The development of microfabricated solenoids with magnetic cores for micromagnetic neural stimulation

Electrical stimulation via invasive microelectrodes is commonly used to treat a wide range of neurological and psychiatric conditions. Despite its remarkable success, the stimulation performance is not sustainable since the electrodes become encapsulated by gliosis due to foreign body reactions. Magnetic stimulation overcomes these limitations by eliminating the need for a metal-electrode contact. Here, we demonstrate a novel microfabricated solenoid inductor (80 µm × 40 µm) with a magnetic core that can activate neuronal tissue. The characterization and proof-of-concept of the device raise the possibility that micromagnetic stimulation solenoids that are small enough to be implanted within the brain may prove to be an effective alternative to existing electrode-based stimulation devices for chronic neural interfacing applications.

Reconstructing Nanohydroxyapatite Prosthesis Based on CT-Scanning Data and Its Application in Spinal Injury

This study investigated the nanohydroxyapatite (nHA) prosthesis application effect based on CT-scanning data in spinal injury. This study chose 26 spinal injury patients treated in our hospital from September 2017 to September 2018, who were randomly divided into two groups. nHA prosthesis based on CT-scanning data was implanted in the nHA group, whereas titanium mesh was implanted in the titanium mesh group. Consequently, osteoblasts were cultured to test the biological activity of nHA and titanium alloy. In cell tests, we found osteoblasts could better adhere to nHA, and proliferation and activity were higher when planted on nHA material. After surgical treatment, all patients’ spinal symptoms (VAS score, JOA score, and Cobb angle) had improved and did not cause obvious inflammatory foreign body reactions. During a two-year follow-up, the fusion time and support settlement in the nHA group was lower, and the vertebral fusion rate and ASIA score were higher than those in the titanium mesh group. Thus, CT-scanning data could further improve the vertebral fusion rate in the nHA group. Consequentially, nHA prosthesis based on CT-scanning data is a better choice for spinal injury therapy.

A Poly-Chitosan and Cis-Platinum Conjugated Composite Nanoparticle System for Liver Cancer Therapy

The aim of this study was to test an effective nano-pole capsule loaded cis-platinum (CP) transplantation device for liver cancer (LC) therapy. A novel nano-pole capsule was designed as a new vector for storing CP. HepG2 cells and a B6/J mouse model were used to test the efficiency of polyethyleneimine-cis-platinum (PEI-CP) and poly-chitosan-cis-platinum (PC-CP). Infiltration efficiency and transplantation efficiency tests were performed to study the performance of the delivery system, and fibroblast reactions and macrophage numbers were observed, to test for immune rejection and foreign body reactions. The apoptosis rate and tumor diameter of hepatocellular carcinoma cells were used to evaluate the effect of the tumor therapy. We also studied the functional mechanism of different CP delivery systems. The infiltration and transplantation efficiencies of PC-CP were higher than that of PEI-CP; Less foreign body reaction appeared in PC system, with less fibroblast reaction and lower macrophage reaction. The clinical efficacy of PC-CP in terms of tumor apoptosis and diameter reduction was superior to that of PEI-CP. We demonstrated that PC-CP had a more significant alteration effect on mTOR, P-Ak, LC3 and P53. The PC system can better deliver and release drugs than PEI-CP, and may be a better choice for LC therapy in the future.

Early Failure of a Polyvinyl Alcohol Hydrogel Implant With Osteolysis and Foreign Body Reactions in an Ovine Model of Cartilage Repair

