Polymeric Implants Research Articles

Short- and long-term results of orbital floor fractures treatment

The objective of this research was to study complications of orbital floor reconstruction by making analysis of early and late follow up treatment results of patients with orbital floor fractures. We summerized the experience in surgery of 215 victims with zygomatico-orbital complex fractures, who underwent treatment in teaching hospitals of the oral and maxillo-facial surgery department of Privolzhsky Research Medical University from 2011 to 2017. The orbital wall fractures which required reconstruction and restorative treatment were diagnosed in 78 (36.3%) patients. The amount of surgical intervention included transconjuctive approach and orbital floor reconstruction with polymeric and metal implants. In most cases we obtained good and satisfactory results during the period of early and late follow up. We made the analysis of developed early and late complications from orbital floor reconstruction. Post-operative enophthalmos and implant displacement are noted to be the most adverse events in the late follow up period and they require re-surgery. Our experience suggests that it is possible to avoid complications and receive good esthetic and functional results in case a surgeon is highly qualified and carefully plans an operation, namely calculation of anatomical and topometrical orbit parameters by CT and a right choice of operation methods and implants.

Effects of wear particles of polyether-ether-ketone and cobalt-chromium-molybdenum on CD4- and CD8-T-cell responses.

T-cells, second only to macrophages, are often considered as the potential cells involved in debris-related failure of arthroplasty. Here, we assessed the effects of particulate wear debris on T-cells and inflammatory reactions. Blood samples from 25 donors were incubated with polyether-ether-ketone (PEEK) and cobalt-chromium-molybdenum (CoCrMo) particles generated by custom cryo-milling and pulverization. The T-cell phenotypes were assessed using immunostaining and flow cytometry. For the in vivo study, 0.1 mL of each particle suspension (approximately 1.0 × 108 wear particles) was injected into murine knee joints; the synovium and spleen were collected one week after the operation for histological examination and immunofluorescence staining. The T-cell responses observed included low-level activation of Th1, Th2, Th17, and CD8+ pathways after 72 h of co-culture of the particles with peripheral blood mononuclear cells. Obvious CD8+ T-cell responses were observed in local synovium and peripheral spleen, with higher inflammatory cytokine expression in the CoCrMo group. Relatively minor cytotoxic and immunological reactions were observed in vitro, with PEEK and CoCrMo particle-induced immune responses being primarily mediated by CD8+ T-cells, rather than CD4+ T-cells, in vivo. Overall, PEEK wear particles induced fewer inflammatory reactions than CoCrMo particles. This study verified that PEEK was suitable as a potential alternative for metals in total knee replacements in terms of the immunological reaction to PEEK particles, and shed light on the effects of wear particles from polymer and metal-based implants on immune responses.

A Preliminary Comparison Suggests Poor Performance of Carbon Fiber Reinforced Versus Titanium Plates in Distal Femoral Osteotomy.

Carbon fiber-reinforced (CFR) polymer implants have theoretical advantages over titanium plates. The aim of the present study was to assess our early outcomes with CFR plates in lateral opening-wedge distal femoral osteotomy to correct valgus lower limb malalignment. We asked the following: (1) Did the CFR polymer implant change time to union when compared with the titanium implant? (2) Did the incidence of displacement of medial cortical fractures differ between the implants? (3) Did the incidence of complications differ between the two techniques, and did other factors, such as bone graft material used, affect healing? A retrospective review of 16 limbs treated with an opening-wedge distal femoral osteotomy for genu valgum using either titanium (n=10) or CFR plates (n=6) was performed. Patient and clinical covariates as well as the primary outcome of time to union and secondary outcome of fracture displacement were collected and analyzed. Those treated with CFR plates had longer times to union than did those in the titanium-treated group (median, 121.5 vs 81.5days, respectively). The incidence of fracture displacement was higher in the CFR plate-treated group (CFR, n=5/6; titanium, n=1/10). Although the CFR plate-treated group had a 33% nonunion incidence while the titanium group had no nonunions, the study lacked the power to show significance. Bone graft material used did not affect outcome. Complication rates were higher in the CFR plate-treated patients. The CFR plate was associated with a longer time to unite and higher fracture displacement rate than the titanium plate. As this is a retrospective case series, further research is required to confirm these results and clarify best practices in plating of distal femoral osteotomy for deformity correction.

