Medical applications of biopolyesters polyhydroxyalkanoates

Microbial polyhydroxyalkanoates(PHAs) are a family of biopolyesters produced by many wild type and engineered bacteria.PHAs have diverse structures accompanied by flexible thermal and mechanical properties.Combined with their in vitro biodegradation,cell and tissue compatibility,PHAs have been studied for medical applications,especially medical implants applications,including heart valve tissue engineering,vascular tissue engineering,bone tissue engineering,cartilage tissue engineering,nerve conduit tissue engineering as well as esophagus tissue engineering.Most studies have been conducted in the authors’ lab in the past 20+ years.Recently,mechanism on PHA promoted tissue regeneration was revealed to relate to cell responses to PHA biodegradation products and cell-material interactions mediated by microRNA.Very importantly,PHA implants were found not to cause carcinogenesis during long-term implantation.Thus,PHAs should have a bright future in biomedical areas.     

Advances in the ultrastructural study of the implant-bone interface by backscattered electron imaging

The biocompatibility of titanium implants in bone depends on the response shown by cells in contact with the implant surface. Several developments have been targeted at achieving successful implant treatment. The aim of this study was to develop a novel preparation procedure to evaluate the bone cell response produced at the bone–implant interface using the technique scanning electron microscopy with backscattered electron imaging (SEM-BSE). Dental prostheses with an SLA-modified or TOP-modified surface were implanted in a toothless part of the mandibula in female pigs. The animals were sacrificed 12 weeks after surgery, at which time block specimens containing the implants were obtained. These specimens were then processed for SEM-BSE by optimizing a protocol involving chemical fixation and heavy metal staining. In addition, element distribution maps for the implant–bone tissue interface were obtained using a microanalytical system based on energy-dispersive X-ray spectrometry (EDS). This novel visualisation approach enabled a comprehensive study of the extracellular matrix and cell components of the host tissues neoformed around the implant. SEM-BSE images also provided ultrastructural details of the bone cells. This technique appears to be an effective and very promising tool for detailed studies on the implant–bone tissue interface and the host response to the bone incorporation process.     

Effect of strontium substitution on the composition and microstructure of sol–gel derived calcium phosphates

Sr-doped calcium phosphates have been prepared by sol–gel chemistry. All samples exhibit two phases: hydroxyapatite (HAp) and tricalcium phosphate (β-TCP). With respect to undoped sample, the Sr-doped samples exhibit higher proportion of β-TCP phase but the quantity appears to be quite independent of the doping level. To explain the mismatch with the nominal stoichiometry, the presence of amorphous CaO and SrO compounds have been postulated and their proportions evaluated. The insertion of Sr²⁺ ions in the two crystalline phases HAp and β-TCP is almost total for low doping levels but quite incomplete for the highest doping level. The majority of the inserted Sr²⁺ ions are in the β-TCP phase. Considering the acknowledged beneficial effect of Sr²⁺ on the bone regeneration process, the effective partial substitution of Sr in biphasic calcium phosphate makes these materials very interesting for clinical applications. The Sr-substituted HAp and β-TCP cell parameters agree fairly well with the Vegard’s law and Sr²⁺ ions substitute preferentially for Ca²⁺ in the Ca2 site for hydroxyapatite and in the Ca4 site for β-TCP. The microstructural parameters confirm the previous observation and give a new evidence of clear stabilizing effect of Sr²⁺ ions towards the β-TCP structure.     

Surface free energy effect on bacterial retention

Bacterial infection is one of the most frequent and severe complications in the long-term effectiveness of medical implants and devices, greatly increasing treatment cost and inconvenience to the patient. Surface physical and chemical properties are known to influence the extent and form of bacterial infection, although the exact correlation with specific properties is difficult due to the complexity of the system. One approach in the attempt to reduce the bacterial colonisation is to modify the surface energy and chemistry, so as to influence the interactions between the surface and the bacteria that come into contact with it. Five types of coatings were investigated in this study, together with silicone, and polished and non-polished stainless steel 316L. Surfaces were tested for retention of Pseudomonas aeruginosa AK1 after 1 h. A good correlation (>90%) was found between P. aeruginosa AK1 retention and total surface free energy, as well as its polar and dispersive components. The minimum level of P. aeruginosa AK1 retention was found for a range of total surface free energy in the range 20–27 mN/m.     

Septal repair implants: evaluation of magnetic resonance imaging safety at 3 T

Specialized implants are used for transcatheter closure of septal defects, including atrial and ventricular septal defects, and patent foramen ovale. These metallic devices may pose a risk to patients undergoing magnetic resonance imaging (MRI) procedures especially if performed at 3 T. Therefore, this investigation evaluated MRI safety at 3 T for septal repair implants (CardioSEAL Septal Repair Implant and STARFlex Septal Repair Implant, NMT Medical, Boston, MA, USA) by characterizing magnetic field interactions, heating and artifacts. These implants exhibited minor magnetic field interactions; heating was not excessive (+0.5°C); and artifacts will only create a problem if the area of interest is in the same area as or near these devices. Thus, the findings indicated that it would be safe for a patient with these implants to undergo MRI at 3 T or lower. Importantly, because of the minor magnetic field interactions, MRI may be performed immediately after implantation.     

