Aims

There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN).

Aim. There are no definitive criteria for the definition of osteomyelitis in the hand and wrist and published case series are small. It remains a relatively uncommon, but difficult to treat problem. We present a series of 30 cases from 2016 to 2021 from a tertiary referral centre. We propose that the principles of thorough surgical debridement, dead space management, skeletal stabilisation and culture driven antibiotic therapy are the key to management of osteomyelitis in the hand and wrist. In addition, we show how these basic principles can be used for both functional and aesthetic impact for the wrist and digits with illustrated cases. Methods. We conducted a retrospective chart review over a 6 year period and recorded the site of the infection, the soft tissue and bony management, whether antibiotic eluting bone filler was used, the isolated bacterial species, the number of surgical procedures undertaken to treat the infection and the success rate for clearing the infection. Results. 17/30 cases had pre-existing metalwork in-situ. There were 19 phalangeal/metacarpal infections and 11 carpal infections. 24 patients had native joint involvement. A drug eluting bone void filler was used in 23/30 cases in order to manage the dead space. In 7/30 cases had polymicrobial organisms isolated, 15/30 had only one organism cultured. The most common organism cultured was Staphylococcus aureus. Complete resolution of osteomyelitis or joint infection was achieved in 29/30 cases with follow up ranging from six months to six years. 2/30 cases required thorough debridement of the distal phalanx; bone void filler provided an aesthetically optimal result to improve fingertip contour whilst managing the dead space. Conclusion. Osteomyelitis of the hand and wrist is optimally managed with thorough surgical debridement, dead space management with a drug eluting bone void filler, skeletal stabilisation and culture directed antibiotic therapy. In addition, the bone void filler provides pulp support and improves the aesthetic contour of fingertips in which distal phalangeal osteomyelitis was successfully treated

Introduction

Cerament, a bioresorbable hydroxyapatite and calcium sulfate cement, is known to be used as a bone-graft substitute in traumatic bone defect cases. However, its use in open fractures has not previously been studied.

Aims

Treatment of chronic osteomyelitis (COM) for young patients remains a challenge. Large bone deficiencies secondary to COM can be treated using induced membrane technique (IMT). However, it is unclear which type of bone graft is optimal. The goal of the study was to determine the clinical effectiveness of bone marrow concentrator modified allograft (BMCA) versus bone marrow aspirate mixed allograft (BMAA) for children with COM of long bones.

Aims

CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model.

Purpose. Infections in orthopaedic surgery are costly, debilitating complications. The search for new treatments and prevention strategies has led to the use of antibiotic-filled calcium sulfate (CaS) as a bone void filler that is both safe and effective. The purpose of this study was to examine the available data on the efficacy of this technology. Methods. A literature search was performed for studies that evaluated the use of antibiotic-loaded CaS cement in orthopaedics published between inception of the databases to 2017. Selected studies included randomized controlled trials (RCTs) and observational studies published in the English language that met the following criteria: 1) patients underwent an orthopaedic procedure; 2) CaS cement with an antibiotic was used; and 3) at least one of our outcomes were mentioned. Outcomes included resolution of infection, complications related to treatment, subsequent surgeries, overall infection rate, fracture union rate, clinical outcomes, and wound complications. A total of 17 studies were included. Results. Ten studies examined the use of antibiotic-eluting CaS cement with surgical debridement to treat osteomyelitis and reported resolution rates ranging from 80–100%. Two studies examined CaS for prophylaxis of infection after open fracture, with subsequent infection rates ranging from 0–22%. Two studies examined infected non-unions with CaS used as an adjunct to surgery with an 87.5% infection clearance rate. Finally, three studies examined the use of local antibiotic release from CaS in the repair of infected TKAs or THAs, with success rates ranging from 52–93.3%. Conclusion. Initial results support the use of CaS with surgical debridement for osteomyelitis and infected non-unions. Results are mixed for CaS use in the prophylaxis of infection after open fractures and for PJIs, thereby necessitating further research. Overall the studies were small, retrospective, and lacked controls. Further research should focus on RCTs to minimize bias and investigate for non-inferiority. For any figures or tables, please contact authors directly

