Antibiotic cement coating in orthopedic surgery: a systematic review of reported clinical techniques

Background Antibiotic-containing cement and bone graft substitute-coated orthopedic implants provide the advantages of simultaneous local antibiotic delivery and internal stable fixation, aiding in both infection eradication and osseous healing. Standardized protocols pertaining to implant coating techniques in various clinical and particularly intraoperative settings are scarce, and available literature is limited. This systematic review aims to provide a summary of the available current literature reporting on custom-made coating techniques of orthopedic implants, indications, outcomes, and associated complications in clinical use. Methods A systematic search of the literature in PubMed, Medline, Embase, and Cochrane Library databases was performed in accordance with PRISMA guidelines. Articles reporting specifically on custom-made coating techniques of orthopedic implants in a clinical setting were eligible. Results A total of 41 articles with a cumulative total number of 607 cases were included. Indications for treatment mostly involved intramedullary infections after previous plate osteosynthesis or nailing. A variety of implants ranging from intramedullary nails, plates, wires, and rods served as metal cores for coating. Polymethylmethacrylate (PMMA) bone cement was most commonly used, with vancomycin as the most frequently added antibiotic additive. Chest tubes and silicone tubes were most often used to mold. Common complications are cement debonding and breakage of the metallic implant. Conclusion Adequate coating techniques can reduce the burden of treatment and be associated with favorable outcomes. Lack of general consensus and heterogeneity in the reported literature indicate that the perfect all-in-one implant coating method is yet to be found. Further efforts to improve implant coating techniques are warranted. Level of evidence III.

PMMA Bone Cements Modified with Silane-Treated and PMMA-Grafted Hydroxyapatite Nanocrystals: Preparation and Characterization

In this study, vinyltrimethoxysilane-treated hydroxyapatite (vHAP) and PMMA-grafted HAP (gHAP) were successfully prepared from original HAP (oHAP). Three kinds of HAP (oHAP, vHAP and g HAP) were used as additives for the preparation of three groups of HAP-modified PMMA bone cements (oHAP-BC, vHAP-BC and gHAP-BC). The setting, bending and compression properties of the bone cements were conducted according to ISO 5833:2002. The obtained results showed that the maximum temperature while curing the HAP-modified bone cements (HAP-BCs) decreased from 64.9 to 60.8 °C and the setting time increased from 8.1 to 14.0 min, respectively, with increasing HAP loading from 0 to 15 wt.%. The vHAP-BC and gHAP-BC groups exhibited higher mechanical properties than the required values in ISO 5833. Electron microscopy images showed that the vHAP and gHAP nanoparticles were dispersed better in the polymerized PMMA matrix than the oHAP nanoparticles. FTIR analysis indicated the polar interaction between the PO4 groups of the HAP nanoparticles and the ester groups of the polymerized PMMA matrix. Thermal gravimetric analysis indicated that mixtures of ZrO2/HAPs were not able to significantly improve the thermal stability of the HAP-BCs. DSC diagrams showed that the incorporation of gHAP to PMMA bone cement with loadings lower than 10 wt.% can increase Tg by about 2.4 °C.

PMMA bone cement containing long releasing silica-based chlorhexidine nanocarriers

Prosthetic joint infections (PJI) are still an extremely concerning eventuality after joint replacement surgery; growing antibiotic resistance is also limiting the prophylactic and treatment options. Chlorhexidine (a widely used topical non-antibiotic antimicrobial compound) coatings on silica nanoparticles capable of prolonged drug release have been successfully developed and characterised. Such nanocarriers were incorporated into commercial formulation PMMA bone cement (Cemex), without adversely affecting the mechanical performance. Moreover, the bone cement containing the developed nanocarriers showed superior antimicrobial activity against different bacterial species encountered in PJI, including clinical isolates already resistant to gentamicin. Cytocompatibility tests also showed non inferior performance of the bone cements containing chlorhexidine releasing silica nanocarriers to the equivalent commercial formulation.

Influence of Tranexamic Acid on Elution Characteristics and Compressive Strength of Antibiotic-Loaded PMMA-Bone Cement with Gentamicin

