Bone Adhesion Research Articles

A Comparison of Mechanical Properties of Lumbar Bilateral Implants Manufactured by Additive and Conventional Technologies

Spinal implants are mechanical equipments that facilitate fusion, correct deformities, and stabilize and strengthen the spine. To make an implant efficient, it has to endure without any failure, especially mechanical damage, stand all the static and dynamic loads incurred in spine during everyday activities, and maintain the necessary position of motive segments during the bone adhesion. [1] Human spine is exposed to the highest load in the lumbar section [2]; therefore, lumbar bilateral implants require higher attention in terms of mechanical parameters verification. The main objective of this paper was to compare mechanical properties of lumbar bilateral systems using the spinal implants manufactured by the conventional method and the Direct Metal Laser Sintering method (DMLS). Detection of mechanical properties enables the assessment of possible replacement of commercial manufacture with the DMLS manufacture. On the basis of the ASTM F1717 standards providing the essentials for the comparison of mechanical properties of spinal systems, twenty mechanical compression tests were carried out. Mechanical tests were carried out using 20 spinal bars with the diameter of 11 mm and the fastening length of 260 mm, manufactured by the DMLS technology while using the EOSINT M280 equipment (EOS, Germany), and 20 identical spinal bars manufactured by the conventional technology. Results obtained in mechanical compression tests indicate that both manufacture methods are comparable and there are no significant differences between them, as for the strength characteristics. Other trials will be focused on static tensile tests and cyclical tests of lumbar bilateral systems.

Abstract 37: Bone metastases in renal cell carcinoma are predicted by characteristics of the primary tumor

Abstract Introduction: The poor prognosis of renal cell carcinoma (RCC) is caused by a high risk of metastasis. 30 % of all RCC patients develop bone metastases during course of disease. The outcome of RCC patients with bone metastases is poor so that a prediction would be of advantage. The aim of this study was to elucidate the mechanisms that lead to an organ specific metastasis of RCC in bones and probably predict bone metastasis. Methods: In 30 RCC tissue specimens and 9 RCC primary cell lines collected from patients who had developed no metastases, lung or bone metastases within 5 years after nephrectomy (each 10 RCC tissue specimens, each 3 RCC cell lines) expression and/or activity of 46 cellular signalling molecules were quantified by a phospho kinase array and Western blot analyses. As steps of metastasis, migration of the primary RCC cells was analysed in a Boyden chamber with 10 µg/ml fibronectin as chemotaxin, adhesion to extracellular matrix compounds fibronectin, collagen I and IV was determined after cell staining with crystal violet. Results: In RCC tissue specimens and primary cells from patients who developed bone metastases a higher expression of alpha5 integrins, higher activity of Akt and FAK as well as a lower expression of PTEN was detected, compared to those from patients without or with lung metastases. According to these results we observed an enhanced chemotactic migration (13-fold) of bone metastatic RCC cells and adhesion to fibronectin (6-fold) or collagen type I (8-fold) - both components of the bone matrix. Conclusion: These results show that specific characteristics like the expression and activity of cell signalling mediators and the cellular behaviour of the primary tumor determine the location of the subsequent metastasis in RCC and could be used as prognostic marker for bone metastasis. This should be considered during follow-up care. Funded by the Wilhelm Sander Foundation Citation Format: Elke Schneider, Tobias Haber, Frederick C. Roos, Christian Hampel, Kerstin Junker, Joachim W. Thüroff, Walburgis Brenner. Bone metastases in renal cell carcinoma are predicted by characteristics of the primary tumor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 37. doi:10.1158/1538-7445.AM2014-37

Engineering of cell membranes with a bisphosphonate-containing polymer using ATRP synthesis for bone targeting

The field of polymer-based membrane engineering has expanded since we first demonstrated the reaction of N-hydroxysuccinimide ester-terminated polymers with cells and tissues almost two decades ago. One remaining obstacle, especially for conjugation of polymers to cells, has been that exquisite control over polymer structure and functionality has not been used to influence the behavior of cells. Herein, we describe a multifunctional atom transfer radical polymerization initiator and its use to synthesize water-soluble polymers that are modified with bisphosphonate side chains and then covalently bound to the surface of live cells. The polymers contained between 1.7 and 3.1 bisphosphonates per chain and were shown to bind to hydroxyapatite crystals with kinetics similar to free bisphosphonate binding. We engineered the membranes of both HL-60 cells and mesenchymal stem cells in order to impart polymer-guided bone adhesion properties on the cells. Covalent coupling of the polymer to the non-adherent HL-60 cell line or mesenchymal stem cells was non-toxic by proliferation assays and enhanced the binding of these cells to bone.