Aim. To study the antimicrobial effect of a gentamicin loaded bio-composite bone void filler in relation to a limited or extensive debridement of osteomyelitis lesions, respectively. Methods. Nine pigs were inoculated into the right proximal tibial bone with a high virulent gentamicin sensitive strain of Staphylococcus aureus (10. 4. CFU). Seven days after inoculation, Group A pigs (n=3) were exposed to a limited debridement of the bone lesion, whereas Group B pigs (n=3) were exposed to an extensive debridement. The bone defects of Groups A and B were filled with (2–5 ml) of an absorbable gentamicin (175 mg/10 mL) loaded bio-composite. The animals of Group A and B were euthanized 12 days after revision surgery. Group C animals did not undergo revision surgery and were euthanized seven (n=1) or nineteen (n=2) days post inoculation in order to follow the development of the untreated infection. None of the animals were treated with systemic antimicrobials. All bones were exposed to a post mortem CT scan and rigours pathological examinations. The surrounding bone tissue and the bio-composite were sampled for microbiology. Results. All animals developed a substantial purulent bone infection in the inoculated leg prior to revision surgery. In the cases of limited debridement, the bone lesions surrounding the bio-composite bone void filler had clearly expanded since revision surgery, and contained extensive amounts of pus, necrotic bone tissue and oedematous fibrotic tissue. In the cases of extensive debridement, the bio-composite bone void filler was surrounded by only a few mm of fibrosis and sclerotic bone tissue i.e. the bone lesions were not expanding. However, in one pig the bio-composite bone void filler was communicating with a small purulent osteolytic lesion without a sclerotic border indicating appearance after revision surgery. In all pigs, S. aureus bacteria were post mortem cultured from the adjacent bone tissue and the bio-composite surface. Conclusions. The gentamicin concentrations within the bio-composite could not eradicate the residual infection after debridement. However, extensive debridement and filling of the bone void with gentamicin loaded bio-composite contained the lesion formed by revision surgery, which are important complementing roles as adjuvant to systemic antimicrobial therapy and the immune system in eradication of the infection. The present study emphasizes that extensive debridement is fundamental for successful treatment of bone infections and that antimicrobial loaded bone void fillers or bone substitutes should not be used as an alternative to extensive debridement

Aims

Custom flange acetabular components (CFACs) are a patient-specific option for addressing large acetabular defects at revision total hip arthroplasty (THA), but patient and implant characteristics that affect survivorship remain unknown. This study aimed to identify patient and design factors related to survivorship.

Objectives. Bone void fillers are increasingly being used for dead space management in arthroplasty revision surgery. The aim of this study was to investigate the influence of calcium sulphate bone void filler (CS-BVF) on the damage and wear of total knee arthroplasty using experimental wear simulation. Methods. A total of 18 fixed-bearing U2 total knee arthroplasty system implants (United Orthopedic Corp., Hsinchu, Taiwan) were used. Implants challenged with CS-BVF were compared with new implants (negative controls) and those intentionally scratched with a diamond stylus (positive controls) representative of severe surface damage (n = 6 for each experimental group). Three million cycles (MC) of experimental simulation were carried out to simulate a walking gait cycle. Wear of the ultra-high-molecular-weight polyethylene (UHMWPE) tibial inserts was measured gravimetrically, and damage to articulating surfaces was assessed using profilometry. Results. There was no significant difference (p  >  0.05) between the wear rate of implants challenged with CS-BVF (3.3 mm. 3. /MC (95% confidence interval (CI) 1.8 to 4.8)) and the wear rate of those not challenged (2.8 mm. 3. /MC (95% CI 1.3 to 4.3)). However, scratching the cobalt-chrome (CoCr) significantly (p < 0.001) increased the wear rate (20.6 mm. 3. /MC (95% CI 15.5 to 25.7)). The mean surface roughness of implants challenged with CS-BVF was equivalent to negative controls both after damage simulation (p = 0.98) and at the conclusion of the study (p = 0.28). Conclusion. When used close to articulating surfaces, a low-hardness, high-purity CS-BVF had no influence on wear. When trapped between the articulating surfaces of a total knee arthroplasty, CS-BVF did not scratch the surface of CoCr femoral components, nor did it increase the wear of UHMWPE tibial inserts compared with undamaged negative controls. Cite this article: R. M. Cowie, S. S. Aiken, J. J. Cooper, L. M. Jennings. The influence of a calcium sulphate bone void filler on the third-body damage and polyethylene wear of total knee arthroplasty. Bone Joint Res 2019;8:65–72. DOI: 10.1302/2046-3758.82.BJR-2018-0146.R1