Background: Hemiarthroplasty using a polyvinyl alcohol (PVA) hydrogel synthetic implant has been suggested as a good alternative to arthrodesis for the treatment of hallux rigidus. However, failure rates as high as 20% have been recorded. Purpose: To characterize the pathological processes in bone, cartilage, and the synovial membrane after PVA hemiarthroplasty in an ovine model with 6 months of follow-up. Study Design: Controlled laboratory study. Methods: A unilateral osteochondral defect (8-mm diameter × 10-mm depth) was made in the medial femoral condyle in 6 sheep. Animals were randomized to receive a PVA implant (n = 4) or to have an empty defect (n = 2) and were monitored for 6 months. Patellofemoral radiographs were obtained at monthly intervals, and quantitative computed tomography was performed at the end of the study. After death, the joints were macroscopically evaluated and scored. Osteochondral and synovial membrane histological findings were assessed using modified Osteoarthritis Research Society International (OARSI) and aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) scoring systems. Immunohistochemistry using Iba1 was performed to evaluate activated macrophage infiltration. Results: Overall, 2 sheep with PVA implants were euthanized at 1 and 5 months because of uncontrollable pain and lameness (failed implants). Quantitative computed tomography showed that sheep with failed implants had 2.1-fold more osteolysis than those with successful implants. The sheep with failed implants had osteoarthritis with extensive glycosaminoglycan loss and cartilage fibrillation of the condyle and opposing tibial surface on histological examination. A foreign body reaction with severe chronic lymphoplasmacytic and granulomatous inflammation with giant cells was detected surrounding the implant. The synovial membrane ALVAL score was 9 of 19 and 14 of 19 in failed implants with synovial hyperplasia and lymphoplasmacytic and macrophage infiltration. In contrast, the synovial membrane in successful implants and empty defects was normal (ALVAL score = 0/19). Immunolabeling for Iba1 in failed implants confirmed extensive and dense macrophage infiltration within the condyle and synovial membrane, with the highest immunoreactive score (9/9). Conclusion: PVA hydrogel implants had a 50% failure rate with uncontrollable pain, severe osteolysis, inflammation, and foreign body reactions. Clinical Relevance: The failure rate and pathological characteristics of the PVA implants suggest that their use should not be continued in human patients without further in vivo safety studies.

Functionalization of Silicone Surface with Drugs and Polymers for Regulation of Capsular Contracture

Breast reconstruction is achieved using silicone implants, which are currently associated with major complications. Several strategies have been considered to overcome the existing limitations as well as to improve their performance. Recently, surface modification has proved to be an effective clinical approach to prevent bacterial adhesion, reduce capsular thickness, prevent foreign body reactions, and reduce other implant-associated problems. This review article summarizes the ongoing strategies for the surface modification of silicone implants in breast reconstruction applications. The article mostly discusses two broad categories of surface modification: drug-mediated and polymer-based. Different kinds of drugs have been applied with silicone that are associated with breast reconstruction. Initially, this article discusses studies related to drugs immobilized on silicone implants, focusing on drug-loading methods and their effects on capsule contracture. Moreover, the pharmacological action of drugs on fibroblast cells is considered in this section. Next, the polymeric modification of the silicone surface is introduced, and we discuss its role in reducing capsule thickness at the cellular and biological levels. The polymeric modification techniques, their chemistry, and their physical properties are described in detail. Notably, polymer activities on macrophages and inflammation are also briefly discussed. Each of the reviewed articles is summarized, highlighting their discussion of capsular thickness, foreign body reactions, and bacterial attachment. The aim of this review is to provide the main points of some research articles regarding the surface modification of silicon, which can lead to a decrease in capsular thickness and provides better patient compliance.

Ahmed implant coated with poly(2-methacryloyloxyethyl phosphorylcholine) inhibits foreign body reactions in rabbit eyes

Purpose Wound healing after Ahmed glaucoma valve (AGV) implantation often entails fibrosis as a foreign body reaction to the silicone plate. Poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) forms an antifouling surface that inhibits fibrosis during wound healing. In this study, we aimed to compare the effects of the implantation of AGV coated with PMPC (wPMPC) versus AGV without PMPC (woPMPC) in rabbits. Methods Six New Zealand White rabbit does underwent AGV implantation in both eyes. For each rabbit, one eye was randomly selected for implantation of AGV wPMPC and a conventional AGV (woPMPC) was implanted in the contralateral eye. Gross conjunctival vascularity was compared between the two groups at the first, second, and fourth weeks after surgery. The eyes were enucleated in four weeks and subjected to staining with hematoxylin and eosin and Masson’s trichrome stain. The fibrosis and inflammation status among the eye samples were compared by measuring the thickness of the fibrotic walls and counting the number of chronic inflammatory cells around the AGV. Counting of inflammatory cells and measuring fibrotic wall thickness were done in a blinded method to eliminate observer bias. Statistical analysis was performed using the Mann-Whitney U test. Results Gross and histological examinations revealed no toxic effects of PMPC. There were no apparent differences in overall conjunctival vascularity between the two groups at weeks 1, 2, and 4 after surgery. The average inflammatory cell counts were 14.3 ± 5.8 per slide and 27.3 ± 8.6 per slide in the wPMPC and woPMPC groups, respectively (p = 0.037). The average thicknesses of the fibrotic wall were 57.9 ± 11.3 μm and 81.5 ± 21.3 μm in the wPMPC and woPMPC groups, respectively (p = 0.025). Conclusion Compared to the woPMPC group, the number of inflammatory cells and fibrosis were significantly decreased in the wPMPC group.