Experimental Methods in Testing of Tissues and Implants*

Three experimental tasks are of primary interest in biomechanics: determination of the mechanical properties of biomaterials, including tissues and artificial materials; validation of the mechanical reliability of implantable devices; assessment of the compatibility of the mechanical properties of such devices with the surrounding biological environment. Due to the complexity of the in vivo conditions, most of these studies are performed on in vitro models. This contribution presents a review of some methods that are currently utilised at the Laboratory of Biological Structure Mechanics at the Politecnico of Milan.     

A new vascular coupling device: Assessment of MRI issues at 3-tesla

Objective

Vascular grafting frequently involves a time-consuming operation. A new vascular coupling device (VCD) made from metallic material was recently developed that may be advantageous because of the reduced operative time and decreased patient risks. Because of the metal, there are safety concerns related to MRI. Therefore, the purpose of this investigation was to use standardized testing techniques to evaluate MRI issues for this VCD in association with a 3-Tesla MR system.

Methods

The VCD (corlife oHG, Hannover, Germany) was evaluated for magnetic field interactions (translational attraction and torque), MRI-related heating, and artifacts at 3-Tesla. MRI-related heating was assessed with the VCD in a gelled-saline-filled phantom with MRI performed at a whole body averaged SAR of 2.9-W/kg for 15-min. Artifacts were assessed using T1-weighted, spin echo, and gradient echo pulse sequences.

Results

The VCD exhibited minor magnetic field interactions and minimal heating (maximum temperature elevation, 1.8 °C). Artifacts were relatively small in relation to the size and shape of this implant. The lumen of the VCD could not be visualized using the gradient echo pulse sequence.

Conclusions

The metallic VCD that underwent evaluation is MR conditional for a patient undergoing an MRI procedure at 3-Tesla or less.     

RF-related heating assessment of extracranial neurosurgical implants at 7 T

Purpose

The purpose was to evaluate radiofrequency (RF)-related heating of commonly used extracranial neurosurgical implants in 7-T magnetic resonance imaging (MRI).

Materials and methods

Experiments were performed using a 7-T MR system equipped with a transmit/receive RF head coil. Four commonly used titanium neurosurgical implants were studied using a test procedure adapted from the American Society for Testing and Materials Standard F2182-11a. Implants (n = 4) were tested with an MRI turbo spin echo pulse sequence designed to achieve maximum RF exposure [specific absorption rate (SAR) level = 9.9 W/kg], which was further validated by performing calorimetry. Maximum temperature increases near each implant's surface were measured using fiberoptic temperature probes in a gelled-saline-filled phantom that mimicked the conductive properties of soft tissue. Measurement results were compared to literature data for patient safety.

Results

The highest achievable phantom averaged SAR was determined by calorimetry to be 2.0 ± 0.1 W/kg due to the highly conservative SAR estimation model used by this 7-T MR system. The maximum temperature increase at this SAR level was below 1.0 °C for all extracranial neurosurgical implants that underwent testing.

Conclusion

The findings indicated that RF-related heating under the conditions used in this investigation is not a significant safety concern for patients with the particular extracranial neurosurgical implants evaluated in this study.     

Theoretical evaluation of peripheral nerve stimulation during MRI with an implanted spinal fusion stimulator

This study examines the requirements for nerve excitation near a spinal fusion implant during magnetic resonance imaging. The implant is the Spinal Fusion SpF^® device manufactured by Electro Biology Inc. The electric field induced within the biological medium was calculated using a three-dimensional finite difference model (described in a separate paper by Beuchler et al. from the University of Utah). Magnetic thresholds were obtained for excitation of myelinated nerve fibers that are near the implant. Minimum (rheobase) thresholds were determined for long duration dB/dt pulses, as well as strength-duration time constants (from which thresholds at other durations could be determined) for various geometries between the implant and a myelinated nerve fiber. The lowest thresholds occur when a large (20-μm diameter) fiber is situated near the bare tip of a wire from the implant, and a long duration (2 ms) stimulus is provided for which dB/dt is constant and monophasic. Magnetic thresholds for shorter durations of dB/dt are higher in accordance with a strength-duration law. In a magnetic field having a time derivative of 10 T/s that is uniform over the torso, nerve excitation is possible under worst-case conditions only for nerve fibers that are within 0.14 mm of the bare wire tip of the implant. With 20 T/s, excitation is possible only within 1 mm of the wire tip.     

A novel graded bioactive high adhesion implant coating

One method to increase the clinical success rate of metal implants is to increase their bone bonding properties, i.e. to develop a bone bioactive surface leading to reduced risks of interfacial problems. Much research has been devoted to modifying the surface of metals to make them become bioactive. Many of the proposed methods include depositing a coating on the implant. However, there is a risk of coating failure due to low substrate adhesion. This paper describes a method to obtain bioactivity combined with a high coating adhesion via a gradient structure of the coating. Gradient coatings were deposited on Ti (grade 5) using reactive magnetron sputtering with increasing oxygen content. To increase the grain size in the coating, all coatings were post annealed at 385 °C. The obtained coating exhibited a gradual transition over 70 nm from crystalline titanium oxide (anatase) at the surface to metallic Ti in the substrate, as shown using cross-section transmission electron microscopy and X-ray photoelectron spectroscopy depth profiling. Using scratch testing, it could be shown that the adhesion to the substrate was well above 1 GPa. The bioactivity of the coating was verified in vitro by the spontaneous formation of hydroxylapatite upon storage in phosphate buffer solution at 37 °C for one week.The described process can be applied to implants irrespective of bulk metal in the base and should introduce the possibility to create safer permanent implants like reconstructive devices, dental, or spinal implants.