Nicky Bertollo

Corticosterone selectively targets endo-cortical surfaces by an osteoblast-dependent mechanism

BACKGROUND The pathogenesis of glucocorticoid-induced osteoporosis remains ill defined. In this study, we examined the role of the osteoblast in mediating the effects of exogenous glucocorticoids on cortical and trabecular bone, employing the Col2.3-11βHSD2 transgenic mouse model of osteoblast-targeted disruption of glucocorticoid signalling. METHODS Eight week-old male transgenic (tg) and wild-type (WT) mice (n=20-23/group) were treated with either 1.5 mg corticosterone (CS) or placebo for 4 weeks. Serum tartrate-resistant acid phosphatase 5b (TRAP5b) and osteocalcin (OCN) were measured throughout the study. Tibiae and lumbar vertebrae were analysed by micro-CT and histomorphometry at endpoint. RESULTS CS suppressed serum OCN levels in WT and tg mice, although they remained higher in tg animals at all time points (p<0.05). Serum TRAP5b levels increased in WT mice only. The effect of CS on cortical bone differed by site: At the endosteal surface, exposure to CS significantly increased bone resorption and reduced bone formation, resulting in a larger bone marrow cavity cross-sectional area (p<0.01). In contrast, at the pericortical surface bone resorption was significantly decreased accompanied with a significant increase in pericortical cross-sectional area (p<0.05) while bone formation remained unaffected. Vertebral cortical thickness and area were reduced in CS treatment mice. Tg mice were partially protected from the effects of exogenous CS, both on a cellular and structural level. At the CS doses used in this study, trabecular bone remained largely unaffected. CONCLUSION Endocortical osteoblasts appear to be particularly sensitive to the detrimental actions of exogenous glucocorticoids. The increase in tibial pericortical cross-sectional area and the according changes in pericortical circumference suggest an anabolic bone response to GC treatment at this site. The protection of tg mice from these effects indicates that both catabolic and anabolic action of glucocorticoids are, at least in part, mediated by osteoblasts.

Plasma-sprayed titanium coating to polyetheretherketone improves the bone-implant interface

BACKGROUND CONTEXT Rapid and stable fixation at the bone-implant interface would be regarded as one of the primary goals to achieve clinical efficacy, regardless of the surgical site. Although mechanical and physical properties of polyetheretherketone (PEEK) provide advantages for implant devices, the hydrophobic nature and the lack of direct bone contact remains a limitation. PURPOSE To examine the effects of a plasma-sprayed titanium coated PEEK on the mechanical and histologic properties at the bone-implant interface. STUDY SETTING A preclinical laboratory study. METHODS Polyetheretherketone and plasma-sprayed titanium coated PEEK implants (Ti-bond; Spinal Elements, Carlsbad, CA, USA) were placed in a line-to-line manner in cortical bone and in a press-fit manner in cancellous bone of adult sheep using an established ovine model. Shear strength was assessed in the cortical sites at 4 and 12 weeks, whereas histology was performed in cortical and cancellous sites at both time points. RESULTS The titanium coating dramatically improved the shear strength at the bone-implant interface at 4 weeks and continued to improve with time compared with PEEK. Direct bone ongrowth in cancellous and cortical sites can be achieved using a plasma-sprayed titanium coating on PEEK. CONCLUSIONS Direct bone to implant bonding can be achieved on PEEK in spite of its hydrophobic nature using a plasma-sprayed titanium coating. The plasma-sprayed titanium coating improved mechanical properties in the cortical sites and the histology in cortical and cancellous sites.

A comparison of the thermal properties of 2- and 3-fluted drills and the effects on bone cell viability and screw pull-out strength in an ovine model

BACKGROUND Drilling of bone is associated with an increase in temperature of the surrounding bone which may result in osteonecrosis. METHODS In this study, cutting efficiency and thermal properties of one 2-fluted drill and two 3-fluted drills were determined in vitro using a porcine model. Drills were then used to create pilot holes in an in vivo ovine model to facilitate implantation of pedicle screws. The effect of the characteristic thermal profiles of each drill on cortical bone cell viability and screw pull-out strength was then assessed. FINDINGS Cutting efficiencies of both 3-fluted designs were found to be greater than that of the 2-fluted drill, but this did not translate into a decrease in the maximum temperatures during drilling for both drills. Histologically, no empty osteocyte lacunae were seen at 2 or 4 weeks, suggesting that temperatures were not sufficiently high enough to induce thermonecrosis in the ovine tibia. No differences were found in the pull-out strength of the screws. INTERPRETATION Both 2- and 3-fluted drills are currently in clinical use. Despite the theoretical advantage that 3-fluted drills possess over their 2-fluted counterparts, there is a lack of evidence in the literature in support of their use. In this study the observed increases in cutting efficiency of the 3-fluted drills tested did not translate into a reduction in heat generation or improvement in bone healing or screw fixation.

