Mathematical modelling of the degradation behaviour of biodegradable metals

A mathematical model for the biodegradation of magnesium is developed in this study to inspect the corrosion behaviour of biodegradable implants. The aim of this study was to provide a suitable framework for the assessment of the corrosion rate of magnesium which includes the process of formation/dissolution of the protective film. The model is intended to aid the design of implants with suitable geometries. The level-set method is used to follow the changing geometry of the implants during the corrosion process. A system of partial differential equations is formulated based on the physical and chemical processes that occur at the implant-medium boundary in order to simulate the effect of the formation of a protective film on the degradation rate. The experimental data from the literature on the corrosion of a high-purity magnesium sample immersed in simulated body fluid is used to calibrate the model. The model is then used to predict the degradation behaviour of a porous orthopaedic implant. The model successfully reproduces the precipitation of the corrosion products on the magnesium surface and the effect on the degradation rate. It can be used to simulate the implant degradation and the formation of the corrosion products on the surface of biodegradable magnesium implants with complex geometries.     

LOC103691336/miR-138-5p/BMPR2 axis modulates Mg-mediated osteogenic differentiation in rat femoral fracture model and rat primary bone marrow stromal cells

Intramedullary stabilization is frequently used to treat long bone fractures. Since implant removal can become technically very challenging with the potential to cause further tissue damage, biodegradable materials are emerging as alternative options. Magnesium (Mg)-based biodegradable implants have a controllable degradation rate and good tissue compatibility, which makes them attractive for musculoskeletal research. Herein, the degradation of Mg and steel implants, the pathological characteristics and osteoblast differentiation in mice femora were examined. To investigate the molecular mechanism, we analyzed the differentially expressed long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in Mg-implanted or stain-steel-implanted callus tissues. lncRNA LOC103691336 was upregulated in Mg-implanted tissues and most relevant to BMPR2, a kinase receptor of BMPs with an established role in osteogenesis. The knockdown of LOC103691336 attenuated Mg-mediated osteogenic differentiation. Furthermore, miR-138-5p, previously reported to inhibit osteogenic differentiation, could bind to LOC103691336 and BMPR2 in bone marrow stromal cells (BMSCs). LOC103691336 competed with BMPR2 for miR-138-5p binding in BMSCs to attenuate the inhibitory effect of miR-138-5p on BMPR2 expression. Finally, the effect of LOC103691336 knockdown on Mg-mediated osteogenic differentiation could be attenuated by miR-138-5p inhibition. In conclusion, we provided a novel mechanism of Mg implants mediating the osteogenesis differentiation and demonstrated that Mg implants may be promising for improving fracture healing.     

Kinetics of chondrocyte growth in cell-polymer implants

In vitro cultivation of cartilage cells (chondrocytes) on biodegradable polyglycolic acid (PGA) scaffolds resulted in implants which could potentially be used to repair damaged joint cartilage or for reconstructive surgery. Cell growth kinetics were studied to define conditions under which the cellularity of implants made from isolated calf chondrocytes reached that of the parent calf cartilage. In static cultures, condrocyte growth rates decreased as either implant thickness or implant cell density increased. Over 4 weeks of cultivation, implant permeability to glucose decreased to 3% that of the plain polymer scaffold; this effect was attributed to the decrease in effective implant porosity associated with cartilage tissue regeneration.In a well-mixed culture, implants 1 cm in diameter by 0.3 cm thick maintained high cell growth rates over 7 weeks and hard normal cell densities. Regenerated cartilage with these dimensions is large enough to resurface small joints such as the trapezium bone at the base of the human thumb. Such implants could not be grown statically, since cell growth stopped at 3-4 weeks and cell densities remained below normal. Optimization of the tissue culture environment is thus essential in order to cultivate clinically useful cartilage implants in vitro. (c) 1994 John Wiley & Sons, Inc.     

Revolutionizing orthopaedic biomaterials: The potential of biodegradable and bioresorbable magnesium-based materials for functional tissue engineering

In recent years, there has been a surge of interest in magnesium (Mg) and its alloys as biomaterials for orthopaedic applications, as they possess desirable mechanical properties, good biocompatibility, and biodegradability. Also shown to be osteoinductive, Mg-based materials could be particularly advantageous in functional tissue engineering to improve healing and serve as scaffolds for delivery of drugs, cells, and cytokines. In this paper, we will present two examples of Mg-based orthopaedic devices: an interference screw to accelerate ACL graft healing and a ring to aid in the healing of an injured ACL.     

