosphaturic mesenchymal tumors (PMTs) was suspected, but the postoperative pathology of her two operations was both reported as tenosynovial giant cell tumor (TGCT), making its diagnosis confusing. The possibility of hypophosphatemia, insufficient blood supply, innervation of the left lower limbs, as well as the unclear pathology, make it unreasonable to perform tumor-type knee prosthesis replacement directly. Finally, we placed static polymethylmethacrylate (PMMA) spacer at first, then when the concentration of blood phosphorus level rose to the normal range, the pathology was confirmed to be TIO, the blood supply and innervation was satisfying, tumor-type knee prosthesis replacement was performed. She was discharged post operative day 15 after the prothesis implantation without incident. One and a half years after her surgery, the concentration of blood phosphorus was still in the normal range, the symptom of systemic bone pain had improved significantly, the prosthesis was still in a good position and no recurrence was caught.

The induced membrane technique: Optimization of bone grafting in a rat model of segmental bone defect

IntroductionThe induced membrane technique (IMT) is a two-stage surgical procedure used to treat fracture nonunion and bone defects. Although there is an increasing number of animal studies investigating the IMT, few have examined the outcomes of bone healing after a second stage grafting procedure. This study aimed at comparing two bone grafting procedures, as part of the IMT, in order to establish a rat model providing consistent healing outcomes. MethodsIn male Fischer 344 rats, we created a 5 mm defect in the right femur, stabilized the bone with a plate and screws, and inserted a polymethylmethacrylate spacer into the defect. Four weeks later, the spacer was removed. Bone graft was harvested from a donor rat and placed into the defect, followed by membrane and wound closure. Experiments were conducted in two groups. In group 1 (n = 11), the bone graft contained a variable amount of cortical and cancellous bone, the time from donor euthanasia to grafting was up to 240 min, and one donor rat provided graft for 5-6 recipients. In group 2 (n = 12), we reduced the contribution of cortical bone to the graft, included bone marrow, and kept donor euthanasia to grafting time under 150 min. One donor was used per 3-4 recipients. The volume of graft per recipient and all other elements of the protocol were the same across groups. Bone healing at 12 weeks post grafting was compared radiographically by two orthopaedic surgeons in a blinded fashion, based on union status and a modified Lane & Sandhu score. ResultsHealing rates improved from 36.4% in Group 1 to 91.6% in Group 2. There was a significant relationship between the methods and resulting union status (p = 0.004). The odds of achieving full union were significantly higher in group 2 compared to group 1 (odds ratio=19.25, 95% confidence interval [1.77-209.55]; p = 0.009). The average radiographic score was also significantly higher in group 2 (p = 0.005). ConclusionThe revised bone grafting method significantly improved the healing outcomes and contributed to establishing a consistent rat model of the IMT. This model can benefit preclinical investigations by allowing for reliable and clinically-relevant comparisons.

Effects of PMMA spacer loaded with varying vancomycin concentrations on bone regeneration in the Masquelet technique

Whether antibiotics should be included remains greatly debated in Masquelet technique. This study intended to determine the effect of polymethyl methacrylate (PMMA) spacer loaded with different vancomycin concentrations on bone defect repair. Hollow cylindrical spacers consisting of PMMA and varying vancomycin concentrations (0, 1, 2, 4, 6, 8, and 10 g) were prepared. Critical bone defects of rabbits were created at the radial shaft, and spacers were implanted and subsequently intramedullary fixed with retrograde Kirschner’s wires (n = 4 for each vancomycin concentration). After 4 weeks, the induced membranes were opened and cancellous allografts were implanted into the defects. Eight weeks post-operatively, the results of X-ray, histology, and micro-CT revealed that some cortical bone was formed to bridge the gap and the bone marrow cavity was formed over time. Quantitatively, there was more new bone formation in the groups with a relatively lower vancomycin concentration (1–4 g) compared with that in the groups with a higher vancomycin concentration (6–10 g). Our findings suggested that PMMA spacers loaded with relatively lower vancomycin concentrations (1–4 g) did not interfere with new bone formation, whereas spacers loaded with relatively higher vancomycin concentrations (6–10 g) had negative effects on bone formation.

Efficacy of total flavonoids of Rhizoma drynariae on the blood vessels and the bone graft in the induced membrane

