David C. Markel

Coaxial PCL/PVA electrospun nanofibers: Osseointegration enhancer and controlled drug release device

The failure of prosthesis after total joint replacement is mainly due to dysfunctional osseointegration and implant infection. There is a critical need for orthopedic implants that promote rapid osseointegration and prevent bacterial colonization, particularly when placed in bone compromised by disease or physiology of the patients. The aim of this study was to fabricate a novel coaxial electrospun polycaprolactone (PCL)/polyvinyl alcohol (PVA) core-sheath nanofiber (NF) blended with both hydroxyapatite nanorods (HA) and type I collagen (Col) (PCL(Col)/PVA(HA)). Doxycycline (Doxy) and dexamethasone (Dex) were successfully incorporated into the PCL(Col)/PVA(HA) NFs for controlled release. The morphology, surface hydrophilicity and mechanical properties of the PCL/PVA NF mats were analyzed by scanning electron microscopy, water contact angle and atomic force microscopy. The PCL(Col)/PVA(HA) NFs are biocompatible and enhance the adhesion and proliferation of murine pre-osteoblastic MC3T3 cells. The release of Doxy and Dex from coaxial PCL(Col)/PVA(HA) NFs showed more controlled release compared with the blended NFs. Using an ex vivo porcine bone implantation model we found that the PCL(Col)/PVA(HA) NFs bind firmly on the titanium rod surface and the NFs coating remained intact on the surface of titanium rods after pullout. No disruption or delamination was observed after the pullout test. These findings indicate that PCL(Col)/PVA(HA) NFs encapsulating drugs have great potential in enhancing implant osseointegration and preventing implant infection.

Preoperative and Postoperative Opiate Use by the Arthroplasty Patient

BACKGROUNDnAs opioid use increases nationally, the arthroplasty surgeon is likely to see more patients taking opioid analgesics on initial presentation. The purpose of this study was to investigate the use of opiate medication in the preoperative and postoperative patient undergoing primary total joint arthroplasty.nnnMETHODSnFrom October 2010 to November 2011, data on 367 consecutive patients who underwent primary total joint arthroplasty were reviewed. Using the Michigan Automated Prescription System database, data were collected on opiate use from 3 months preop to 12 months postop. Patients were grouped by preoperative opiate use. Patients with ≥2 opiate prescriptions filled per 6-week period before surgery were considered chronic opiate users.nnnRESULTSnThree hundred fifteen patients fit our inclusion/exclusion criteria. There were 158 primary total knee and 157 primary total hip arthroplasty patients. At 1 year after operation, 64% of chronic opiate users were still being prescribed opiates compared with 22% of the control group (P < .001). Thirty-one percent of the chronic opiate users were discharged to an extended care facility compared to 21% of the control group (Pxa0= .123). Of all the opiate prescriptions, 77% were written by a practitioner other than the surgeon.nnnCONCLUSIONSnOpiates are frequently prescribed by providers other than the surgeon preoperatively and postoperatively. The use of opiates that were presumably prescribed to treat joint pain was continued for more than 1 year postoperatively in 64% of cases. Patients taking multiple opiates or more potent opiates preoperatively filled more prescriptions postoperatively. Chronic use of opiates negatively influenced the discharge disposition.

Poly(vinyl alcohol)/collagen/hydroxyapatite hydrogel: properties and in vitro cellular response.

The objective of this study was to develop bone-like poly(vinyl alcohol) (PVA)/hydroxyapatite (HA)/type I collagen (Col) hydrogel composites that stimulate adhesion, proliferation, and differentiation of osteoblastic cells. The hydrogel composites were prepared by mixing PVA with nanoscale HA and Col using a physical mixing method. The concentration of the components was optimized during formulation development. PVA/Col/HA hydrogels were characterized for viscoelasticity, degree of swelling, mechanical strength, embedded erythromycin drug release, and cellular response of both osteoblastic MC3T3 cells and RAW 264.7 macrophage cells. Compressive strength tests confirmed that the PVA coating possessed greater elasticity and was mechanically enhanced by the freeze-thaw treatment. PVA/Col/HA gel is biocompatible and nontoxic to MC3T3 preosteoblasts, and the reinforcement from HA and Col reduced the inflammatory response from macrophages. Our findings demonstrate that PVA composites are biocompatible, and enhance cell adhesion, proliferation, and differentiation in vitro. We propose that PVA/Col/HA hydrogels represent one of the promising implant surface coating matrices for the improvement of implant osseointegration.

