Treatment Of Infected Bone Defects Research Articles

A meta-analysis of the Masquelet technique and the Ilizarov bone transport method for the treatment of infected bone defects in the lower extremities.

Purpose:To compare the clinical outcomes of the Masquelet technique and Ilizarov bone transport method for the treatment of patients with infected bone defects in the lower extremities. Methods: Eligible studies were searched from six databases until 12 April 2021. Data extraction was independently conducted by two investigators, which was followed by a quality assessment. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to analyze continuous variables, while odds ratio (OR) and 95% CI were used to analyze categorical variables. All statistical analyses were conducted using RevMan 5.3 and Stata 12.0. Results: Thirteen articles were included in this meta-analysis. There was a significant difference observed in hospitalization costs (WMD [95% CI] = -1.75 [-2.50, -0.99] thousand US dollar, p < 0.00,001), final union time (WMD [95% CI] = -4.54 [-6.91, -2.17] months, p = 0.0002), time to full weight bearing (WMD [95% CI] = -1.73 [-3.36, -0.10] months, p = 0.04), quality of life (WMD [95% CI] = 7.70 [4.74, 10.67], p < 0.00,001), and the risk of complications (OR [95%CI] = 0.39 [0.19, 0.79], p = 0.009) between the Masquelet and Ilizarov groups. No significant differences in other outcomes were observed between the two groups. Conclusion: Masquelet technique exhibited the advantages in the lower hospitalization cost, shorter final union time, shorter time to full weight bearing, lower rate of complications, and better post-operative quality of life, compared with Ilizarov bone transport method. However, this finding should be confirmed in large-scale clinical samples.

An injectable gellan gum-based hydrogel that inhibits Staphylococcus aureus for infected bone defect repair.

The treatment of infected bone defects in complex anatomical structures, such as oral and maxillofacial structures, remains an intractable clinical challenge. Therefore, advanced biomaterials that have excellent anti-infection activity and allow convenient delivery are needed. We fabricated an innovative injectable gellan gum (GG)-based hydrogel loaded with nanohydroxyapatite particles and chlorhexidine (nHA/CHX). The hydrogel has a porous morphology, suitable swelling ratio, and good biocompatibility. It exerts strong antibacterial activity against Staphylococcus aureus growth and biofilm formation in vitro. We successfully established an infected calvarial defect rat model. Bacterial colony numbers were significantly lower in tissues surrounding the bone in rats of the GG/nHA/CHX group after debride surgery and hydrogel implantation in the defect regions than in rats of the blank group. Rats in the GG/nHA/CHX group exhibited significantly increased new bone formation compared to those in the blank group at 4 and 8 weeks. These findings indicate that gellan gum-based hydrogel with nHA/CHX can accelerate the repair of infected bone defects.

Facile fabrication of hollow mesoporous bioactive glass spheres: From structural behaviour to in vitro biology evaluation

Bone defects accompanied by infection or inflammation can significantly delay the healing process. To simultaneously achieve controlled release of local antibiotics for infection control and bone healing, bone-implantable delivery systems have been considered as a promising strategy. This study aims to improve drug loading capacity of bone-implantable delivery systems by introducing hollow structure mesoporous bioactive glass nanospheres (HMBGs) through a sol–gel process. Particularly, such core–shell bimodal-porous structured nanoparticles were prepared through a sacrificing template using cetyltrimethylammonium bromide (CTAB) as surfactant. It was found that varying the amount of CTAB during the synthesis process is a simple and effective approach for tuning the particle size, morphology, and structure of HMBGs. For in vitro drug release, HMBGs could sustain storage and release of vancomycin hydrochloride (VAN) via diffusion-controlled mechanism, thereby inhibiting the bacteria growth in the subsequent bacterial study. Moreover, HMBGs incorporated with VAN provided a biomimetic microenvironment favored by cell adhesion and proliferation. These findings support the compatibility of HMBG nanoparticles with antibiotics and their potential application in the treatment of infectious bone defects.