The role of surface free energy in osteoblast–biomaterial interactions

The clinical success of many orthopaedic implants relies on good integration between the implant and adjacent bone. As stabilising bone grows not only to the implant, but from it, the quick adhesion of bone forming cells called osteoblasts, their appropriate differentiation and ability to form mineralised bone are vital to achieve a good clinical outcome. Surface free energy can be thought of as a measure of the ‘unsatisfied bond energy’ resulting from ‘dangling bonds’ exposed at a material's surface. This unsatisfied bond energy affects protein adsorption and cell attachment, and thus controls the early stages of cell–biomaterial interactions and ultimately implant fixation. When water, proteins, or cells approach a surface, their surface domains align to minimise the overall surface free energy of the interface. Determining these interactions, however, is not simple. While contact angle measurements on flat surfaces can predict some surface free energy-related interactions, this is not the case when surface topography is modified. Here, the authors review how surface free energy can be altered on self-assembled monolayers, polymers, metals and ceramics and clarify the differences between measurements of surface free energy and wettability. The authors also review how surface free energy affects protein interactions and osteoblast behaviour. The result is a clearer understanding of the effect of surface free energy on cell behaviour and an unambiguous need for further studies that isolate such effects.

Заживление перелома в условиях интрамедуллярного введения спиц с покрытием из гидроксиапатита

To study morphological features of the bone formation process in consolidation of fractures of long tubular bones in conditions of intramedullary wires insertion with bioactive calcium-phosphate coating of hydroxyapatite. In experimental study in dogs was simulated open comminuted tibia fracture and performed intramedullary insertion of wires with hydroxyapatite coating. Using light and electron microscopy, using X-ray electron microprobe microanalyses were studied bone regenerates in 14-360 days after surgery. It was found that around wires there is a formation of an area of active reparative bone formation and angiogenesis, bone shaped case with the properties of the conductor and inducer of osteogenesis. Fracture consolidation is carried out in the early stages of the primary type without formation of cartilage and connective tissue in the bone adhesion. Study results testify that intramedullary wires with hydroxyapatite coating positively influence on the process and intensity of reparative bone formation in fracture healing.

Advances in calcium phosphate coatings - anodic spark deposition: a review

High voltage anodization of titanium in the presence of an electrolytic medium containing calcium and phosphate ions has shown improved osteointegration and biocompatibility compared to untreated titanium. Processing parameters influence the unique porous microstructure developed during anodization. These parameters tailor the specific properties of the surface to achieve improved osseointegration of an implant. In addition, subsequent treatment following anodization further alters the microstructure. Numerous studies have examined the influence of these properties on the cellular response and the mechanical properties in terms of coating adhesion and pull-out strength in bone; however, there are conflicting reports on the cellular responses. This review examines those processing parameters and the related influence on cellular responses and mechanical properties. In addition, this review provides a summary of published reports regarding the work related to the advancement of calcium phosphate coatings achieved through high voltage anodization.

Paclitaxel-loaded polyphosphate nanoparticles: a potential strategy for bone cancer treatment.