Aim. Antibiotic-loaded biomaterials are often used in dead space management after excision of infected bone. This study assessed the chronological progression of new bone formation in infected defects, filled only with an absorbable, osteoconductive bone void filler with Gentamicin (1). Method. 163 patients were treated for osteomyelitis or infected fractures with a single-stage excision, implantation of antibiotic carrier, stabilisation and wound closure. All had Cierny & Mader Type III (n=128) or Type IV (n=35) infection. No bone grafting was performed in any patient. Patients were followed up for a minimum of 12 months (mean 21.4 months; 12–56). Bone void filling was assessed on serial digitised, standardized radiographs taken immediately after surgery, at 6 weeks, 3, 6 and 12 months and then yearly. Data on defect size, location, degree of void filling, quality of the bone-biomaterial interface and material leakage were collected. Bone formation was calculated at final follow-up, as a percentage of initial defect volume, by determining the bone area on AP and lateral radiographs to the nearest 5%. Results. 138 patients had adequate radiographs for assessment. Infection was eradicated in 95.7%. 2.5% of patients suffered a fracture during follow-up. Overall, bone formation was good (mean 73.8% defect filling), with one quarter of patients having complete defect filling and 87% having more than 50% of the defect healed. Bone formed better in metaphyseal defects compared to diaphyseal defects (mean 79% filling vs 66%; p<0.02). Good interdigitation of the biomaterial with the host bone, seen on the initial radiograph, was associated with more bone formation (77% vs 69%; p=0.021). Leakage of the biomaterial out of the defect reduced mean bone formation from 77% to 62% (p=0.006). 38 cases had radiographs more than 2 years after implantation. In 24 (63.2%), bone formation continued to increase after the first year radiograph. Conclusion. This biomaterial was effective in allowing significant amounts of bone to form in the defect. This removed the need for bone grafting in this series, with a low risk of fracture or recurrent infection. However, bone formation is affected by the site of the lesion and the adequacy of filling at surgery. It is important to achieve good contact between the bone surface and the biomaterial at operation. Bone formation is slow and progresses for at least 2 years after implantation, in two thirds of patients

Aims

Local antibiotics are used in the surgical management of foot infection in diabetic patients. This systematic review analyzes the available evidence of the use of local antibiotic delivery systems as an adjunct to surgery.

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.

Aims

Calcium sulphate has traditionally been used as a filler of dead space arising during surgery. Various complications have been described following the use of Stimulan bio-absorbable calcium sulphate beads. This study is a prospective observational study to assess the safety profile of these beads when used in revision arthroplasty, comparing the complication rates with those reported in the literature.

Objectives

The aim of this systematic literature review was to assess the clinical level of evidence of commercially available demineralised bone matrix (DBM) products for their use in trauma and orthopaedic related surgery.