Multifunctional Modification of SIS Membrane with Chimeric Peptides to Promote Its Antibacterial, Osteogenic, and Healing‐Promoting Abilities for Applying to GBR

AbstractGuided bone regeneration (GBR) technology is the most widely used and stable method for bone defect repair. However, infectious bone defect limits the application of this technique. Herein, a small intestinal submucosa (SIS) membrane modified by chimeric peptides as a new type of GBR membrane is developed for efficacious tissue regeneration. Based on the main components of SIS membrane are I and III collagen, collagen binding peptides TKKTLRT and KELNLVY sequences are used to construct chimeric peptides with healing‐promoting peptide Hst1 or antibacterial osteogenic peptide JH8194, so as to realize the specifically target of SIS. This method achieves the fast and efficient multifunctional modification of SIS membrane. The chimeric peptides modified SIS (pSIS) membrane has satisfactory biocompatibility and a certain degree of antibacterial activity. Moreover, pSIS promotes the osteogenic related factors expression of rat bone mesenchymal stem cells and demonstrates great bone regeneration in rat skull defect model. Furthermore, pSIS accelerates the migration of oral epithelial cells in vitro and activate integrin α3β1 signal pathway contribute to wound healing. This study presents a novel biomaterial design of GBR membrane, specifically for the treatment of infectious bone defects.

Application of Graphene-Based Nanomaterials Combined with Early Exercise Rehabilitation Training in the Treatment of Patients with Infectious Bone Defects

Methods of treating bone defects include autogenous bone and allogeneic bone transplantation, tissue engineering technology, gene therapy, growth factor and adjuvant therapy of physical therapy, etc. However, most treatment schemes have obvious disadvantages. The purpose of this paper is to study the application of graphene-based nanomaterials combined with early exercise rehabilitation training in the treatment of patients with infectious bone defects. The biomedical properties and biomedical applications of graphene are briefly introduced through literature research and investigation, and bone defect diseases and commonly used treatment methods are analyzed. Graphene is used in many biomedical fields, such as disease diagnosis, biosensing, antibacterial and antiviral materials, cancer targeting, photothermal therapy, drug delivery, cell electrical stimulation, tissue engineering, stem cell technology, DNA sequencing and fluorescent (FL) tracking molecular probes. The effects of graphene-based nanomaterials and rehabilitation exercise on the treatment of infectious bone defects were compared through controlled experiments. The results show that although the repair effect of graphene-based nano-materials is not as good as that of autogenous bone, the difference is not significant, and it is better than calcium phosphate cement. After rehabilitation exercise, the curative effect of graphene experimental group was improved. In the 12th week, the tensile strength reached 5.78 N, and the torsional strength reached 0.93 N m, which exceeded the group of autogenous bone without rehabilitation exercise. This paper discusses the strength-related repair effect, but the in vivo toxicity of graphene needs further study.

Antibacterial calcium phosphate cement with human periodontal ligament stem cell‐microbeads to enhance bone regeneration and combat infection

Infectious bone defects remain a significant challenge in orthopedics and dentistry. Calcium phosphate cement (CPC) have attracted significant interest in use as local drug delivery system, which with great potential to control release of antibiotics for the treatment of infectious bone defects. Within the current study, a novel antibacterial scaffold of chitosan-reinforced calcium phosphate cement delivering doxycycline hyclate (CPCC + DOX) was developed. Furthermore, the capacity of CPCC + DOX scaffolds for bone regeneration was enhanced by the human periodontal ligament stem cells (hPDLSCs) encapsulated in alginate beads. CPCC + DOX scaffolds were fabricated to contain different concentrations of DOX. Flexural strength of CPCC + DOX ranged from 5.56 ± 0.70 to 6.2 ± 0.72 MPa, which exceeded the reported strength of cancellous bone. Scaffolds exhibited continual DOX release, reaching 80% at 21 days. Scaffold with 5 mg/ml DOX (CPCC + DOX5mg) had a strong antibacterial effect, with a 4-log colony forming unit reduction against S. aureus and P. gingivalis. The proliferation and osteogenic differentiation of hPDLSCs encapsulated in alginate hydrogel microbeads were investigated in culture with CPCC + DOX scaffolds. CPCC + DOX5mg had no negative effect on proliferation of hPDLSCs. Alkaline phosphatase activity, mineral synthesis, and osteogenic gene expressions for CPCC + DOX5mg group were much higher than control group. DOX did not compromise the osteogenic induction. In summary, the novel CPCC + DOX scaffold exhibited excellent mechanical properties and strong antibacterial activity, while supporting the proliferation and osteogenic differentiation of hPDLSCs. The CPCC + DOX + hPDLSCs construct is promising to enhance bone regeneration and combat bone infections in dental, craniofacial, and orthopedic applications.