Customized cranial implant manufactured by incremental sheet forming using a biocompatible polymer

PurposeThe purpose of this paper is to demonstrate the feasibility of incremental sheet forming (ISF), using the most common variants, single-point incremental forming (SPIF) and two-point incremental forming (TPIF), to produce prototypes of customized cranial implants using a biocompatible polymer (ultrahigh molecular weight polyethylene, UHMWPE), ensuring an appropriate geometric accuracy and cost.Design/methodology/approachThe cranial implant is designed based on computerized tomographies (CT) of the patient, converting them into a 3D model using the software InVesalius. To generate the toolpath for the forming operation computer-aided manufacturing (CAM) software is used. Once the cranial implant is manufactured, a 3D scanning system is used to determine the geometric deviation between the real part and the initial design.FindingsThe results corroborate that it is possible to successfully manufacture a customized cranial implant using ISF, being able to improve the geometric accuracy using the TPIF variant with a negative die.Originality/valueThis paper is one of the first research works in which a customized cranial implant is successfully manufactured using a flexible technology, ISF and a biocompatible polymer. The use of polymeric implants in cranioplasty is advantageous because of their lightweight, low heat conductivity and mechanical properties similar to bone. Furthermore, the cost of the implant has been calculated considering not only the raw materials and manufacturing time but also the environmental impact, revealing that it is a cheap process with a low lead-time.

Biodegradable Polymeric Injectable Implants for Long-Term Delivery of Contraceptive Drugs.

Development of injectable, long-lasting, contraceptive drug delivery formulations and implants are highly desired to avoid unplanned pregnancies while improving patient compliance and reducing adverse side effects and treatment costs. The present study reports on the fabrication and characterization of two levonorgestrel (LNG) microsphere injectable formulations. Poly(ε-caprolactone) (PCL) with 12.5% and 24% (w/w) LNG were fabricated into microspheres, measuring 300±125 μm, via the oil-in-water (o/w) emulsion solvent evaporation technique. Formulations showed sustained drug release up to 120 days. FTIR, XRD, DSC, and TGA confirmed the absence of LNG chemical interaction with PCL as well as its molecular level distribution. The in vitro release of LNG was calculated to be Fickian diffusion controlled and properly characterized. The inclusion of multiple elevated release temperatures allowed for the application of the Arrhenius model to calculate drug release constants and representative sampling intervals, demonstrating the use of elevated temperatures for accelerated-time drug release studies.

Development of a goat model for evaluation of withaferin A: Cervical implants for the treatment of cervical intraepithelial neoplasia

Cervical cancer is caused by human papillomavirus (HPV). The disease develops over many years through a series of precancerous lesions. Cervical cancer can be prevented by HPV-vaccination, screening and treatment of precancer before development of cervical cancer. The treatment of high-grade cervical dysplasia (CIN 2+) has traditionally been by cervical conization. Surgical procedures are associated with increased risk of undesirable side effects including bleeding, infection, scarring (stenosis), infertility and complications in later pregnancies. An inexpensive, non-invasive method of delivering therapeutics locally will be favorable to treat precancerous cervical lesions without damaging healthy tissue. The feasibility and safety of a sustained, continuous drug-releasing cervical polymeric implant for use in clinical trials was studied using a large animal model. The goat (Capra hircus), non-pregnant adult female Boer goats, was chosen due to similarities in cervical dimensions to the human. Estrus was induced with progesterone CIDR® vaginal implants for 14days followed by the administration of chorionic gonadotropins 48h prior to removal of the progesterone implants to relax the cervix to allow for the placement of the cervical implant. Cervical implants, containing 2% and 4% withaferin A (WFA), with 8 coats of blank polymer, provided sustained release for a long duration and were used for the animal study. The ‘mushroom’-shaped cervical polymeric implant, originally designed for women required redesigning to be accommodated within the goat cervix. The cervical implants were well tolerated by the animals with no obvious evidence of discomfort, systemic or local inflammation or toxicity. In addition, we developed a new method to analyze tissue WFA levels by solvent extractions and LS/MS-MS. WFA was found to be localized to the target and adjacent tissues with 12–16ng WFA/g tissue, with essentially no detectable WFA in distant tissues. This study suggests that the goat is a good large animal model for the future development and evaluation of therapeutic efficacy of continuous local drug delivery by cervical polymeric implants to treat precancerous cervical lesions.