While it has been shown that phosphates can target molecules and nanocarriers to bone we herein demonstrate the preparation of polyphosphate nanoparticles loaded with paclitaxel using a simple miniemulsion/solvent-evaporation technique as a model for chemotherapeutic delivery. Polyphosphates exhibit much higher structural versatility, relying on the pentavalence of the phosphorus center compared to conventional polyesters. This versatility allows for the development of new degradable polymeric carriers with inherent bone adhesion ability by the interaction of the nanoparticles with a calcium phosphate material used for bone regeneration. The novel polyphosphate nanoparticles were investigated in detail with respect to their size distribution, zeta-potential, thermal and morphological properties and were further proven to be efficiently loaded with a hydrophobic drug (up to 15 wt%). The in vitro cytotoxicity was assessed against human cancer cell lines (HeLa and Saos-2), and the paclitaxel-loaded nanoparticles showed a similar cytotoxicity profile similar to the commercially available formulation Taxomedac® and the pure paclitaxel for loading ratios of 10 wt% but additionally proved efficient adhesion on calcium phosphate granules allowing drug delivery to bone. This first report demonstrates that polyphosphate nanoparticles are promising materials for the development of systemic or local bone cancer treatment, even by direct application or by formation of composites with calcium phosphate cements.

Biomimetic biphasic 3‐D nanocomposite scaffold for osteochondral regeneration

Scaffold‐based interfacial tissue engineering aims to not only provide the structural and mechanical framework for cellular growth and tissue regeneration, but also direct cell behavior. Due to the disparity in composition of the osteochondral (cartilage and bone) interface, this work has developed a novel biomimetic biphasic nanocomposite scaffold integrating two biocompatible polymers containing tissue‐specific growth factor‐encapsulated core–shell nanospheres. Specifically, a poly(caprolactone) (PCL)‐based bone layer was successfully integrated with a poly(ethylene glycol) (PEG) hydrogel cartilage layer. In addition, a novel nanosphere fabrication technique for efficient growth factor encapsulation and sustained delivery via a wet coaxial electrospray technique was developed. Human bone marrow mesenchymal stem cell (hMSC) adhesion, osteogenic, and chondrogenic differentiation were evaluated. Our in vitro results showed significantly improved hMSC adhesion and differentiation in bone and cartilage layers, respectively. Studies have demonstrated promising results with novel biphasic nanocomposite scaffold for osteochondral tissue regeneration, thus, warranting further studies. © 2013 American Institute of Chemical Engineers AIChE J 60: 432–442, 2014

Brushite and Self‐Healing Flexible Polymer‐Modified Brushite Bone Adhesives for Fibular Osteotomy Repair

The study aim was to compare in vitro properties of two experimental bone adhesives (brushite cement and polymer‐modified brushite composite) and then assess their in vivo suitability for fixation of a fibular osteotomy using a lapine model. The composite was produced by replacement of the aqueous phase of the brushite cement (800 × 10−3 M citric acid) by polypropylene glycol‐co‐lactide dimethacrylate. FTIR showed this modification enabled pre‐mixing and better control of set through light activated polymer crosslinking instead of the acid–base brushite reaction. Raman confirmed the brushite component [equimolar monocalcium phosphate (MCPM) and β‐tricalcium phosphate (β‐TCP)] of the composite could react upon water‐sorption to enable long‐term “bulk composite self‐healing.” SEM demonstrated precipitation of brushite crystals in cell culture medium on the composite surface (“surface self‐healing”) and improved cell attachment. The composite was considerably more flexible than the cement (33% strain before yield compared to 4.6% before sharp brittle fracture). This flexibility was used to explain the more complete union of the fibula osteotomy and high callus index observed with composite use. The presence of cartilage at the osteotomy site in one fibula treated with brushite cement, however, indicated the absence of complete bone healing in this case. Raman mapping also confirmed the composite enabled more rapid mineralization of the fracture site compared with the cement. Both materials provided immediate fixation in vivo. More surprisingly both brushite and adhesive composite showed complete degradation by 5 weeks in vivo enabling complete union particularly with the adhesive composite within this time.