The study of mechanical and drug release properties of the mineralized collagen/polylactic acid scaffold by tuning the crystalline structure of polylactic acid

Open bone fractures in clinical are not only difficult to heal but also at a high risk of infections. Annual cases of fractures which result from osteoporosis amount to approximately 9 million. The objective of this study is to load the antibiotic drug of vancomycin and tune its controlled delivery on a bone repair scaffold material of Mineralized Collagen/poly(lactic acid) (MCP) via changing the crystallinity of poly(lactic acid) to achieve inhibiting infection while repairing defects. We explored the crystallization process of the material during molding and prepared non-crystalline MCP1, MCP2, MCP3 and MCP4 by rapid freeze forming and crystalline MCP5 by tuning temperature decreasing rate. This method can control the micropore structure of the material; and the material changes from brittleness to toughness, which greatly enhances the control of mechanical properties. The drug release behavior of the material was studied for 28 days. Furthermore, the antibacterial property of the material was tested by the zone of inhibition, which shows the material good bacteriostasis. The controllable MCPs are expected to be substitutes for the treatment of infectious bone defects applying to clinical practical treatment.

A 3D printed Ga containing scaffold with both anti-infection and bone homeostasis-regulating properties for the treatment of infected bone defects.

Large bone defects face a high risk of infection, which can also lead to bone homeostasis disorders. This seriously hinders the bone healing process; therefore, the help of a dual-functional scaffold that has both anti-infection and bone-homeostasis-regulating capacities is needed in the treatment of infected bone defects. In this study, a 3D printed dual-functional scaffold composed of poly-ε-caprolactone (PCL), mesoporous bioactive glasses (MBG), and gallium (Ga) was produced. In vitro experiments demonstrated the excellent antibacterial ability of the PCL/MBG/Ga scaffold against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). The scaffold also significantly inhibited osteoclastic activity and promoted osteogenic differentiation. Furthermore, a rabbit model with an infected bone defect in the radius was used to evaluate the in vivo bone healing capability of PCL/MBG/Ga. The results demonstrate that the PCL/MBG/Ga scaffold can significantly accelerate bone healing and prevent bone resorption, suggesting its potential for application in repairing infected bone defects.

Carbon Nanomaterials in the Treatment of Infectious Bone Defects and Wound Scars after Wushu Fractures

Although modern antibiotics and surgical technology have made great progress, when using carbon nanomaterials to treat bone marrow-induced inflammation after martial arts fractures, how to simultaneously repair bone defects and control wound infections is the current focus of orthopedics research. This paper uses electrospinning technology to develop a carbon nanomaterial based on PLA, HA-g-PLA, and vancomycin. The surface morphology, biocompatibility, drug release, and osteogenesis of carbon nanomaterials are studied, selecting animal models to verify its effect in the treatment of osteomyelitis with bone defects and provide new ideas and new methods for the treatment of bone defects complicated by osteomyelitis infection. In this paper, carbon nanofibers containing doxycycline, a small molecule protease inhibitor, were prepared by simple blending. Encapsulation of carbon nanofibers can control the slow release of doxycycline and improve the effect of doxycycline in treating chronic wounds. This article uses two methods to prepare different types of osteomyelitis models and compare them. After injecting saline or bacterial solution, the two groups were sealed with bone wax and the incision was closed; the blank group did not do any treatment. Within 30 days after surgery, the appearance of the left hind limb wound and general signs of infection were closely monitored, body temperature was measured, and blood was collected from the ear veins of experimental animals to analyze the changes in C-reactive protein (CRP) and procalcitonin levels (PCT); X-ray, CT imaging, and histological observation were performed on 14 and 28 days. Studies have shown that when the drug loading of doxycycline increases from 10% to 15%, this is related to the change in properties of the polylactic acid fiber membrane from hydrophobic to hydrophilic caused by the increase in doxycycline drug loading.