Performance of a knotless four-strand flexor tendon repair with a unidirectional barbed suture device: a dynamic ex vivo comparison

With increased numbers of reports using barbed sutures for tendon repairs we felt the need to design a specific tendon repair method to draw the best utility from these materials. We split 30 sheep deep flexor tendons in two groups of 15 tendons. One group was repaired with a new four-strand barbed suture repair method without knot. The other group was repaired with a conventional four-strand cross-locked cruciate repair method (Adelaide repair) with knot. Dynamic testing (3–30 N for 250 cycles) and additional static pull to failure was performed to investigate gap formation and final failure forces. The barbed suture repair group showed higher resistance to gap formation throughout the test. Additionally final failure force was higher for the barbed suture group compared with the conventional repair group. When used appropriately, barbed suture materials could be beneficial to use in tendon surgery, especially with regard to early loading of the repair site and gap formation.

Influence of electron beam melting manufactured implants on ingrowth and shear strength in an ovine model.

Arthroplasty has evolved with the application of electron beam melting (EBM) in the manufacture of porous mediums for uncemented fixation. Osseointegration of EBM and plasma-sprayed titanium (Ti PS) implant dowels in adult sheep was assessed in graduated cancellous defects and under line-to-line fit in cortical bone. Shear strength and bony ingrowth (EBM) and ongrowth (Ti PS) were assessed after 4 and 12 weeks. Shear strength of EBM exceeded that for Ti PS at 12 weeks (P = .030). Ongrowth achieved by Ti PS in graduated cancellous defects followed a distinctive pattern that correlated to progressively decreasing radial distances between defect and implant, whereas cancellous ingrowth values at 12 weeks for the EBM were not different. Osteoconductive porous structures manufactured using EBM present a viable alternative to traditional surface treatments.

In vivo implant fixation of carbon fiber-reinforced PEEK hip prostheses in an ovine model

Carbon fiber‐reinforced polyetheretherketone (CFR/PEEK) is theoretically suitable as a material for use in hip prostheses, offering excellent biocompatibility, mechanical properties, and the absence of metal ions. To evaluate in vivo fixation methods of CFR/PEEK hip prostheses in bone, we examined radiographic and histological results for cementless or cemented CFR/PEEK hip prostheses in an ovine model with implantation up to 52 weeks. CFR/PEEK cups and stems with rough‐textured surfaces plus hydroxyapatite (HA) coatings for cementless fixation and CFR/PEEK cups and stems without HA coating for cement fixation were manufactured based on ovine computed tomography (CT) data. Unilateral total hip arthroplasty was performed using cementless or cemented CFR/PEEK hip prostheses. Five cementless cups and stems and six cemented cups and stems were evaluated. On the femoral side, all cementless stems demonstrated bony ongrowth fixation and all cemented stems demonstrated stable fixation without any gaps at both the bone‐cement and cement‐stem interfaces. All cementless cases and four of the six cemented cases showed minimal stress shielding. On the acetabular side, two of the five cementless cups demonstrated bony ongrowth fixation. Our results suggest that both cementless and cemented CFR/PEEK stems work well for fixation. Cup fixation may be difficult for both cementless and cemented types in this ovine model, but bone ongrowth fixation on the cup was first seen in two cementless cases. Cementless fixation can be achieved using HA‐coated CFR/PEEK implants, even under load‐bearing conditions.

Novel Surface Modifications of Carbon Fiber-Reinforced Polyetheretherketone Hip Stem in an Ovine Model

A carbon fiber-reinforced polymer (CFRP) is theoretically a suitable material for use in an uncemented hip prosthesis considering it can provide isoelastic environment with the surrounding bone, adequate fatigue strength, and a metal-free radiographic evaluation. To date, the selection of polymer material and optimization of both design and surface finish of the prostheses for osseointegration has not been accomplished. This study examined radiographic and histologic results of an uncemented CFRP stem manufactured from carbon fiber-reinforced polyetheretherketone (CFR/PEEK) with a roughened surface and a bioactive treatment in an adult ovine model following a 12-month implantation period. A unilateral hemiarthroplasty of the hip was performed using the CFRP stem or a titanium stem as a control. Four cases with the CFRP stem and five cases with titanium stem were evaluated. Bone on-growth fixation was achieved in two cases with the CFRP stem and in all the cases with the titanium stem. The CFRP cases showed minimal stress shielding while three of five cases with the titanium stem demonstrated typical osteopenia associated with stiff metal stems. Bone on-growth to the uncemented CFRP stem was achieved by using the CFR/PEEK for the material and modifying the surface design and the bioactive surface finish. Bone resorption and osteopenia observed with the Ti stems was not found with the CFRP design.