Introduction. Calcium sulfate bone void fillers (CS-BVF) are increasingly being used for dead space management in infected arthroplasty revision surgery. The use of loose beads of CS-BVF close to the articulating surfaces of an implant means there is potential for them to migrate between the articulating surfaces acting as a third body particle. The aim of this study was to investigate the influence of CS-BVF on the third body wear of total knee replacements. Methods. The influence of CS-BVF on wear was investigated using the commercially available CS-BVF ‘Stimulan’ (Biocomposites Ltd., UK) and posterior stabilised U2 total knee replacement system implants (United Orthopaedic Corp., Taiwan). The experimental wear simulation was performed using a six station ProSim electropneumatic knee simulator (Simulation Solutions, UK) running the Leeds intermediate kinematics input profile [1]. To investigate the damage that could be caused by the third body particles, 5cc of CS-BVF beads (excess) were placed on the tibial component of the implant, the simulator was run dry for 60 cycles before adding lubricant (25% bovine serum supplemented with 0.03% sodium azide) and running for an additional 115,000 cycles representative of the 6–8 weeks the CS-BVF are present in the body prior to their resorption. The surface topography of the cobalt chrome femorals was analysed using contacting profilometry to ascertain whether the third body particles of CS-BVF had damaged the surfaces. To investigate the influence of CS-BVF on the third body wear of the UHMWPE tibials, 3 million cycles (MC) of wear simulation was subsequently carried out. The wear of the UHMWPE tibials was assessed gravimetrically and the wear of implants tested with CS-BVF was compared to the wear against negative controls (initial Ra∼0.02µm) and positive controls (initial Ra ∼0.4µm) damaged with a diamond stylus. N=6 was completed for each condition, statistical analysis was carried out using ANOVA with significance taken at p<0.05. Results. Light scratching was visible on the surface of the cobalt chrome femorals after the implants were challenged with the CS-BVF, however, there was no significant difference (p>0.05) between the surface roughness of the negative controls and those challenged with CS-BVF for any of the roughness parameters of interest (Table 1 & Figure 1). 3MC of wear simulation showed no significant difference (p>0.05) between implants subjected to the third body wear protocol and the negative controls (Figure 2). To significantly increase the wear of the UHMWPE tibials, the damage to the cobalt chrome femorals had to be above a threshold as in the positive controls scratched with a diamond stylus. Conclusions. This study showed that the CS-BVF ‘Stimulan’ had no influence on the third body wear or surface topography of total knee replacements compared to negative controls. Therefore, when used close to articulating surfaces of a metal-on-polyethylene joint replacement, CS-BVF may not influence the wear of an implant or be detrimental to its longevity

Calcium phosphate cements (CPC) are used as biocompatible and bioactive bone void fillers. Ideally, the mechanical properties of these cements should match those of the surrounding bone. The knowledge of the real mechanical properties of the material is important in the decision-making process regarding possible use of the CPCs in different anatomical sites. Although it is generally recognized that these cements are stiffer and more brittle than desired, there is a limited amount of data about the possible deformation of this class of material before failure. The focus of this study was to determine these properties of injectable CPCs. Two different types of self-setting CPCs were investigated in this study: i) hydroxyapatite (HA), that historically has been the most widely studied CPC; ii) brushite, that recently has attracted attention due to its faster resorption than that of HA in vivo. Specimens of both cement types were prepared by mixing a powder phase with a liquid phase that were left to harden in phosphate buffered saline at 37°C. Once set, the specimens underwent a quasi-static compressive test to determine the compressive strength, the elastic modulus and the maximum deformation of the two materials. The material testing machine was equipped with a digital image correlation system, which allows accurate measurement of material deformation directly on the specimen surface. Brushite was found to be significantly more stiff (+80%) and resistant (+84%) than HA. Similar findings were found for the energy needed to create a first crack on the specimen surface. However, the first crack appeared on the specimen surface at the same low deformation level (∼0.15%) independently of the type of material tested. Complete failure of both materials occurred, on average, before reaching 0.25%. It has been demonstrated that the compressive behaviour of CPCs depends on their composition and porosity [1]. One of the main reasons for the high strength and stiffness of the brushite studied here was its low porosity (∼12%). However, the maximum deformation is not positively affected by this decrease in porosity. In fact, both materials show the same brittle behaviour, i.e. they undergo comparably little deformation before they break. Under these conditions, increasing the compressive strength may not always be beneficial clinically, e.g. in the treatment of vertebral compression fractures, where the high stiffness of the bone cements used has been identified as a risk factor for adjacent-level fractures [2]. However, it is not clear whether a 20-fold higher stiffness than the trabecular bone would give a different clinical outcome than a 10-fold higher stiffness. These high-strength, high-stiffness cements may also be used as a basis for further biomaterial development, e.g. in the creation of macro-porous scaffolds, which is usually challenging due to the commonly low mechanical properties of the base CPC material