Treatment options for infected bone defects in the lower extremities: free vascularized fibular graft or Ilizarov bone transport?

ObjectiveThe objective was to explore the relative indications of free vascularized fibular graft (FVFG) and Ilizarov bone transport (IBT) in the treatment of infected bone defects of lower extremities via comparative analysis on the clinical characteristics and efficacies.MethodsThe clinical data of 66 cases with post-traumatic infected bone defects of the lower extremities who underwent FVFG (n = 23) or IBT (n = 43) from July 2014 to June 2018 were retrieved and retrospectively analyzed. Clinical characteristics, operation time, and intraoperative blood loss were statistically compared between two groups. Specifically, the clinical efficacies of two methods were statistically evaluated according to the external fixation time/index, recurrence rate of deep infection, incidence of complications, the times of reoperation, and final functional score of the affected extremities.ResultsGender, age, cause of injury, Gustilo grade of initial injury, proportion of complicated injuries in other parts of the affected extremities, and numbers of femoral/tibial defect cases did not differ significantly between treatment groups, while infection site distribution after debridement (shaft/metaphysis) differed moderately, with metaphysis infection little more frequent in the FVFG group (P = 0.068). Femoral/tibial defect length was longer in the FVFG group (9.96 ± 2.27 vs. 8.74 ± 2.52 cm, P = 0.014). More patients in the FVFG group presented with moderate or complex wounds with soft-tissue defects. FVFG treatment required a longer surgical time (6.60 ± 1.34 vs. 3.12 ± 0.99 h) and resulted in greater intraoperative blood loss (873.91 ± 183.94 vs. 386.08 ± 131.98 ml; both P < 0.05) than the IBT group, while average follow-up time, recurrence rate of postoperative osteomyelitis, degree of bony union, and final functional scores did not differ between treatment groups. However, FVFG required a shorter external fixation time (7.04 ± 1.72 vs. 13.16 ± 2.92 months), yielded a lower external fixation index (0.73 ± 0.28 vs. 1.55 ± 0.28), and resulted in a lower incidence of postoperative complications (0.87 ± 0.76 vs. 2.21±1.78, times/case, P < 0.05). The times of reoperation in the two groups did not differ (0.78 ± 0.60 vs. 0.98 ± 0.99 times/case, P = 0.615).ConclusionBoth FVFG and IBT are effective methods for repairing and reconstructing infected bone defects of the lower extremities, with unique advantages and limitations. Generally, FVFG is recommended for patients with soft tissue defects, bone defects adjacent to joints, large bone defects (particularly monocortical defects), and those who can tolerate microsurgery.

Novel ternary vancomycin/strontium doped hydroxyapatite/graphene oxide bioactive composite coatings electrodeposited on titanium substrate for orthopedic applications