BackgroundTotal flavonoids of Rhizoma drynariae (TFRD), a Chinese medicine, is widely used in the treatment of orthopedic diseases. However, there are few basic and clinical studies on the effect of TFRD on induced membrane technique (Masquelet technique). PurposeThis trial is to explore effects of TFRD on vascularization of the induced membrane, and mineralization of the bone graft in rats with femoral bone defects. Study design and methodsForty-eight Sprague-Dawley rats were randomly divided into high dose group (H-TFRD), medium dose group (M-TFRD), low dose group (L-TFRD) and control group (control). The segmental bone defects were established with 12 rats in per group. The polymethyl methacrylate (PMMA) spacer was implanted into the femoral bone defect of rats in the first-stage surgery. About 4 weeks after first-stage surgery, induced membranes of 6 rats in each group were selected. The blood vessels and angiogenesis-related factors in the induced membrane were analyzed by hematoxylin-eosin (HE) and masson staining, western blot, qPCR and immunohistostaining. The remaining rats in per group underwent second-stage surgery (bone grafting). Twelve weeks after the bone grafting, the bone tissues was examined by X-ray, micro-computed tomography (Micro-CT), HE staining and enzyme-linked immunosorbent assay (ELISA) to evaluate the growth of the bone graft. Meanwhile, the TFRD-containing serum was collected from rats to culture osteoblasts in vitro. Cell Counting Kit-8 (CCK-8) method, Alizarin Red S (ARS) staining, western blot and immunofluorescence were used to detect effects of TFRD on the osteoblasts’ proliferation and BMP-SMAD signaling pathway. ResultsCompared with the L-TFRD and control groups, the number of blood vessels and the expression of angiogenesis-related factors (VEGF, TGF-β1, BMP-2, PDGF-BB and CD31) were higher in the H-TFRD and M-TFRD groups. The Lane-Sandhu X-ray score, bone mass and growth rate of the bone graft in the H-TFRD and M-TFRD groups were significantly better than those in the L-TFRD and control groups. In addition, medium and high doses of TFRD significantly increased the expression of BMP-SMAD pathway proteins (BMP-2, SMAD1, SMAD4, SMAD5 and RUNX2) in rat serum and bone graft. In vitro, after osteoblasts were intervened with TFRD-containing serum from the H-TFRD and M-TFRD groups, the cell viability, the number of mineralized nodules and the phosphorylation of BMP-SMAD pathway proteins were markedly increased. ConclusionTFRD could promote the formation of blood vessels and the expression of angiogenesis-related factors during the formation of the induced membrane. During the growing period of bone graft, it could facilitate the growth and mineralization of bone graft in a dose-dependent manner, which is partly related to the activation and phosphorylation of BMP-SMAD signaling pathway.

A bioactive synthetic membrane improves bone healing in a preclinical nonunion model

ObjectivesHigh energy long bone fractures with critical bone loss are at risk for nonunion without strategic intervention. We hypothesize that a synthetic membrane implanted at a single stage improves bone healing in a preclinical nonunion model. MethodsUsing standard laboratory techniques, microspheres encapsulating bone morphogenic protein-2 (BMP2) or platelet derived growth factor (PDGF) were designed and coupled to a type 1 collagen sheet. Critical femoral defects were created in rats and stabilized by locked retrograde intramedullary nailing. The negative control group had an empty defect. The induced membrane group (positive control) had a polymethylmethacrylate spacer inserted into the defect for four weeks and replaced with a bare polycaprolactone/beta-tricalcium phosphate (PCL/β-TCP) scaffold at a second stage. For the experimental groups, a bioactive synthetic membrane embedded with BMP2, PDGF or both enveloped a PCL/β-TCP scaffold was implanted in a single stage. Serial radiographs were taken at 1, 4, 8, and 12 weeks postoperatively from the definitive procedure and evaluated by two blinded observers using a previously described scoring system to judge union as primary outcome. ResultsAll experimental groups demonstrated better union than the negative control (p = 0.01). The groups with BMP2 incorporated into the membrane demonstrated higher average union scores than the other groups (p = 0.01). The induced membrane group performed similarly to the PDGF group. Complete union was only demonstrated in groups with BMP2-eluting membranes. ConclusionsA synthetic membrane comprised of type 1 collagen embedded with controlled release BMP2 improved union of critical bone defects in a preclinical nonunion model.

Treatment of Temporomandibular Joint Heterotopic Ossification: A Novel Protocol With Multimodal Therapy Based on Literature Review and Presentation of a Unique Case Report

The purpose of this study was to create a treatment protocol for cases of heterotopic ossification (HO) of the temporomandibular joint (TMJ), particularly those refractory to current TMJ HO protocols. In addition, we demonstrate the success of this protocol on a unique case of recurrent HO that failed multiple TMJ HO protocols in the setting of an improvised explosive device (IED) blast in a wounded warrior. An electronic literature review was conducted via PubMed and Web of Science. Twenty-five studies were identified to provide supporting evidence for a proposed, up-to-date protocol for the treatment of refractory TMJ HO. The authors present a case report of a wounded warrior with HO ankylosis of bilateral TMJs in the setting of IED blast and demonstrate successful use of our surgical and pharmacotherapeutic protocol. Based on the literature review, our proposed protocol consists of pharmacotherapy with celecoxib and etidronate, with weekly forced dilation (brisement) and home physical therapy with the TheraBite Jaw Motion Rehab System. Surgically, the TMJ should be treated with two-stage reconstruction using initial polymethyl methacrylate spacers and subsequent total joint replacement with custom prostheses, fat grafting, and 3-dimensional-navigated total resection of HO. This protocol was successfully utilized in our patient's refractory HO ankylosed TMJ secondary to IED blast, and the patient's maximal incisal opening was regained and has remained stable2years after surgery without recurrent HO. Our method for treatment in this case deviated from the standard TMJ Concepts HO protocol in that it included multimodal pharmacotherapy with celecoxib and etidronate. Based on our literature review and experience, we advise that clinicians utilize our protocol for the management of all craniofacial HO cases, particularly in cases of recurrent HO that fail conventional therapies and/or involving high-order blast trauma.