Soft and hard tissue response to zirconium dioxide dental implants--a clinical study in man

Titanium dental implants have been used successfully in implantology for more than 40 years. Recent research, however, suggests that titanium might have more side effects than previously believed. Zirconia ceramics have been employed in orthopaedic surgery for approximately 30 years and were recently introduced into dentistry as a metal replacement for crown and bridge work as well as implant abutments. Zirconium dioxide has been shown in both in vitro and in vivo studies to have desirable osseointegrative properties. This clinical study shows that dental implants made from zirconia are a feasible alternative to titanium dental implants. In addition to excellent cosmetic results, zirconia implants allow a degree of osseointegration and soft tissue response that is superior to titanium dental implants.     

Biomechanical validation of finite element models for two silicone metacarpophalangeal joint implants

Silicone implants are used for prosthetic arthroplasty of metacarpophalangeal (MCP) joints severely damaged by rheumatoid arthritis. Different silicone elastomer MCP implant designs have been developed, including the Swanson and the NeuFlex implants. The goal of this study was to compare the in vitro mechanical behavior of Swanson and NeuFlex MCP joint implants. Three-dimensional (3D) finite element (FE) models of the silicone implants were modeled using the commercial software ANSYS and subjected to angular displacement from 0 deg to 90 deg. FE models were validated using mechanical tests of implants incrementally bent from 0 deg to 90 deg in a joint simulator. Swanson size 2 and 4 implants were compared with NeuFlex size 10 and 30 implants, respectively. Good agreement was observed throughout the range of motion for the flexion bending moment derived from 3D FE models and mechanical tests. From 30 deg to 90 deg, the Swanson 2 demonstrated a greater resistance to deformation than the NeuFlex 10 and required a greater bending moment for joint flexion. For larger implant sizes, the NeuFlex 30 had a steeper moment-displacement curve, but required a lower moment than the Swanson 4, due to implant preflexion. On average, the stress generated at the implant hinge from 30 deg to 90 deg was lower in the NeuFlex than in the Swanson. On average, starting from the neutral position of 30 deg for the preflexed NeuFlex implant, higher moments were required to extend the NeuFlex implants to 0 deg compared with the Swanson implants, which returned spontaneously to resting position. Implant toggling within the medullary canals was less in the NeuFlex than in the Swanson. The differential performance of these implants may be useful in implant selection based on the preoperative condition(s) of the joint and specific patient functional needs.     

Blood and plasma titanium levels associated with well-functioning hip implants

BackgroundHip implants are usually manufactured from cobalt-chromium and titanium alloys. As the implants wear and corrode, metal debris is released into the surrounding tissue and blood, providing a potential biomarker for their function. Whilst there are laboratory reference levels for blood cobalt and chromium in patients with well and poorly functioning hip implants, there are no such guidelines for titanium. This is despite the increasing use of titanium implants worldwide.Patients and methodsWe recruited a consecutive series of 95 patients (mean age 71 years, mean time after surgery 8.5 years) with one hip implant type, inserted by the same surgeon. We assessed clinical and radiological outcome, and measured blood and plasma titanium using high resolution inductively-coupled plasma mass spectrometry.ResultsThe upper normal reference limit for blood and plasma titanium was 2.20 and 2.56 μg L⁻¹, respectively, and did not differ significantly between males and females.ConclusionWe are the first to propose a laboratory reference level for blood and plasma titanium in patients with well-functioning titanium hip implants. This is an essential starting point for further studies to explore the clinical usefulness of blood titanium as a biomarker of orthopaedic implant performance, and comes at a time of considerable controversy regarding the use of certain titanium alloys in hip arthroplasty.     

Nanotopographical control of human osteoprogenitor differentiation

Current load-bearing orthopaedic implants are produced in 'bio-inert' materials such as titanium alloys. When inserted into the reamed bone during hip or knee replacement surgery the implants interact with mesenchymal populations including the bone marrow. Bio-inert materials are shielded from the body by differentiation of the cells along the fibroblastic lineage producing scar tissue and inferior healing. This is exacerbated by implant micromotion, which can lead to capsule formation. Thus, next-generation implant materials will have to elicit influence over osteoprogenitor differentiation and mesenchymal populations in order to recruit osteoblastic cells and produce direct bone apposition onto the implant. A powerful method of delivering cues to cells is via topography. Micro-scale topography has been shown to affect cell adhesion, migration, cytoskeleton, proliferation and differentiation of a large range of cell types (thus far all cell types tested have been shown to be responsive to topographical cues). More recent research with nanotopography has also shown a broad range of cell response, with fibroblastic cells sensing down to 10 nm in height. Initial studies with human mesenchymal populations and osteoprogenitor populations have again shown strong cell responses to nanofeatures with increased levels of osteocalcin and osteopontin production from the cells on certain topographies. This is indicative of increased osteoblastic activity on the nanotextured materials. Looking at preliminary data, it is tempting to speculate that progenitor cells are, in fact, more responsive to topography than more mature cell types and that they are actively seeking cues from their environment. This review will investigate the range of nanotopographies available to researchers and our present understanding of mechanisms of progenitor cell response. Finally, it will make some speculations of the future of nanomaterials and progenitor cells in tissue engineering.     