Currently, the clinical application of hydroxyapatite (HA) coatings are limited due to the lack of anti-infection, osteoinductivity and poor mechanical properties. In the present study, the strontium-containing hydroxyapatite (SrHA)/graphene oxide (GO)/vancomycin (Va) nanocomposite coating with drug delivery and antibacterial activity was fabricated by electrochemical deposition (ECD) on titanium substrate. The results showed that by inducing a large number of crystal nucleation points, the oxygen-containing groups on the two-dimensional surface of GO induced the formation of extremely fine SrHA/Va/GO composite coatings. Furthermore, the functional coating exhibited a moderately nanostructured surface with average values of roughness and contact angle of 31.9° and 126 nm, respectively, which provided a suitable contact surface for osteoblast proliferation and differentiation. Moreover, compared with HA coatings without GO, the hardness and elastic modulus of SrHA/Va/GO composite coatings were enhanced by 67.6 % and 121 %, respectively. The release process of Va from the SrHA/Va/GO coating showed a phased release law, which broke out within the first 5 h and then slowly and controlledly released within 14 h, which is due to the physical and chemical adsorption of Va. The inhibition zone and colony count experiments showed that the SrHA/Va/GO coating revealed satisfactory inhibitory effects on S. aureus and S. epidermidis, and the inhibition could last for 3 days. Compared with pure titanium, SrHA/Va/GO composite coating can significantly promote the adhesion, proliferation and differentiation of MC3T3-E1 cells. In conclusion, SrHA/Va/GO exhibited good mechanical properties, excellent osteoinductivity and antibacterial properties, confirming its potential as a new surface modification material for the prevention and treatment of infectious bone defects.

An antibiotic cement-coated locking plate as a temporary fixation for treatment of infected bone defects: a new method of stabilization

BackgroundThe induced membrane technique has achieved good clinical results in the treatment of infected bone defects, and external fixation is the main method, but it causes inconvenience and complications in patients. In this study, our objective was to investigate the outcomes of using an antibiotic cement-coated locking plate as a temporary internal fixation in the first stage of the surgical induced membrane technique for treating extremities with infected bone defects.MethodsWe retrospectively analysed patients with lower extremity infected bone defects in our department between January 2013 and December 2017. All patients were treated with the induced membrane technique. In the first stage, the defects were stabilized with an antibiotic cement-coated locking plate as a temporary fixation after debridement, and polymethyl methacrylate cement was implanted to induce the formation of a membrane. In the second stage, bone grafting rebuilt the bone defects after infection control, and the temporary fixation was changed to a stronger fixation.ResultsA total of 183 patients were enrolled, with an average follow-up duration of 32.0 (12–66) months. There were 154 males and 29 females with an average age of 42.8 (10–68) years. The infection sites included 81 femurs, 100 tibias and 2 fibulas. After the first stage of treatment (infection control), 16 (8.7%) patients had recurrence of infection. In terms of the incidence of complications, 4 patients had poor wound healing, 2 patients had fixation failure and 1 patient had femoral fracture due to a fall. After the second stage of treatment (bone reconstruction), there were 24 (13.1%) recurrences of infection, with a mean time of 9.9 months (range 0.5 to 36). Among them, 18 patients underwent bone grafting after re-debridement, 6 received permanent placement of antibiotic bone cement after debridement and 2 patients refused further treatment and chose amputation. Bone healing was achieved in 175 (95.9%) patients at the last follow-up, and the average time to bone union was 5.4 (4–12) months.ConclusionsAntibiotic cement-coated locking plates have good clinical effects in the control of bone infection, but attention must be paid to the possible difficulty of skin coverage when applied in calves.

Potent bioactive bone cements impregnated with polystyrene-g-soybean oil-AgNPs for advanced bone tissue applications

ABSTRACTPostoperative infection in orthopaedic and trauma surgery is one of the most feared complications. Recently, the high prevalence of multidrug-resistant bacteria has made the antibiotic treatment ineffective; thus novel non-antibiotic alternative approaches to this problem are urgently needed. Based on these expectations, in this work, in order to enhance the cytocompatibility and antibacterial performances of poly (methyl methacrylate (PMMA) and beta-tricalcium phosphate (β-TCP) bone cements were impregnated with polystyrene (PS)-g-soybean oil graft copolymer containing AgNPs (PS-Agsbox), and we assessed the antimicrobial activity of the fabricated bone cements against Staphylococcus aureus and Escherichia coli. Nanoparticles at concentration of 1.25% (5 β-TCP) w/w in β-TCP bone cements were able to inhibit pathogens growth, while a concentration of 3.75% (15PMMA) was needed for PMMA bone cement. Therefore, the impregnated bone cements with PS-AgsboxNPs may be further explored as an alternative antimicrobial therapy for the treatment of infected bone defects.