Novel bone adhesives: a comparison of bond strengths in vitro

Fracture fixation using adhesive is a promising alternative in craniofacial surgeries, replacing the plates and screws system. The advantages include the ease of application and avoidance of drilling holes that may weaken the bone and cause fractures. In this study the bond strengths of selected adhesives were evaluated and compared with resorbable plates and screws. Four adhesives, octyl-cyanoacrylate, N-butyl-cyanoacrylate, a novel methyl-methacrylate, and a novel cyanoacrylate derivative, were tested for their microtensile and shear bond strengths. The bone samples were cut into rectangular bars and bonded with selected adhesives for microtensile testing. For the shear bond test, paired bars were bonded at the overlap, while two other sets of bars were attached by a Lactosorb plate using either adhesive or screws. Data were analysed by analysis of variance (ANOVA). The microtensile bond strengths of N-butyl-cyanoacrylate, novel cyanoacrylate derivative, and novel methyl-methacrylate derivative were significantly greater than octyl-cyanoacrylate. When bone sections were fixed with resorbable plates and adhesives, shear bond strength was significantly greater for N-butyl-cyanoacrylate than plate and screws, while the bond strengths of other adhesives were comparable with the plate and screws. N-Butyl cyanoacrylate was shown to have the greatest potential for fixation of fractured bone in craniofacial surgical applications.

Effects of dimethylolpropionic acid modification on the characteristics of polyethylene terephthalate fibers

Polyethylene terephthalate (PET) fibers are widely used in the preparation of artificial ligaments. However, due to their lack of hydrophilicity, PET fibers have low biocompatibility, which usually results in the poor biological activity of the products. In the present study, in order to improve the hydrophilicity and biocompatibility of PET fibers, we modified their surface using dimethylolpropionic acid (DMPA). Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), tensile testing and cell culture were employed to observe the effects of DMPA modification on the characteristics of the DMPA-PET fibers. In contrast to the original PET fibers, the surface of the DMPA-PET fibers became rough as demonstrated by SEM. The FTIR spectrum further confirmed that a number of hydrophilic groups were formed on the surface of DMPA-PET. However, there were no significant changes in crystallinity and tensile strength between the PET and the DMPA-PET fibers as revealed by DSC and XRD (P>0.05). Finally, the cell co-culture test revealed that the adhesion and proliferation of bone marrow‑derived stromal cells increased greatly on the DMPA-PET fibers compared to those on the original PET fibers (P<0.05). These results demonstrate that DMPA-PET fibers have significant potential as a material for the development of artificial ligaments.

Surgical treatment of patients with osteoarthritis of the ankle joint

Aim. To evaluate the results of treatment using the authors’ proposed method of arthrodesis of the ankle and subtalar joints, based on the combination of bone grafting with compression in the Ilizarov apparatus. Methods. Conducted was a clinical and radiographic evaluation of the results of arthrodesis in the Ilizarov apparatus in 286 patients with osteoarthritis of the ankle and subtalar joints (during the last 15 years). 36 (12.6%) patients (the main group) were operated on using the authors’ proposed technique. Results. Bone adhesion as a result of arthrodesis was achieved in all patients of the main group. Excellent functional results were achieved in 11 out of 36 patients (30.5%), good results - in 22 (61.1%) patients, satisfactory results - in 3 (8.4%) patients. Bone adhesion as a result of arthrodesis in 250 patients of the comparison group was achieved in 243 patients (97.2%). In this group excellent functional results were achieved in 76 out of 250 patients (30.4%), good results - in 145 (58%) patients, satisfactory results - in 21 (8.4%) patients, poor results - in 8 (3.2%) patients. Conclusion. The proposed method of biarticular arthrodesis makes it possible to improve the trophism of the arthrodesis zone, to conduct the correction of posttraumatic deformities in the region of the ankle and subtalar joints, provides a durable and solid bone ankylosis of the ankle and subtalar joints, and makes it possible to achieve adhesion even in severe forms of osteoarthritis of the ankle and subtalar joints.