The development of bioresorbable composite polymeric implants with high mechanical strength.

Implants for the treatment of tissue defects should mimic the mechanical properties of the native tissue of interest and should be resorbable as well as biocompatible. In this work, we developed a scaffold from variants of poly(glycolic) acid which were braided and coated with an elastomer of poly(glycolide-co-caprolactone) and crosslinked. The coating of the scaffold with the elastomer led to higher mechanical strength in terms of compression, expansion and elasticity compared to braids without the elastomer coating. These composite scaffolds were found to have expansion properties similar to metallic stents, utilizing materials which are typically much weaker than metal. We optimized the mechanical properties of the implant by tuning the elastomer branching structure, crosslink density, and molecular weight. The scaffolds were shown to be highly resorbable following implantation in a porcine femoral artery. Biocompatibility was studied in vivo in an ovine model by implanting the scaffolds into femoral arteries. The scaffolds were able to support an expanded open lumen over 12 months in vivo and also fully resorbed by 18 months in the ovine model.

Tacrolimus delivered from polymeric implants suppressed inflammation and angiogenesis in vivo without inducing nephrotoxicity, hepatotoxicity, and myelosuppression

Implants containing tacrolimus and poly(ɛ-caprolactone) (tacrolimus PCL implants) were designed to release the drug directly into the inflammatory and angiogenesis site without inducing systemic toxicity. A non-biocompatible sponge, inserted into the subcutaneous tissue of mice, functioned as a frame for inducing inflammatory and angiogenic responses. After 4 days post-insertion of sponges, PCL implants loaded with tacrolimus were inserted adjacent to the pathological site, and the cellular and molecular components of inflammation were monitored. PCL implants constantly released tacrolimus into the target site. Tacrolimus limited the expression of TNF-α, a pro-angiogenic and pro-inflammatory cytokine. As a result, the neovascularization was inhibited. It also limited the neutrophil migration at the early stage of inflammation and the monocyte/macrophage infiltration at the proliferative phase due to the reduced activities of myeloperoxidase (MPO) and N-Acetyl-β-d-Glucosaminidase (NAG), respectively. Tacrolimus released from PCL implants did not induce toxicity in the liver and kidney, since the biomarkers of functionality of these organs showed normal levels. In addition, the drug did not promote myelosuppression. It was suggested that the controlled tacrolimus release from implantable devices directly into the pathological site could provide the remission of the inflammatory and angiogenic responses without carrying out organ toxicity.

Porous glass-ceramic orbital implants: A feasibility study

Surgical removal of a diseased ocular globe is followed by the placement of a permanent orbital implant in the patient’s anophthalmic cavity to provide adequate support to surrounding tissues. We fabricated foam-like CaSiO3-containing glass-ceramics that exhibited favorable micro-architectural characteristics for use as orbital implant materials, i.e. a network of open and large macropores (∼250 µm) that could potentially allow ingrowth of fibrovascular tissue. The implants had an excellent chemical stability in contact with simulated body fluids (no mass losses were registered after soaking for 1 month in vitro) and high mechanical strength (∼20 MPa under compression) to permit safe manipulation during surgery. Therefore, this new glass-ceramic porous material is a promising, potentially less expensive alternative to existing polymeric or ceramic bioinert orbital implants.