Efficacy of periprosthetic erythromycin delivery for wear debris-induced inflammation and osteolysis

ObjectivesWe have reported that oral erythromycin (EM) inhibits periprosthetic tissue inflammation in a group of patients with aseptic loosening. The purpose of this study was to assess the efficacy of local, periprosthetic EM delivery in a rat model.MethodsUncoated Ti pins were press-fit into the right tibia of fourteen Sprague–Dawley rats following an intramedullar injection of UHMWPE (ultra high molecular weight polyethylene) particles. Revision surgeries were performed 2xa0months after the primary surgery. EM was applied to the Peri-Apatite™ (PA) layer of the titanium (Ti) pins. The previously implanted Ti pins were withdrawn and replaced with Ti pins coated either with (nxa0=xa07) or without (nxa0=xa07) EM. The rats were killed 1xa0month after “revision surgery”. The EM efficacy was evaluated by (MicroCT) μCT and histology.ResultsμCT analysis showed that bone volume percentage (BV/TV) was significantly higher in the EM-treated group compared to the untreated group (pxa0<xa00.05). Histological analysis showed that EM treatment inhibits UHMWPE particle-induced periprosthetic tissue inflammation compared to the untreated group.ConclusionThis study demonstrated that periprosthetic EM delivery reduced periprosthetic inflammation and improved the quality of surrounding bone.

Revision of Recalled Modular Neck Rejuvenate and ABG Femoral Implants

Modular neck femoral stems have been associated with adverse local tissue reactions (ALTR), leading to a voluntary recall, but these effects have not been well-characterized. A retrospective review of intraoperative findings and cobalt/chromium levels was performed in 103 hips undergoing revision for ALTR. The average preoperative serum cobalt level was 7.6 μg/L (range 1.1-23 μg/L) and chromium level was 1.8 μg/L (range 0.1-6.8 μg/L). Metallic sludge was noted in 100%, synovitis in 98%, pericapsular rind in 82%, and calcar erosion in 85%. An osteotomy was required for removal in 44%. We concluded that revision of modular neck femoral stems is associated with increased preoperative metal ion levels and stem-neck corrosion. Despite advanced stem explantation techniques, osteotomy was frequently required, leading to increased morbidity.

A novel strontium-doped calcium polyphosphate/erythromycin/poly(vinyl alcohol) composite for bone tissue engineering.

It is our goal to develop bactericidal bone scaffolds with osteointegration potential. In this study, poly(vinyl alcohol) (PVA) coating (7%) was applied to an erythromycin (EM)-impregnated strontium-doped calcium polyphosphate (SCPP) scaffold using a simple slurry dipping method. MicroCT analysis showed that PVA coating reduced the average pore size and the percentage of pore interconnectivity to some extent. Compressive strength tests confirmed that the PVA coating significantly increased material elasticity and slightly enhanced the scaffold mechanical strength. It was also confirmed that the PVA coatings allowed a sustained EM release that is controlled by diffusion through the intact PVA hydrogel layer, irrespective of the drug solubility. PVA coating did not inhibit the EM bioactivity when the scaffolds were immersed in simulated body fluid for up to 4 weeks. EM released from SCPP-EM-PVA composite scaffolds maintained its capability of bacterial growth (S. aureus) inhibition. PVA coating is biocompatible and nontoxic to MC3T3 preosteoblast cells. Furthermore, we found that SCPP-EM-PVA composite scaffolds and their eluants remarkably inhibited RANKL-induced osteoclastogenesis in a murine RAW 264.7 macrophage cell line. Thus, this unique multifunctional bioactive composite scaffold has the potential to provide controlled delivery of relevant drugs for bone tissue engineering.