Variability in the properties of silicone gel breast implants.

Several generations of silicone gel breast implants have been produced by implant manufacturers. The primary material usually viewed as the base material in the manufacture of implants is polydimethylsiloxane. Polymeric reactions are notorious for their variability and nonuniformity. The elastomer used in different types of implants can have vastly different properties. Furthermore, the material properties associated with a particular type of implant can vary considerably from one lot to the next. Considering the various designs, styles, and manufacturing techniques associated with silicone gel implants, knowledge of the original properties of the implants before implantation is important in determining the effects of aging in vivo. This study was conducted to investigate differences in key mechanical and chemical properties of silicone gel breast implant materials. The two types of implants chosen for analysis were Silastic I and Silastic II control implants. Material property data were determined for both types of controls and significant differences were found in their values. Lot-to-lot variability was also investigated and found to be significant.     

The management of anterior chest wall deformity in patients presenting for breast augmentation

Anterior chest wall asymmetry is sometimes encountered in patients presenting for consideration of breast augmentation. The chest wall asymmetry or deficiency may be significant enough to consider reconstruction at the same time as breast augmentation in a small number of cases. Customized and prefabricated chest wall implants have been used in a variety of conditions including Poland syndrome, pectus excavatum, and sunken anterior chest. Careful moulage preparation and on-table implant modification are needed to "seat" these implants on the skeletal chest wall under the pectoralis major muscle. The chest wall implant provides a base for the subsequent breast prostheses and fills up a bony deficit that cannot be camouflaged by the breast prostheses alone.     

Sustained release implants of chloroquine phosphate for possible use in chemoprophylaxis of malaria

Implants of chloroquine phosphate (CQP) using biodegradable polymer, gelatin (G) and cross-linked gelatin (CLG) were prepared and evaluated to assess their physicochemical properties and in vitro release profile. The mechanism and kinetics of release were studied to correlate the release phenomenon with the formulation parameters. Out of many batches of the implants investigated, the implant prepared with 20% gelatin at 2:1 drug polymer ratio, 10% crosslinking agent and 2% plasticizer (Batch J) was found to provide optimum release behavior conforming to the requirements of a long term implant for a week. In vivo studies conducted on albino rats showed consistent therapeutic blood level over a period of 7 days. Mean residence time (MRT) of the drug released in the body, calculated as the ratio of the area under the first moment curve (AUMC) to area under concentration time curve (AUC) was 72 hr for implant against 2.42 hr for subcutaneous injection.     

Orthopaedic Implant as Drug Delivery System: a Numerical Approach

Abstract

There is a current trend to propose cementless total joint arthroplasty (TJA) to younger patients. These patients have more demanding physical activity resulting in an increased failure rate of the implants. In particular for these type of patients, the desired service life of the implant should be extended. The actual implant used do not fulfil this requirement.

In this study, a new concept of orthopaedic implant is presented where the implant is not only a structural support but also a local drug delivery system. The delivered drug is meant to influence the bone remodeling in a way so as to compensate the effects of peri-implant osteolysis. To test this concept, we extended an existing bone remodeling model to include the effect of a drug. The results show that a more homogeneous bone density distribution can be obtained around the implant. Implants used as drug delivery systems could then be an alternative way to increase implant service life.     