Induced-Membrane Technique in the Management of Posttraumatic Bone Defects.

Critical-size bone defects are defined as bone defects where spontaneous regeneration is not expected without treatment1. The characteristics of bone defects (etiology, location, size, presence of infection, and soft-tissue conditions) vary greatly and, to be effective, the treatment method should address this variability. The induced-membrane technique, or Masquelet technique, is a method for treating critical-size bone defects2,3 of various sizes and anatomic locations. It has been used to treat infected and noninfected bone defects and may be performed with a variety of fixation methods2,3. The induced-membrane technique is a 2-stage procedure. The first stage consists of debridement followed by insertion of a polymethylmethacrylate (PMMA) spacer in the bone defect. The presence of the PMMA leads to a foreign-body reaction with the development of a thick pseudosynovial membrane that is extremely vascularized and rich in growth factors. The filling of the bone defect with the cement spacer prevents fibrous tissue invasion and allows the development of an optimal vascularized gap for bone-grafting. After 6 to 8 weeks, the membrane around the spacer is carefully opened for the removal of the spacer, which is then replaced by bone graft2,3, which can be expanded with allograft or biomaterials. Alternatives include vascularized or nonvascularized autologous bone graft, allograft, bone transport methods, titanium cages, megaprostheses, shortening, and amputation. Posttraumatic bone defects frequently are associated with soft-tissue injury and infection that impair the local vascularization and the healing potential. The highly vascularized induced membrane may play a role in restoring the local regenerative capacity. Numerous studies have demonstrated its successful use in the treatment of posttraumatic bone defects in the hand, forearm, humerus, femur, tibia, and foot. The induced-membrane technique is especially advantageous in the treatment of infected bone defects because the presence of the spacer helps in the treatment of the infection by reducing dead space, acting as a local antibiotic carrier, and promoting some degree of bone stability3-5.

Clinical application of local antibiotic carriers in infected bone defects

Early management of open extremity fractures and treatment of chronic osteomyelitis, in general, require thorough debridement. Radical debridement of the contaminated or infected bone tissues usually results in bone defects. If such bone defects are not dealt with properly, they can easily deteriorate into infected ones. Treatment of infected bone defects can be extremely complicated. Application of local antibiotic delivery system can simultaneously fill the bone defects, prevent and treat the infection by delivering a high concentration of antibiotics to the lesion. The clinical antibiotic carriers can be divided roughly into 2 types: non-biodegradable and biodegradable. The biodegradable type involves bioceramic, natural polymer, synthetic polymer and composite materials. This literature review summaries the characteristics and clinical applications of current local antibiotic carriers. Key words: Osteomyelitis; Fractures, open; Calcium sulfate; Bone defects; Polymethyl methacrylate

Regenerating infected bone defects with osteocompatible microspheres possessing antibacterial activity.

Treatment of infected bone defects still remains a formidable clinical challenge, and the design of bone implants with both anti-bacterial activity and -osteogenesis effects is nowadays regarded as a powerful strategy for infection control and bone healing. In the present study, bioresorbable porous-structured microspheres were fabricated from an amphiphilic block copolymer composed of poly(l-lactide) and poly(ethyl glycol) blocks. After being surface coated with mussel-inspired polydopamine, the microspheres were loaded with nanosilver via the reduction of silver nitrate and apatite via biomineralization in sequence. At optimized loading amounts, the nanosilver-loaded microspheres showed no unfavorable effects on the proliferation and differentiation of bone marrow mesenchymal stem cells despite preserving strong antibacterial activity in in vitro evaluations. For the critical-sized defects (φ = 8 mm) in the rat cranium that was pre-infected with Staphylococcus aureus, the filling of the dual-purpose microspheres demonstrated an effective way to kill bacteria in vivo, and in the meantime, it promoted new bone formation efficiently alongside the degradation of microspheres. Thus, the results suggested that bioresorbable microspheres with both osteoconductive and antibacterial activities were a good choice for treating infected bone defects.