A novel alkali metals/strontium co-substituted calcium polyphosphate scaffolds in bone tissue engineering

Our purpose of this study is to develop potassium or sodium/strontium co-substituted calcium polyphosphate (K/Sr-CPP or Na/Sr-CPP) bioceramics in application of bone repairing scaffold. The incorporation of K, Na, and Sr into CPP substrate via a calcining-sintering process was confirmed by X-ray diffractometry and inductively coupled plasma atomic emission spectroscopy. In vitro degradation study of co-substituted CPP indicated the incorporation of alkali metal elements promoted the degradability of CPP, and the scanning electron microscope showed the apatite-like minerals were precipitated on the surface of co-substituted CPP. The compress resistant strength of co-substituted CPP was elevated by dopants. The MTT assay and confocal laser-scanning microscope on osteoblasts culturing with co-substituted CPP showed no cytotoxicity. The cell proliferation on co-substituted CPP was even better than others. Thus, this co-substituted CPP bioceramics might have potential of applications in orthopedic field.

Constrained Acetabular Liners Cemented Into Cages During Total Hip Revision Arthroplasty

The combination of acetabular bone loss and hip instability is challenging. Sixteen patients underwent revision total hip arthroplasty using constrained acetabular liners cemented into cages. The average follow-up was 28 months (range, 24-60 months). Clinical evaluation was obtained using the Harris hip score along with radiographic data. At latest follow-up, 13 patients were available for evaluation. Although the average postoperative Harris hip score was 62 points, which was better than the preoperative score of 27 points, the overall radiographic failure rate was 23%. The combination of poor acetabular bone stock and altered stresses from the increased constraint likely led to the poor outcome. We would only recommend use of a cemented, constrained acetabular liner in combination with a protrusio cage as a bail out or salvage procedure.

MRI Findings Associated with Recalled Modular Femoral Neck Rejuvenate and ABG Implants

MARS-MRI is suggested for the diagnosis of adverse local tissue reactions (ALTR) in patients with recalled femoral stems with modular necks, but there has been no major study looking at MARS-MRI findings in this population. A retrospective review was performed on 312 patients who received a modular neck hip implant between October 2007 and February 2012. 62% of patients had intra-articular effusions, with 27% containing debris. Extra-capsular effusions were present in 35% of hips. 54% had synovitis and 5.4% had osteolysis. Tendinopathy and tendon disruption was present in the gluteus medius (58%/12%), hamstring (56%/12%), gluteus minimus (38%/7.7%) and iliopsoas (7.1%/4.8%). Abnormal MARS-MRI findings are associated with modular neck femoral components and can suggest underlying ALTR. MARS-MRI abnormalities merit serious consideration in this population.

Effect of erythromycin-doped calcium polyphosphate scaffold composite in a mouse pouch infection model

We previously showed that strontium-doped calcium polyphosphate (SCPP) scaffold with poly(vinyl alcohol) (PVA) coating extended the impregnated erythromycin (EM) release. In this study, we examined the bactericidal effect of EM-doped SCPP (SCPP(EM) ) scaffolds with PVA coating in a Staphylococcus aureus (S. aureus) infected mouse pouch. SCPP scaffolds with or without 5% EM, and SCPP(EM) scaffolds coated with PVA (with or without 5% EM) were prepared. Scaffolds were implanted in the pouch of BALB/c mice, followed by inoculation of 1 × 10(3) colony-forming units of S. aureus. Mice were sacrificed 14 days after surgery. Pouch tissues and scaffolds were collected for histology, scanning electron microscopy, and microbiological analysis. In the absence of SCPP scaffolds, the pouch infection was eliminated by the host immune surveillance. In the presence of SCPP scaffolds, both the pouch tissues and scaffolds were infected, but SCPP(EM) scaffolds successfully inhibited bacterial growth. Although PVA coating of SCPP(EM) scaffolds enhanced bacterial growth, incorporation of EM into PVA coating inhibited growth. In conclusion, BALB/c mice were capable of eradicating a low grade S. aureus infection. SCPP protected S. aureus growth from host immune surveillance. Though PVA coating sustained EM release in vitro, it was unable to inhibit bacterial growth because PVA gel matrix provided a temporary shelter for bacteria to grow and slowed the EM release from SCPP scaffold. To guarantee a sufficient inhibition of bacterial growth at the initial stage, embedding EM or other antibiotics in the PVA coating is also essential.