Surface Modification of Biodegradable Mg-4Zn Alloy Using PMEDM: An Experimental Investigation,Optimization and Corrosion Analysis

ObjectivesMagnesium alloys are the potential candidate for metallic implants due to their excellent mechanical characteristics, biodegradable nature, and properties similar to human bone. However, a high degradation rate is primary obstacle in implementing these alloys as biodegradable orthopedic implants. Powder-mixed electric discharge machining (PMEDM) is an emerging method of surface modification of metallic alloys that can be implemented to improve the corrosion resistance of Mg alloys. Therefore, PMEDM using zirconium (Zr) and manganese (Mn) powder particles has been proposed to modify the surface characteristics of Mg-4Zn alloy.Materials and MethodsIn the present work, Zr and Mn powders have been used in varying concentrations during PMEDM of Mg-4Zn alloy. Experiments were conducted as per mixed design L18 orthogonal array (OA). Taguchi and Grey Relational Analysis (GRA) have been used to optimize the process parameters. Analysis of response characteristics, namely material removal rate (MRR), surface roughness (SR), and thickness of the alloyed layer (TAL), has been carried out at different values of input variables (like powder additives (P_a), powder concentration (C_p), peak current (I_p), pulse on time (T_on) and duty cycle (DC)). The corrosion analysis was carried out by immersing the specimen (machined at an optimized setting) in simulated body fluid (SBF).ResultsIt is observed from the analysis that C_p, I_p, and T_on play a pivotal role in evaluating response characteristics. The favorable setting suggested by the gray approach is P_a: Zr; C_p: 2 g/l; I_p: 4A; T_on: 50 μs; DC: 80%, while responses at this setting are confirmed by confirmation experiments with MRR: 32.14 mm³/min; SR: 5.578 μm and TAL: 8.28 μm. The immersion test signifies that the corrosion rate (CR) of PMEDMed sample (3.20 mm/year) is 40.74% lesser than the corrosion rate of polished sample (5.40 mm/year).ConclusionZr powder shows better performance in terms of higher MRR, lower SR and higher TAL as compared to Mn powder during the PMEDM process. The corroded surface of polished sample exhibited larger size micro pits and cracks than the machined sample, which concluded that surface modification of MZ-4Zn alloy via PMEDM is a powerful tool to enhance its corrosion resistance.     

Bone grafts impregnated with antibiotics as a tool for treating infected implants in orthopedic surgery – one stage revision results

Infection of an orthopedic implant is considered a devastating complication, necessitating its complete removal and thorough debridement of the site. Osseous defects are common in such conditions and need to be addressed before a new implant may be inserted. So far bone grafting has been contraindicated in bacterially contaminated areas and could only be performed as soon as all signs of infection have ceased. Usually long term antibiotic treatment and a multitude of surgical interventions within a period of several months is required until a definitive supply can be achieved. Allograft bone may be impregnated with high loads of antibiotics using special incubation techniques. Based on this technology 48 exchange procedures of infected orthopaedic implants were performed in a single stage, all of them without the use of bone cement. There were 37 infected hips, 8 knees and 3 infected osteosyntheses. Two hips required re-revision because of persisting infection, the remaining 46 patients stayed infect free for a period between 1 and 7 years after surgery. No adverse side effects could be found. Incorporation appeared as after grafting with unimpregnated bone grafts. Antibiotic loaded allograft bone is a powerful tool in septic revision surgery, enabling restoration of bone stock, insertion of a new implant and control of infection in a single operation.     

Biomedical applications of degradable polyphosphazenes

This article describes the synthesis of biodegradable polyphosphazenes. The rate of degradation can be varied in a controllable manner by the introduction of hydrolysis-sensitive amino acid ester side groups or by blending of polymers. Biodegradable polyphosphazenes can be used for the preparation of drug-containing implants and this is illustrated for devices containing the cytostatic agent mitomycin C. This article reviews data about the degradation characteristics of poly[(amino acid ester)phosphazene] derivatives that have been discussed previously. Some new data about MMC-containing poly[(organo)phosphazene] devices are discussed as well. (c) 1996 John Wiley & Sons, Inc.     

Worldwide Enucleation Techniques and Materials for Treatment of Retinoblastoma: An International Survey

Purpose

To investigate the current practice of enucleation with or without orbital implant for retinoblastoma in countries across the world.

Methods

A digital survey identifying operation techniques and material used for orbital implants after enucleation in patients with retinoblastoma.

Results

We received a response of 58 surgeons in 32 different countries. A primary artificial implant is routinely inserted by 42 (72.4%) surgeons. Ten (17.2%) surgeons leave the socket empty, three (5.2%) decide per case. Other surgeons insert a dermis fat graft as a standard primary implant (n=1), or fill the socket in a standard secondary procedure (n=2; one uses dermis fat grafts and one artificial implants). The choice for porous implants was more frequent than for non-porous implants: 27 (58.7%) and 15 (32.6%), respectively. Both porous and non-porous implant types are used by 4 (8.7%) surgeons. Twenty-five surgeons (54.3%) insert bare implants, 11 (23.9%) use separate wrappings, eight (17.4%) use implants with prefab wrapping and two insert implants with and without wrapping depending on type of implant. Attachment of the muscles to the wrapping or implant (at various locations) is done by 31 (53.4%) surgeons. Eleven (19.0%) use a myoconjunctival technique, nine (15.5%) suture the muscles to each other and seven (12.1%) do not reattach the muscles. Measures to improve volume are implant exchange at an older age (n=4), the use of Restylane SQ (n=1) and osmotic expanders (n=1). Pegging is done by two surgeons.