Clinical research of Ilizarov technique for treatment of lower limb infected bone defect

Objective To explore the clinical efficacy of Ilizarov technique for infected-bone defect in lower extremity. Methods From January 2013 to December 2016, data of 31 consecutive patients with lower limb infected bone defect were retro-spectively analyzed. There were 23 males and 8 females, with an average age of 35.8 years (range, 5-57 years). 16 cases of infect-ed bone defect were on femur while the other 15 were on tibia. The infected bone defects were developed from blood-borne osteo-myelitis in 3 cases, from open fracture (according to Gustlio classification, Gustilo Ⅱ 8, Ⅲa 5, Ⅲb 4) surgery in 17 cases (12 cas-es after external fixation and 5 cases after internal fixation), and from closed fracture surgery of plate or intramedullary nail fixation in 11 cases. Soft-tissue defects were observed in 5 cases, including 1 femur and 4 tibia. The previous operations were performed with an average operation time of 3.2 (range, 2-5 times) and treatment duration of 9.6 months (range, 3-21 months). The operation process was one stage debridement, external fixation, combined with bone osteotomy and transportation. Bone transportation start-ed 7 to 10 days after osteotomy with a speed of 1 mm/d, and 0.25 mm/time. Healing rate and complications were recorded during the follow-up period and were assessed by Paley fracture healing score. Results The length of bone defect after debridement was 6.9 cm (range, 3-13.5 cm). There were 27 cases positive in bacterial culture, who were treated by sensitive antibiotics. The other 4 cases were negative and treated by broad-spectrum antibiotics. The bone lengthening speed was 0.76 mm/d (range, 0.56-0.86 mm/d). All bone and soft-tissue defects healed, with average bone healing time of 11.5 months (range, 6-18.5 months). All patients were followed-up for 12 to 48 months (average, 25.5 months). Pin infection appeared in 11 cases (8 cases on femur and 3 cases on tibia) who were cured by oral antibiotics, serial dressing and debridement. Axial displacement was presented in 4 cases on femur and were corrected by external fixation adjustment. No recurrent infection was observed and the limb length restored normal. Postoper-ative complications in femur were 106.3% (17/16) comparing 46.7% (7/15) in tibia. According to Paley fracture healing score, 12 cases were excellent, 14 were good and 5 were fair, yielding an excellent to good rate of 83.9% (26/31). Conclusion Ilizarov tech-nique is an effective way in the treatment of infected-bone defects. The complication rates on femur observed in this study were slightly higher than that on tibia. Key words: Ilizarov technique; Femur; Tibia; Infection

Drug and ion releasing tetracalcium phosphate based dual action cement for regenerative treatment of infected bone defects

Calcium phosphate cements (CPCs) are ideally suited for the local delivery of antibiotics in infected bone defects as they have multiple binding sites for loading various drugs. CPCs can also be substituted with ions such as Ag+, Zn2+, Mg2+, Sr2+, etc., to exhibit extended broad-spectrum antimicrobial activity. Strontium (Sr) in particular is known to enhance the new bone formation and decrease bone resorption. The current work aims to develop a dual action tetracalcium phosphate (TTCP) based cement which releases both the Sr2+ ion and ornidazole antibiotic drug for the treatment of bone infections. The TTCP with Sr2+ ion substitution was prepared by the solid state reaction method and it was used to form ornidazole loaded CPC. The ornidazole loaded cement prepared using 8 at% Sr substituted TTCP (8SCPC-O) showed complete hydroxyapatite (HA) formation in phosphate buffered solution at the end of 1 week. Fine needle-shaped HA crystals were observed in 8SCPC-O cement. In vitro drug release studies showed an accelerated ornidazole release from the 8SCPC-O sample when compared to samples without Sr substitution. Ornidazole releasing cements were found to be biocompatible with skeletal myoblast (L6) cells. Antibacterial activity of ornidazole releasing cement was evident from day 1 onwards against E. coli. The above results suggest 8SCPC-O as a good candidate for treating local bone infections.