The histological evaluation of osseointegration of surface enhanced microimplants immediately loaded in conjunction with sinuslifting in humans

The aim was to investigate histomorphometrically whether or not implant surface nanotopography improves the bone response under immediate loading simultaneous to sinus grafting. Dual acid-etched titanium microimplants with/without crystalline surface deposition of calcium phosphate particles were placed in bilateral sinuslift areas grafted with a mixture of iliac crest bone and BioOss. Surface topography of microimplants was characterized using interferometry. Loaded microimplants (MsL) were immobilized in a provisional bridge supported by four normal size implants. Some patients had unloaded microimplants as controls (MsU). Biopsies were trephined after 2 or 4months and histomorphometric analysis of bone area (BA) and bone-to-implant contact (BC) was performed. Nonparametric methods for dependent data were used to compare effect of surface modification, and healing time (2 vs. 4months). A total of 53 biopsies were available from 13 patients. A total of 4/28 and 1/11 MsL failed after resp. 2 and 4months vs. 0/6 and 1/5 MsU. Many loaded biopsies were damaged at the apical portion and showed no bone adhesion. MsL decreased in BA from coronal to apical from 2 to 4months; Coronal>Middle (P=0.047), Coronal>Apical (P<0.001) and Middle>Apical (P<0.001). This gradual decrease was not observed for BC; Coronal<Middle and Middle>Apical (P<0.001). Only the middle part showed significant bone contact after 2months. For MsL there was no statistically significant difference between surface or time indicating that improvement of osseointegration over time due to maturation of the graft was poor. The MsU did not show any difference between Osseotite and Nanotite for BIC and BA (P>0.05) but doubled both their BA and BIC (P<0.05) between 2 and 4months. Osseointegration in sinus-grafted bone mixed with BioOss was poor irrespective of healing time or nanotopographical surface modification. The apex of MsL showed minimal bone contact suggesting that the graft does not add to the loading capacity. Surface enhancement was not beneficial despite the enlarged surface area. Overloading, most critical coronally of an implant, increases risks for implant failure and jeopardizes bone healing especially under immediate loading conditions with high load.

Mode III cleavage of a coin-shaped titanium implant in bone: Effect of friction and crack propagation

Endosseous cementless implants are widely used in orthopaedic, maxillofacial and oral surgery. However, failures are still observed and remain difficult to anticipate as remodelling phenomena at the bone–implant interface are poorly understood. The assessment of the biomechanical strength of the bone–implant interface may improve the understanding of the osseointegration process.An experimental approach based on a mode III cleavage mechanical device aims at understanding the behaviour of a planar bone–implant interface submitted to torsional loading. To do so, coin-shaped titanium implants were inserted on the tibiae of a New Zealand white rabbit for seven weeks. After the sacrifice, mode III cleavage experiments were performed on bone samples. An analytical model was developed to understand the debonding process of the bone–implant interface. The model allowed to assess the values of different parameters related to bone tissue at the vicinity of the implant with the additional assumption that bone adhesion occurs over around 70% of the implant surface, which is confirmed by microscopy images. The approach allows to estimate different quantities related to the bone–implant interface such as: torsional stiffness (around 20.5 N m rad−1), shear modulus (around 240 MPa), maximal torsional loading (around 0.056 N.m), mode III fracture energy (around 77.5 N m−1) and stress intensity factor (0.27 MPa m1/2).This study paves the way for the use of mode III cleavage testing for the investigation of torsional loading strength of the bone–implant interface, which might help for the development and optimization of implant biomaterial, surface treatment and medical treatment investigations.

Can enoxaparin prevent arthrofibrosis?