Alveogyl: Foreign Body Reaction

Alveolar osteitis (AO) is a painful complication experienced by approximately 3–4% of patients who have undergone a dental extraction. A frequently used intra-alveolar dressing material, such as Alveogyl is commonly used to treat sockets where a diagnosis of AO is made. However, unexpected problems may be encountered by the dentist when using such materials and this article explores a case where a diagnosis of a foreign body reaction to Alveogyl was identified in a symptomatic patient with no overt clinical or radiographical signs. CPD/Clinical Relevance: Dental professionals should be aware of the possible complications with the use of Alveogyl in the treatment of alveolar osteitis, in particular foreign body reactions.

Bone Coverage around Hydroxyapatite/Poly(L-Lactide) Composite Is Determined According to Depth from Cortical Bone Surface in Rabbits

Composites of unsintered hydroxyapatite (HA) and poly(L-lactide) (PLLA) reinforced by compression forging are biodegradable, bioactive, and have ultrahigh strength. However, foreign body reactions to PLLA and physical irritation can occur when not covered by bone. We aimed to confirm the relationships between the depth of the implanted HA-PLLA threaded pins and the new bone formation. We inserted HA-PLLA composite threaded pins (diameter: 2.0 or 4.5 mm) into the femoral and tibial bones of 32 mature male Japanese white rabbits (weight 3.0–3.5 kg) with the pin head 1 or 0 mm below or protruding 1 or 2 mm above surrounding cortical bone. Eight euthanized rabbits were radiologically and histologically assessed at various intervals after implantation. Bone bridging was complete over pins of both diameters at ~12 weeks, when inserted 1 mm below the surface, but the coverage of the pins inserted at 0 mm varied. Bone was not formed when the pins protruded >1 mm from the bone surface. No inflammation developed around the pins by 25 weeks. However, foreign body reactions might develop if composites are fixed above the bone surface, and intraosseous fixation would be desirable using double-threaded screws or a countersink to avoid screw head protrusion.

Prosthetic Meshes for Hernia Repair: State of Art, Classification, Antimicrobial Approaches, and Fabrication Methods

Worldwide, hernia repair represents one of the most frequent surgical procedures encompassing a global market valued at several billion dollars. This type of surgery usually requires the implantation of a mesh that needs the appropriate chemical, physical and biological properties for the type of repair. This review thus presents a description of the types of hernias, current hernia repair methods, and the state of the art of prosthetic meshes for hernia repair providing the most important meshes used in clinical practice by surgeons working in this area classified according to their biological or chemical nature, morphology and whether bioabsorbable or not. We emphasise the importance of surgical site infection in herniatology, how to deal with this microbial problem, and we go further into the future research lines on the production of advanced antimicrobial meshes to improve hernia repair and prevent microbial infections, including multidrug-resistant strains. A great deal of progress has been made in this biomedical field in the last decade. However, we are still far from an ideal antimicrobial mesh that can also provide excellent integration to the abdominal wall, mechanical performance, low visceral adhesion and minimal inflammatory or foreign body reactions, among many other problems.

Novel Graphene Electrode for Retinal Implants: An in vivo Biocompatibility Study

Evaluating biocompatibility is a core essential step to introducing a new material as a candidate for brain-machine interfaces. Foreign body reactions often result in glial scars that can impede the performance of the interface. Having a high conductivity and large electrochemical window, graphene is a candidate material for electrical stimulation with retinal prosthesis. In this study, non-functional devices consisting of chemical vapor deposition (CVD) graphene embedded onto polyimide/SU-8 substrates were fabricated for a biocompatibility study. The devices were implanted beneath the retina of blind P23H rats. Implants were monitored by optical coherence tomography (OCT) and eye fundus which indicated a high stability in vivo up to 3 months before histology studies were done. Microglial reconstruction through confocal imaging illustrates that the presence of graphene on polyimide reduced the number of microglial cells in the retina compared to polyimide alone, thereby indicating a high biocompatibility. This study highlights an interesting approach to assess material biocompatibility in a tissue model of central nervous system, the retina, which is easily accessed optically and surgically.