Osseointegration of porous titanium implants with and without electrochemically deposited DCPD coating in an ovine model

BackgroundUncemented fixation of components in joint arthroplasty is achieved primarily through de novo bone formation at the bone-implant interface and establishment of a biological and mechanical interlock. In order to enhance bone-implant integration osteoconductive coatings and the methods of application thereof are continuously being developed and applied to highly porous and roughened implant substrates. In this study the effects of an electrochemically-deposited dicalcium phosphate dihydrate (DCPD) coating of a porous substrate on implant osseointegration was assessed using a standard uncemented implant fixation model in sheep.MethodsPlasma sprayed titanium implants with and without a DCPD coating were inserted into defects drilled into the cancellous and cortical sites of the femur and tibia. Cancellous implants were inserted in a press-fit scenario whilst cortical implants were inserted in a line-to-line fit. Specimens were retrieved at 1, 2, 4, 8 and 12 weeks postoperatively. Interfacial shear-strength of the cortical sites was assessed using a push-out test, whilst bone ingrowth, ongrowth and remodelling were investigated using histologic and histomorphometric endpoints.ResultsDCPD coating significantly improved cancellous bone ingrowth at 4 weeks but had no significant effect on mechanical stability in cortical bone up to 12 weeks postoperatively. Whilst a significant reduction in cancellous bone ongrowth was observed from 4 to 12 weeks for the DCPD coating, no other statistically significant differences in ongrowth or ingrowth in either the cancellous or cortical sites were observed between TiPS and DCPD groups.ConclusionThe application of a DCPD coating to porous titanium substrates may improve the extent of cancellous bone ingrowth in the early postoperative phase following uncemented arthroplasty.

Effect of surgical fit on integration of cancellous bone and implant cortical bone shear strength for a porous titanium.

Porous scaffold dowels of Ti(6)Al(4)V were prepared and implanted into cancellous and cortical bone sites in adult sheep. Cancellous implants were examined under gap, line-to-line, and press-fit conditions, whereas line-to-line implantation was used in cortical sites. Cortical shear strength increased significantly with time and reached 26.1 ± 8.6 MPa at 12 weeks, accompanied by a concomitant increase in bone integration and remodeling. In cancellous sites, bone integration was well established at 4 and 12 weeks under conditions of press-fit and line-to-line match between implant and surgical defect. New bone growth was also found in the gap conditions, although to a lesser extent. These findings suggest that the porous Ti(6)Al(4)V could prove an effective scaffold material for uncemented fixation in cortical and cancellous sites.

The effect of sterilization on the dynamic mechanical properties of paired rabbit cortical bone.

The optimal sterilization method for load bearing allografts remains a clinical concern. Recently, supercritical carbon dioxide (SCCO2) treatments have been shown to be capable of terminally sterilizing a range of bacteria and viruses, while preserving the static mechanical properties of cortical bone. This study evaluated the effect of SCCO2 treatment compared with two doses of gamma irradiation, on clinically relevant dynamic mechanical properties of cortical bone. Quasi-static testing was also performed to compare the impairment of treatment. Whole paired adult rabbit humeri were dissected and randomly assigned into either SCCO2 Control, SCCO2 Additive or gamma irradiation at 10 or 25kGy treatment groups. The bones were treated and mechanically tested in three-point bending, with the lefts acting as controls for the treated rights. Maximum load, energy to failure and stiffness were evaluated from static tests. The number of cycles to failure was determined for fatigue at 6-60% of the ultimate load. This study found that SCCO2 treatment with or without additive did not alter static or dynamic mechanical properties. Gamma irradiation had a deleterious dose dependent effect, with statistically significant (p<0.05) reductions in all static mechanical parameters at 25kGy. This effect was increased in fatigue with statistically significant decreases in both the 10 and 25kGy dose groups. This study highlights the expediency of SCCO2 treatment for load bearing bone allograft processing as terminal sterilization can be achieved while maintaining both the quasi-static and dynamic mechanical properties of the graft.