Objectives

Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing.

The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets.

DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory.

Aims. Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection. Materials and Methods. Antibiotic was loaded into a graft and subsequently evaluated for drug elution kinetics and the inhibition of bacterial growth. A rat femoral condylar plug model was used to determine the effect of the graft, loaded with antibiotic, on bone healing. Results. We found that tobramycin loaded into a graft composed of bioglass and DBM eluted antibiotic above the minimum inhibitory concentration for three days in vitro. It was also found that the antibiotic loaded into the graft produced no adverse effects on the bone healing properties of the DBM at a lower level of antibiotic. Conclusion. This antibiotic-loaded bone void filler may represent a promising option for the delivery of local antibiotics in orthopaedic surgery. Cite this article: Bone Joint J 2016;98-B:1126–31

Introduction. When third body particles originating from bone cement or bone void fillers become trapped between articulating surfaces of joint replacements, contact surfaces may be damaged leading to accelerated wear and premature failure of the implant. In this study, the damage to cobalt chrome counterfaces by third body particles from PMMA bone cement (GMV, DePuy) and various bone void fillers was investigated; then wear tests of UHMWPE were carried out against these surfaces. Methods. Third body particles of polymerised GMV bone cement and the bone void fillers; OsteoSet (with tobramycin), Stimulan and Stimulan+ (with vancomycin and tobramycin) (provided by Biocomposites Ltd.) were trapped between an UHMWPE pin and a highly polished cobalt chrome plate. A load of 120N was applied to the pin and using an Instron materials testing machine, the plate was pulled beneath the pin to recreate third body damage [1]. The resulting surface topography of the plate was analysed using white light interferometry (Bruker NPFLEX). Pin on plate wear tests of GUR 1020 UHMWPE pins were carried out against the plates perpendicular to the direction of damage for 500,000 cycles in 25% bovine serum using a 6-station multi-axial reciprocating rig under conditions to replicate the kinematics in total knee replacement. Wear of the pins was determined by gravimetric analysis and results were compared to negative (highly polished) control plates and positive controls scratched with a diamond stylus (lip height 2µm). Statistical analysis was carried out using one-way ANOVA with significance taken at p<0.05. Results. Following damage simulation with Stimulan and Stimulan+, no scratches could be seen on the surface of the cobalt chrome plates using a stereomicroscope under 63× magnification (Figure 1). Table 1 shows that OsteoSet caused surface damage with the highest density of scratches, which had a greater mean lip height than those caused by the other third body materials. Stimulan+ caused significantly (p=0.002) fewer scratches than Osteoset and the surface damage caused by Stimulan was below the resolution of the surface analysis measurement technique used. The pin on plate wear test showed that under the test conditions used, the wear of UHMWPE was similar (p=0.108) for negative control plates and plates scratched with third body particles and a significant (p<0.001) increase in wear was only observed against the positive control plates [2]. Discussion. This study shows that third body particles originating from bone cement and bone void fillers can damage the surface of highly polished cobalt chrome plates and that materials of similar composition can cause varying severity of damage. Wear tests against plates damaged with third body particles did not significantly affect the wear of UHMWPE and to significantly increase wear, scratches needed to have a lip height of 2µm or above