Sir, – Enoxaparin as a low molecular weight heparin (LMWH) is able to inhibit the platelet function, increase the microvas-cular permeability, interfere with the interac -tion between platelets and vessel walls, and decrease inflammatory cells, fibroblasts, and growth factors [1, 2]. In addition, it has pre-viously been stated by several investigators that it prevents the post-surgical intraperito-neal adhesion and also minimizes the hepat-ic, cardiac and retina fibrosis [3, 4, 5, 6, 7].The present study was designed for the first time to investigate the therapeutic ef-fects of enoxaparin on the intra-articular fibrosis, a serious complication in modern orthopedic surgery. The study was approved by the local ethics committee of our faculty, in accordance with the ethics standards of “Principles of Laboratory Animal Care”.Arthrofibrosis was induced in both knee joints of 20 mature male rabbits by transect-ing the anterior cruciate ligament under in-tramuscular anesthesia with ketamine and xylazine. Enoxaparin sodium (Clexane, Sanofi Aventis Pharma, France) was daily injected subcutaneously (2 mg/kg) for 35 days in 10 rabbits and the other remaining 10 animals received physiologic saline in the same way as the control animals. After 12 weeks, the rabbits were anesthetized to remove the stiff joint. The severity of adhe-sion was assessed by modified visual scor-ing system described by Rothkopf et al. [8] and histologic parameters.Four samples were excluded due to sep-tic arthritis and unfortunately a sample was missed; therefore, 18 joints in the control group and 17 in the experimental group were tested.Based on the macroscopic adhesion scores, no significant difference was seen between the experimental and control groups (p-value = 0.279). The mean ± standard de-viation values for the control and experimen-tal group were 1.77 ± 0.73 and 1.41 ± 0.61, respectively. In addition, except the vascular proliferation, other microscopic variables such as the inflammatory cell count, con-nective tissue deposition, cartilage and bone content and adhesion, were not significantly different between the two groups (Table 1). It should be mentioned that no giant cell was seen in the tissue sections of either experi-mental or control animals.Enoxaparin has been shown to have both anti-inflammatory and antifibrotic activities in addition to its well-known an-ticoagulant activity. Ergul et al. [9] stated that the fibrinolytic effect of LMWHs could be due to its serine esterase activ-ity. It has been reported that enoxaparin decreased the extent of fibrosis by 36% in liver suggesting its antithrombotic effect as an important role in preventing fibro-sis progression [10]. In addition, Abe et al. [4] stated that the mechanism of anti-fibrotic effects of dalteparin most likely involve down-regulation of transforming growth factor β1.However, the results of some other in-vestigators demonstrated that LMWHs is not effective in reducing fibrosis and adhe-sion formation. Laxer et al. [11] showed that enoxaparin did not ameliorate bleomycin-induced lung fibrosis in mice. Moreover, it has been shown that enoxaparin improved the intestinal wound healing in rat [12] that is opposite to its antifibrotic effect.Subjectively LMWHs was able to reduce arthrofibrosis, but the findings of the present study showed that it is not an effective anti-arthrofibrotic agent. The only variable with significant difference was vascular prolifer-ation; however, vascular proliferation is not a worthy variable in comparison to others. Therefore, we dispense with its significant difference.

Bone adhesives for trauma surgery: A review of challenges and developments

The idea of being able to glue bone fragments with a suitable biocompatible adhesive remains highly attractive to orthopaedic surgeons. Yet despite decades of research, no suitable system that fully meets all the many requirements for such an adhesive has yet been identified. This article reviews the requirements and challenges of developing a bone adhesive for fracture repair and also the substantial progress that has been made. Developments in bone adhesives can roughly be classified into two groups: synthetic and biologically-derived/inspired. Early examples of synthetic adhesives include poly(methyl methacrylate) and related polymers, cyanoacrylates and polyurethanes. These materials are characterised by relatively good mechanical properties but often lack the required biocompatibility and biodegradability. More recent adhesive systems based on lactide–methacrylate chemistry therefore attempt to address these issues. Similarly, there is renewed interest in glass ionomer cements and calcium/magnesium phosphate cements. Biological adhesives include fibrin and gelatin-based systems. These have good biocompatibility and biodegradability but lack the cohesive strength to have good adhesion to bone and are used chiefly in soft tissue applications. Newer examples that are looking more promising include adhesives inspired by mussel adhesive proteins and the “sandcastle glue” of the marine worm Phragmatopoma californica. As well as the challenge to develop the adhesive systems themselves a further need is for greater consistency in the testing of adhesion to bone both in vitro/ex vivo and in vivo. Test methods in the literature are reviewed together with considerations for the design of such tests.

Suppression of the PI3K—Akt pathway is involved in the decreased adhesion and migration of bone marrow‐derived mesenchymal stem cells from non‐obese diabetic mice

Volume 35 (2011), pp. 961–966 Correspondence may be addressed to either Aiming Sang or Zhifeng Gu (email sangam@ntu.edu.cn or guzhifeng@126.com).