Vancomycin-impregnated electrospun polycaprolactone (PCL) membrane for the treatment of infected bone defects: An animal study.

There is no consensus for the management of critical infected bone defects. The purpose of this study was to produce a vancomycin-impregnated electrospun polycaprolactone (PCL) membrane for the treatment of infected critical bone defects, and test it in a rabbit model. Electrospinning produced a resorbable PCL fiber membrane containing vancomycin approximately 1 mm in thickness, with a pore diameter of <10 μm. Femur defects were made in the limbs of 18 rabbits and infected with Staphylococcus aureus. The rabbits were divided into three groups according to treatment: (1) Experimental group: rabbit freeze-dried allogeneic bone graft and the vancomycin-PCL membrane. (2) Control group 1: bone graft. (3) Control group 2: vancomycin-PCL membrane only. Culture showed no difference in osteoclast activity between the three groups. Transwell testing showed that almost no fibroblasts passed through the membrane during the first 24 h, but some fibroblasts were able to pass it after 72 h. At 12 weeks after surgery, there was significantly less inflammatory cell infiltration in the experimental compared to the control groups. New bone formation and fracture bone callus were greater in the experimental group than control groups. We thus conclude the resorbable electrospun vancomycin-impregnated PCL membrane was effective at controlling bone infection, and in the regeneration of bone in a critical bone defect animal model.

Xenogenic bone with chitosan/norvancomycin sustained-release system for treatment of infectious bone defects in rabbits

Objective To investigate the effects of xenogenic bone with chitosan/norvancomycin sustained-release biomaterials in treating infectious bone defects in rabbits. Methods Xenogenic bone with chitosan/norvancomycin sustained-release biomaterials was made by electrospinning technique. Rabbit infectious bone defect models were made by Methicillin-resistant Staphylococcus aureus. A successful model was evaluated with the standard of more than three points in Norden score assessment. All models were divided into two groups by random number table method, with eight models in each. The control group was treated with surgical debridement, and the experimental group was implanted with bone particles of xenogenic bone with chitosan/norvancomycin sustained-release system after debridement. Postoperatively, general conditions, X-ray, histological results of HE staining, and bacteriological examination results of the rabbits were observed. Results X-ray showed significant bone defects, sequestration, periosteal reaction, and soft tissue swelling after one month of modeling, with Norden score of (3.84±0.52)points. The general conditions were good and the sinus tracts were healed in experimental group after two months of treatment. The control group demonstrated generally poor conditions with swollen sinus and purulent discharge. Two rabbits were died of sepsis. The pathological scores of tibial were (0.41±0.08)points in experimental group, and (3.27±0.26)points in control group by gross observation. The pathological score of experimental group was significantly lower than control group(P<0.05). The bone defects were basically repaired in experimental group. The longest diameter of bone defect in experimental group was (0.11±0.02)cm, significantly smaller than (0.48±0.06)cm in control group (P<0.05). There were no obvious signs of osteomyelitis and the bone defects were well repaired in experimental group. Periosteal reaction, soft tissue swelling, a substantial number of bone destruction, and sequestration were observed in control group. The Norden score was (1.32±0.23)points in experimental group, lower than (5.21±0.48)points in control group(P<0.05). HE staining showed a large amount of trabecular bone formation, bone cell formation, and fibrous hyperplasia in experimental group, with no obvious signs of infection. On the other hand, infiltration of inflammatory cells, necrotic tissue, and sequestration were observed in control group. The histological score was(0.61±0.10) points in experimental group, lower than (4.21±0.41) points in control group (P<0.05). The negative rate of bacterial culture in experimental group was 33%, lower than 100% in control group (P<0.05). Conclusion Xenogenic bone with chitosan/norvancomycin sustained-release biomaterials has excellent effect in infection clearance and bone defect reparation in treatment of infectious bone defects in rabbits. Key words: Osteomyelitis; Chitosan; Anti-bacterial agents; Drug delivery systems