Reconstruction of biological functions: novel implant concepts for cardiovascular, ophthal-mologic and otolaryngologic applications

Abstract Biomedical engineering innovations towards the reconstruction of biological functions seek to improve the quality of patients’ lives. The coordinated research project “RESPONSE – Partnership for Innovation in Implant Technology” (BMBF program Twenty20 – Partnership for Innovation, 2014 - 2021) is focusing on the development of novel concepts for (i) cardiovascular scaffolds, glaucoma and ENT stents, (ii) transcatheter heart valves and venous valves, (iii) polymeric implants and polymer/drug formulations. Current clinical paradigm shifts, fostered by the progress in implant technology and a growing global demand, frame the background for the joint research efforts of academia and industry in the RESPONSE consortium.

Degradation of Polymeric Material used for Osteosynthesis and Comparison of Fracture Toughness between Test and FEA

Biodegradable polymers such as PLA, PGA, PLGA etc., inside the human body often pose a tough challenge for the orthopedic doctors and material scientists. Unlike metallic or ceramic implants, where deterioration of the mechanical properties has never been an issue, biodegradable polymeric implants, used for Osteosynthesis, deteriorate while the fractured bone is subjected to kinesiological stress during healing process. To understand how biodegradable materials lose its mechanical properties, an investigation into the influence of degradation process on Mode-I fracture toughness of poly (lactide-co-glycolide), PLGA 85:15 material was initiated. The objective of this study was to build an improved understanding of the deterioration of biodegradable polymers mechanical properties during in-vitro degradation and how this change may affect long term in-vivo performance of the implants. A simple mathematical relationship was established to understand the change in the Young’s modulus during the degradation process. Compact tension specimens were designed and molded for mode-I fracture criterion and then put in 3% concentrated Hydrogen peroxide (H2O2) to study the degradation process. FEA (Finite Element Analysis) was used to study the change in mechanical properties and then the results were compared with the physical test. Mode-I fracture toughness, KIC was measured and the behavior of the polymer was also identified. It was seen that the fracture toughness, KIC of PLGA 85:15 decreased with the progression of degradation. Finally, it was concluded that an increase in the Young’s modulus made PLGA 85:15 very brittle and hence resulted in reduced fracture toughness.

Impact of the Hydration States of Polymers on Their Hemocompatibility for Medical Applications: A Review.

Water has a key role in the functioning of all biological systems, it mediates many biochemical reactions, as well as other biological activities such as material biocompatibility. Water is often considered as an inert solvent, however at the molecular level, it shows different behavior when sorbed onto surfaces like polymeric implants. Three states of water have been recognized: non-freezable water, which does not freeze even at −100 °C; intermediate water, which freezes below 0 °C; and, free water, which freezes at 0 °C like bulk water. This review describes the different states of water and the techniques for their identification and quantification, and analyzes their relationship with hemocompatibility in polymer surfaces. Intermediate water content higher than 3 wt % is related to better hemocompatibility for poly(ethylene glycol), poly(meth)acrylates, aliphatic carbonyls, and poly(lactic-co-glycolic acid) surfaces. Therefore, characterizing water states in addition to water content is key for polymer selection and material design for medical applications.

Non-destructive and wireless monitoring of biodegradable polymers

A method for monitoring changes in biodegradable polymers during hydrolysis is proposed. This wireless and non-destructive method is based on inductively coupled passive resonance sensors embedded in the polymer shell. In this study, we prepared specimens using two poly(lactide-co-glycolide) copolymers possessing different degradation profiles. The copolymer embedded sensors were immersed in buffer solution and their resonance features were compared with periodically performed conventional polymer characterization methods. A clear difference was noticed in the wirelessly measured signals between the two tested copolymer materials. Also the reference methods showed clear differences between the degradation profiles of the copolymers. The wirelessly measured signals are likely to correlate to the structural changes in the materials during the hydrolysis. In the future, this technique could be used in the laboratory to provide easy-to-access in situ information about the polymers. Even the state of biodegradable polymer implants could be wirelessly monitored.