Reactive calcium-phosphate-containing poly(ester-co-ether) methacrylate bone adhesives: setting, degradation and drug release considerations

This study has investigated novel bone adhesives consisting of fluid photo-polymerizable poly(lactide-co-propylene glycol-co-lactide)dimethacrylate (PGLA-DMA) mixed with systematically varying fillers of β-tricalcium phosphate (β-TCP) and monocalcium phosphate monohydrate (MCPM), for the delivery of an antibacterial drug chlorhexidine (CHX). All formulations were found to polymerize fully within 200 s after exposure to blue light. In addition, water sorption by the polymerized materials catalyzed varying filler conversion to dicalcium phosphate (DCP) (i.e. brushite and monetite). With greater DCP levels, faster degradation was observed. Moreover, increase in total filler content enhanced CHX release, associated with higher antibacterial activity. These findings thus suggest that such rapid-setting and degradable adhesives with controllable drug delivery property could have potential clinical value as bone adhesives with antibacterial activity.

Cell attachment and response to photocured, degradable bone adhesives containing tricalcium phosphate and purmorphamine

The aim of this study was to quantify and provide evidence as to how addition of tricalcium phosphate (β-TCP) and the Hedgehog agonist purmorphamine to a degradable bone adhesive affects cell attachment/proliferation and Hedgehog pathway activation. Fourier transform infrared spectroscopy demonstrated that high levels (75 wt.%) of β-TCP addition reduced the photocure rate of the chosen poly(propylene glycol–co-lactide) dimethacrylate (PPLM) bone adhesive, but this problem was overcome by increased light exposure. In phosphate-buffered saline the total surface mass loss of set 15 mm diameter PPLM films was ∼3.2 mg in 12 weeks, irrespective of thickness (200 or 400 μm) or β-TCP level (50 or 75 wt.%). With 400 μm samples there was additional bulk material loss. Proliferation of pre-osteoblast cells (MC3T3-E1) on the set adhesive surfaces was enhanced by decreased sample thickness or filler content increase. Degradation evidence suggested that both effects were due to reduced acidic polymeric degradation products. Activation of the Hedgehog pathway was quantified by measuring Gli expression in Light II reporter cells. The 0.01 and 0.1 wt.% purmorphamine in composite discs (400 μm, 75 wt.% β-TCP) enhanced Gli expression of attached cells 2- and 5-fold, respectively, without influencing their number. Pre-storage of the composite samples in culture medium had no detrimental effect on this response. Furthermore, sample storage medium gave no enhanced Gli expression in cells on tissue culture plastic. This suggests drug release levels were very low. Purmorphamine and β-TCP incorporation in PPLM adhesives might, therefore, provide prolonged enhancement of in vivo bone repair without systemic drug side-effects.

Development of apatite coatings on Ti–6Al–7Nb dental implants by biomimetic process and EPD: in vivo studies

This paper compares the results of the effects of a biomimetic coating and electrophoretic deposition (EPD) of hydroxyapatite (HA) on the bond strength between the bone, implant and cell compatibility of Ti–6Al–7Nb dental implants. In the biomimetic process, screw shaped implants were chemically etched and NaOH activated to form hydroxycarbonated apatite after they were soaked for six days in a solution that was five times more concentrated than regular simulated body fluid (SBF). Electrophoretic deposition was also used to obtain a uniform coating of HA on other batchs of screws. Elemental, structural and in vivo histological and biomechanical investigations were carried out on the modified surfaces of the screws. The results show that there was a faster reaction of bone towards the coated implants compared to the uncoated one. More mature bones were observed on HA coated implants and increased mechanical strength (torque value) of bone–implant interface. Higher torque was needed to remove elephoretically and biomimetically HA coated screws from its bed compared to that needed for uncoated one (55, 50·16 and 37·45 N cm respectively). Biomimetic and electrophoretic coating with a bioactive HA leads to high integration between bone and implant by increasing the bioactivity of the product and to promoting mechanical properties of the implanted screws and enhanced osseointegration during the healing period. Owing to the higher roughness and porosity of the EPD coated screws (average Ra = 2921±100 nm), the bone growth was much higher than that coated biomimetically (average Ra = 1550±88 nm). Out of the two methods tried to form bioactive surface, EPD yields high bone adhesion when compared to the biomimetic coating.