Purpose: The topical application of tranexamic acid (TXA) into the joint space during total joint arthroplasty (TJA) with no increase of complications, has been widely reported. We investigated the influence of TXA on antibiotic release, activity of the released antibiotic against a clinical isolate of S. aureus, and compressive strength of a widely used commercially prepared gentamicin-loaded cement brand (PALACOS R + G). Method: 12 bone cement cylinders (diameter and height = 6 and 12 mm, respectively) were molded. After curing in air for at least 1 h, six of the cylinders were completely immersed in 5 mL of fetal calf serum (FCS) and the other six were completely immersed in a solution consisting of 4.9 mL of FCS and 0.1 mL (10 mg) of TXA. Gentamicin elution tests were performed over 7 d. Four hundred µL of the gentamicin eluate were taken every 24 h for the first 7 d without renewing the immersion fluid. The gentamicin concentration was determined in a clinical analyzer using a homogeny enzyme immuno-assay. The antimicrobial activity of the eluate, obtained after day 7, was tested. An agar diffusion test regime was used with Staphylococcus aureus. Bacteria were grown in a LB medium and plated on LB agar plates to get a bacterial lawn. Fifty µL of each eluate were pipetted on 12-mm diameter filter discs, which were placed in the middle of the agar gel. After 24 h of cultivation at 37 °C, the zone of inhibition (ZOI) for each specimen was measured. The compressive strength of the cements was determined per ISO 5833. Results: At each time point in the gentamicin release test, the difference in gentamicin concentration, obtained from specimens immersed in the FCS solution only and those immersed in the FCS + TXA solution was not significant (p = 0.055–0.522). The same trend was seen in each of the following parameters, after 7 d of immersion: (1) Cumulative gentamicin concentration (p < 0.297); (2) gentamicin activity against S. aureus (strongly visible); (3) ZOI size (mostly > 20 mm) (p = 0.631); and (4) compressive strength (p = 0.262). Conclusions: For the PALACOS R + G specimens, the addition of TXA to FCS does not produce significant decreases in gentamicin concentration, in the activity of the gentamicin eluate against a clinical isolate of S. aureus, the zone of inhibition of S. aureus, and in the compressive strength of the cement, after 7 d of immersion in the test solution.

In Vivo Antitumor Efficacy of 17-AAG Loaded PMMA in a Multiple Myeloma Patient-Derived Xenograft Mouse Model

Multiple myeloma (MM) is a monoclonal malignancy characterized by abnormal proliferation of plasma cells. Its main clinical symptoms are osteolytic damage, severe bone pain, spinal instability, and pathological fracture and are collectively referred to as multiple myeloma bone disease (MMBD). Due to its good biomechanical properties and fast curing, polymethylmethacrylate (PMMA) bone cement is widely used for bone repair after MMBD surgery. However, whether drug-loading PMMA can inhibit tumor growth and angiogenesis has not been reported. Here, we report that 17-AAG-loaded PMMA bone cement inhibits MM growth in vivo and suppresses tumor diffusion to peripheral tissues. 17-AAG-loaded PMMA promotes MM apoptosis by downregulating Bax and active Caspase-3.

Influence of Porosity on Fracture Toughness and Fracture Behavior of Antibiotic-Loaded PMMA Bone Cement

Aseptic loosening is the most common reason for long-term revision of total joint replacement (TJR). Infection is the main reason for short-term revision of TJR. In our previous studies, experimental results showed that acrylic bone cement-loaded with antibiotics had a detrimental effect on cement strength such as bending strength, compressive strength, and fracture toughness. This result implied that the mechanical failure of antibiotic loaded bone cement was potentially related to porosity volume fraction. Hence, the objective of this study was to investigate the effect of pore size and distribution on bone cement fracture toughness. The effect of pores was analyzed using the extended Finite Element Method (X-FEM) method to model crack propagation and its modulation by pore sizes and locations. Numerically obtained load-displacement responses were compared to experimental results. We observed that crack propagation is affected by several pore parameters; as expected these include pore size and pore locations (pore-pore interactions) and are related to implicit pore-crack interactions. The experimental and numerical investigations presented in the current study contribute to a better understanding of the effect of pores on bone cement fracture toughness; key insights include the identification of a critical pore size for reduced fracture toughness, and relative insensitivity of crack propagation to stochastically distributed pore locations.

Performance of Calcium Phosphate Cements in the Augmentation of Sheep Vertebrae—An Ex Vivo Study

Oil-based calcium phosphate cement (Paste-CPC) shows not only prolonged shelf life and injection times, but also improved cohesion and reproducibility during application, while retaining the advantages of fast setting, mechanical strength, and biocompatibility. In addition, poly(L-lactide-co-glycolide) (PLGA) fiber reinforcement may decrease the risk for local extrusion. Bone defects (diameter 5 mm; depth 15 mm) generated ex vivo in lumbar (L) spines of female Merino sheep (2–4 years) were augmented using: (i) water-based CPC with 10% PLGA fiber reinforcement (L3); (ii) Paste-CPC (L4); or (iii) clinically established polymethylmethacrylate (PMMA) bone cement (L5). Untouched (L1) and empty vertebrae (L2) served as controls. Cement performance was analyzed using micro-computed tomography, histology, and biomechanical testing. Extrusion was comparable for Paste-CPC(-PLGA) and PMMA, but significantly lower for CPC + PLGA. Compressive strength and Young’s modulus were similar for Paste-CPC and PMMA, but significantly higher compared to those for empty defects and/or CPC + PLGA. Expectedly, all experimental groups showed significantly or numerically lower compressive strength and Young’s modulus than those of untouched controls. Ready-to-use Paste-CPC demonstrates a performance similar to that of PMMA, but improved biomechanics compared to those of water-based CPC + PLGA, expanding the therapeutic arsenal for bone defects. O, significantly lower extrusion of CPC + PLGA fibers into adjacent lumbar spongiosa may help to reduce the risk of local extrusion in spinal surgery.