Plasma immersion ion implantation of polyurethane shape memory polymer: Surface properties and protein immobilization

Polyurethane-type shape memory polymers (SMPU) are promising biomedical implant materials due to their ability to recover to a predetermined shape from a temporary shape induced by thermal activation close to human body temperature and their advantageous mechanical properties including large recovery strains and low recovery stresses. Plasma Immersion Ion Implantation (PIII) is a surface modification process using energetic ions that generates radicals in polymer surfaces leading to carbonisation and oxidation and the ability to covalently immobilise proteins without the need for wet chemistry. Here we show that PIII treatment of SMPU significantly enhances its bioactivity making SMPU suitable for applications in permanent implantable biomedical devices. Scanning Electron Microscopy (SEM), contact angle measurements, surface energy measurements, attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS) were used to characterise the PIII modified surface, including its after treatment aging kinetics and its capability to covalently immobilise protein directly from solution. The results show a substantial improvement in wettability and dramatic changes of surface chemical composition dependent on treatment duration, due to the generation of radicals and subsequent oxidation. The SMPU surface, PIII treated for 200s, achieved a saturated level of covalently immobilized protein indicating that a full monolayer coverage was achieved. We conclude that PIII is a promising and efficient surface modification method to enhance the biocompatibility of SMPU for use in medical applications that demand bioactivity for tissue integration and stability in vivo.

Modifying the surfaces of fluorocarbon polymer implants in the plasma of a high-voltage nanosecond discharge

The possibility in principle is shown for rapidly and efficiently modifying the surface of medical articles made of polytetrafluoroethylene (PTFE) by placing them in a bulk plasma discharge formed in a highly overvoltage gap. As an example, by processing PTFE films with nanosecond discharges at a frequency of 3 kHz over a few seconds, it is possible to substantially improve the conditions for cytoadherence and increase the permeability of an implant, which is an important factor for its integration into adjacent tissues.

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A new approach for the immobilization of poly(acrylic) acid as a chemically reactive cross-linker on the surface of poly(lactic) acid-based biomaterials

A new approach for the immobilization of poly(acrylic) acid (PAA) as a chemically reactive cross-linker on the surface of poly(lactic) acid-based (PLA) biomaterials is described. The proposed technique includes non-covalent attachment of a PAA layer to the surface of PLA-based biomaterial via biomaterial surface treatment with solvent/non-solvent mixture followed by the entrapment of PAA from its solution. Surface morphology and wettability of the obtained PLA-PAA composite materials were investigated by AFM and the sitting drop method respectively. The amount of the carboxyl groups on the composites surface was determined by using the fluorescent compounds (2-(5-aminobenzo[d]oxazol-2-yl)phenol (ABO) and its acyl derivative N-(2-(2-hydroxyphenyl)benzo[d]oxazol-5-yl)acetamide (AcABO)). It was shown that it is possible to obtain PLA-PAA composites with various surface relief and tunable wettability (57°, 62° and 66°). The capacity of the created PAA layer could be varied from 1.5nmol/cm2 to 0.1μmol/cm2 depending on the modification conditions. Additionally, using bovine serum albumin (BSA) it was demonstrated that such composites could be modified with proteins with high binding density (around 0.18nmol/cm2). Obtained fluoro-labeled PLA-PAA materials, as well as PLA-PAA composites themselves, are valuable since they can be used for biodegradable polymer implants tracking in living systems and as drug delivery systems.