Conclusion

No (worldwide) consensus exists about the use of material and techniques for enucleation for the treatment of retinoblastoma. Considerations for the use of different techniques are discussed.     

A paradigm for the development and evaluation of novel implant topologies for bone fixation: Implant design and fabrication

The future development of bio-integrated devices will improve the functionality of robotic prosthetic limbs. A critical step in the advancement of bio-integrated prostheses will be establishing long-term, secure fixation to the remnant bone. To overcome limitations associated with contemporary bone-anchored prosthetic limbs, we established a paradigm for developing and fabricating novel orthopedic implants undergoing specified loading. A topology optimization scheme was utilized to generate optimal implant macrostructures that minimize deformations near the bone-implant interface. Variations in implant characteristics and interfacial connectivity were investigated to examine how these variables influence the layout of the optimized implant. For enhanced tissue integration, the optimally designed macroscopic geometry of a titanium (Ti)-alloy implant was further modified by introducing optimized microstructures. The complex geometries of selected implants were successfully fabricated using selective laser sintering (SLS) technology. Fabrication accuracy was assessed by comparing volumes and cross-sectional areas of fabricated implants to CAD data. The error of fabricated volume to CAD design volume was less than 8% and differences in cross sectional areas between SEM images of fabricated implants and corresponding cross sections from CAD design were on average less than 9%. We have demonstrated that this computational design method, combined with solid freeform fabrication techniques, provides a versatile way to develop novel orthopedic implants.     

Subfascial breast implant: a new procedure

Breast augmentation techniques using the submuscular and subglandular planes to introduce the implant are well known and widely used procedures. The authors have been using the subfascial dissection plane, a new concept for breast augmentation. From October of 1998 to September of 2001, 263 patients underwent breast augmentation. In all cases, the implants were inserted into the subfascial plane. McGhan 410 anatomic biodimensional, cohesive gel implants (size, 155 to 310 g) were used. There are additional benefits using this technique; these include avoiding implant deformation or distortion (as seen in the retromuscular position), leaving additional soft tissue between the implant and the skin, and minimizing implant edge prominence (inherent to retroglandular placement). These technical details lead to fewer patient complaints. Morbidity is similar to that of other techniques.     

Hybrid titanium/biodegradable polymer implants with an hierarchical pore structure as a means to control selective cell movement

In order to improve implant success rate, it is important to enhance their responsiveness to the prevailing conditions following implantation. Uncontrolled movement of inflammatory cells and fibroblasts is one of these in vivo problems and the porosity properties of the implant have a strong effect on these. Here, we describe a hybrid system composed of a macroporous titanium structure filled with a microporous biodegradable polymer. This polymer matrix has a distinct porosity gradient to accommodate different cell types (fibroblasts and epithelial cells). The main clinical application of this system will be the prevention of restenosis due to excessive fibroblast migration and proliferation in the case of tracheal implants. METHODOLOGY/PRINCIPAL FINDINGS: A microbead-based titanium template was filled with a porous Poly (L-lactic acid) (PLLA) body by freeze-extraction method. A distinct porosity difference was obtained between the inner and outer surfaces of the implant as characterized by image analysis and Mercury porosimetry (9.8±2.2 μm vs. 36.7±11.4 μm, p≤0.05). On top, a thin PLLA film was added to optimize the growth of epithelial cells, which was confirmed by using human respiratory epithelial cells. To check the control of fibroblast movement, PKH26 labeled fibroblasts were seeded onto Titanium and Titanium/PLLA implants. The cell movement was quantified by confocal microscopy: in one week cells moved deeper in Ti samples compared to Ti/PLLA. CONCLUSIONS: In vitro experiments showed that this new implant is effective for guiding different kind of cells it will contact upon implantation. Overall, this system would enable spatial and temporal control over cell migration by a gradient ranging from macroporosity to nanoporosity within a tracheal implant. Moreover, mechanical properties will be dependent mainly on the titanium frame. This will make it possible to create a polymeric environment which is suitable for cells without the need to meet mechanical requirements with the polymeric structure.