Polymeric implant of methylprednisolone for spinal injury: preparation and characterization

Purpose: To improve the effectiveness and reduce the systemic side effects of methylprednisolone in traumatic spinal injuries, its polymeric implants were prepared using chitosan and sodium alginate as the biocompatible polymers. Methods: Implants of methylprednisolone sodium succinate (MPSS) were prepared by molding the drug-loaded polymeric mass obtained after ionotropic gelation method. The prepared implants were evaluated for drug loading, in vitro drug release and in vivo performance in traumatic spinal-injury rat model with paraplegia. Results: All the implant formulations were light pale solid matrix with smooth texture. Implants showed 86.56 ± 2.07 % drug loading. Drug release was 89.29 ± 1.25 % at the end of 7 days. Motor function was evaluated in traumatic spinal injury-induced rats in terms of its movement on the horizontal bar. At the end of 7 days, the test group showed the activity score (4.75 ± 0.02) slightly higher than that of standard (4.62 ± 0.25), but the difference was not statistically different ( p > 0.05). Conclusion: MPSS-loaded implants produces good recovery in traumatic spinal injury rats. Keywords: Spinal injury, Spinal column, Methylprednisolone, Implant, Activity score, Motor function

Assessment of mechanical behavior of PLA composites reinforced with Mg micro-particles through depth-sensing indentations analysis

This work deals with the mechanical characterization by depth-sensing indentation (DSI) of PLLA and PLDA composites reinforced with micro-particles of Mg (up to 15wt%), which is a challenging task since the indented volume must provide information of the bulk composite, i.e. contain enough reinforcement particles. The composites were fabricated by combining hot extrusion and compression moulding. Physico-chemical characterization by TGA and DSC indicates that Mg anticipates the thermal degradation of the polymers but does not compromise their stability during processing. Especial emphasis is devoted to determine the effect of strain rate and Mg content on mechanical behavior, thus important information about the visco-elastic behavior and time-dependent response of the composites is obtained. Relevant for the intended application is that Mg addition increases the elastic modulus and hardness of the polymeric matrices and induces a higher resistance to flow. The elastic modulus obtained by DSI experiments shows good agreement with that obtained by uniaxial compression tests. The results indicate that DSI experiments are a reliable method to calculate the modulus of polymeric composites reinforced with micro-particles. Taking into consideration the mechanical properties results, PLA/Mg composite could be used as substitute for biodegradable monolithic polymeric implants already in the market for orthopedics (freeform meshes, mini plates, screws, pins, …), craniomaxillofacial, or spine.

Local release from affinity-based polymers increases urethral concentration of the stem cell chemokine CCL7 in rats

The protein chemokine (C-C motif) ligand 7 (CCL7) is significantly over-expressed in urethral and vaginal tissues immediately following vaginal distention in a rat model of stress urinary incontinence. Further evidence, in this scenario and other clinical scenarios, indicates CCL7 stimulates stem cell homing for regenerative repair. This CCL7 gradient is likely absent or compromised in the natural repair process of women who continue to suffer from SUI into advanced age. We evaluated the feasibility of locally providing this missing CCL7 gradient by means of an affinity-based implantable polymer. To engineer these polymers we screened the affinity of different proteoglycans, to use them as CCL7-binding hosts. We found heparin to be the strongest binding host for CCL7 with a 0.323 nM dissociation constant. Our experimental approach indicates conjugation of heparin to a polymer backbone (using either bovine serum albumin or poly (ethylene glycol) as the base polymer) can be used as a delivery system capable of providing sustained concentrations of CCL7 in a therapeutically useful range up to a month in vitro. With this approach we are able to detect, after polymer implantation, significant increase in CCL7 in the urethral tissue directly surrounding the polymer implants with only trace amounts of human CCL7 present in the blood of the animals. Whole animal serial sectioning shows evidence of retention of locally injected human mesenchymal stem cells (hMSCs) only in animals with sustained CCL7 delivery, 2 weeks after affinity-polymers were implanted.