Implants In Non-human Primates Research Articles

3D printed guide tube system for acute Neuropixels probe recordings in non-human primates

Objective. Neuropixels (NP) probes are a significant advance in electrophysiological recording technology that enable monitoring of hundreds of neurons in the brain simultaneously at different depths. Application of this technology has been predominately in rodents, however widespread use in non-human primates (NHPs) such as rhesus macaques has been limited. In this study we sought to overcome two overarching challenges that impede acute NP implantation in NHPs: (1) traditional microdrive systems that mount to cephalic chambers are commonly used to access cortical areas for microelectrode recordings but are not designed to accommodate NP probes, and (2) NHPs have thick dura mater and tissue growth within the cephalic chambers which poses a challenge for insertion of the extremely fragile NP probe. Approach. In this study we present a novel NP guide tube system that can be adapted to commercial microdrive systems and demonstrate an implant method using the NP guide tube system. This system was developed using a combination of CAD design, 3D printing, and small part machining. Software programs, 3D Slicer and SolidWorks were used to target cortical areas, approximate recording depths and locations, and for in-silico implant testing. Main results. We performed in vivo testing to validate our methodology, successfully implanting, explanting, and reimplanting NP probes. We collected stable neurophysiological recordings in the premotor cortex of a rhesus macaque at rest and during performance of a reaching task. Significance. In this study we demonstrate a robust Neuropixels implant system that allows multiple penetrations with the same NP probe and share design files that will facilitate the adoption of this powerful recording technology for NHP studies.

Cervical subtotal discectomy prosthesis validated in non-human primate model: A novel artificial cervical disc replacement concept?

Objective: To evaluate the biological function of cervical subtotal discectomy prosthesis (CSDP) implantation in a non-human primate model. Methods: A CSDP was tested for cytocompatibility and osseointegration capacity before implantation in non-human primates. Subsequently, the CSDP was improved based on three-dimensional CT measurements of the non-human primate cervical spine. Eight cynomolgus monkeys were selected for removal of the intervertebral disc and lower endplate of the C5/6 segment to complete the model construction for CSDP implantation. In 18-month follow-up, physiological indices, radiology, and kinematics were assessed to estimate the biological function of the CSDP in non-human primates, including biosafety, osseointegration, and biomechanics. Results: Co-cultured with the CSDP constituent titanium alloy (Ti6Al4V-AO), the mouse embryo osteoblast precursor cell MC3T3-E1 obtained extended adhesion, remarkable viability status, and cell proliferation. After implantation in the mouse femur for 28 days, the surface of Ti6Al4V-AO was covered by a large amount of new cancellous bone, which formed further connections with the femur cortical bone, and no toxicity was detected by blood physiology indices or histopathology. After completing implantation in primate models, no infection or osteolysis was observed, nor was any subsidence or displacement of the CSDP observed in CT scans in the 18-month follow-up. In particular, the interior of the cervical vertebra fixation structure was gradually filled with new trabecular bone, and the CSDP had achieved fixation and bony fusion in the vertebral body at 1 year post-operation. Meanwhile, no signs of inflammation, spinal cord compression, adjacent segment degeneration, or force line changes were observed in subsequent MRI observations. Moreover, there were no pathological changes of the joint trajectory, joint motion range, stride length, or the stance phase ratio revealed in the kinematics analysis at 3, 6, 12, or 18 months after CSDP implantation. Conclusion: We successfully designed a new cervical subtotal discectomy prosthesis and constructed an excellent non-human primate implantation model for the evaluation of subtotal disc replacement arthroplasty. Furthermore, we demonstrated that CSDP had outstanding safety, osseointegration capacity, and biomechanical stability in a non-human primate model, which might be a new choice in the treatment of cervical disc diseases and potentially change future outcomes of degenerative cervical diseases.

Local FK506 implants in non-human primates to prevent early acute rejection in vascularized composite allografts.

BackgroundPrevious vascularized composite allograft (VCA) studies from our laboratory have shown that topical FK506 delivery in non-human primates (NHPs) was limited by inadequate dermal penetration and rejection persisted. Herein, we report the first utilization of FK506 via subcutaneously implanted discs to mitigate VCA rejection in NHPs.MethodsFull major histocompatibility complex (MHC)-mismatched NHP pairs underwent partial-face VCA and FK506 disc implantation along the suture line. All allotransplants were maintained post-operatively for two months on the FK506 discs, methylprednisolone, mycophenolate mofetil, and supplemented with intramuscular FK506 if necessary. Group 1 (n=4) was used for optimization of the implant, while Group 2 (n=3) underwent delayed bone marrow transplantation (DBMT) after two months. VCA skin biopsies and peripheral blood samples were obtained for serial assessment of rejection and mixed chimerism by histopathology and flow cytometry respectively.ResultsIn Group 1, two technical failures occurred. Of the remaining two NHPs, one developed supratherapeutic levels of FK506 (50–120 ng/mL) and had to be euthanized on postoperative day (POD) 12. Reformulation of the implant resulted in stable FK506 levels (20–30 ng/mL) up to POD12 when further intramuscular (IM) FK506 injections were necessitated. In Group 2, two NHPs survived to undergo conditioning and one successfully developed chimerism at 2–3 weeks post-DBMT (96–97% granulocytes and 7–11% lymphocytes of recipient-origin). However, all three NHPs had to be terminated from study at POD64, 77 and 86 due to underlying post-transplant lymphoproliferative disorder. All VCAs remained rejection-free up to study endpoint otherwise.ConclusionsThis study shows preliminary results of local FK506 implants in potentially mitigating VCA acute rejection for tolerance protocols based on mixed chimerism approach.

The Accuracy and Feasibility of Robotic Assisted Lead Implantation in Nonhuman Primates

Deep brain stimulation (DBS) and stereo-electroencephalography (SEEG) electrode implantation are the most important and frequent manipulations in nonhuman primates (NHP) neuromodulation research. However, traditional methods tend to be arduous and inaccurate. Twelve adult male rhesus monkeys were selected for the study, with six subthalamic nucleus (STN) DBS, six anterior nucleus of the thalamus (ANT) DBS and six hippocampus-SEEG (Hippo-SEEG) electrodes implantation. Mean Euclidean errors of entrance and the target were calculated by postoperative image fusion, and the correlation between entrance and target error, as well as the differences among the various manipulations, were analyzed. The accuracy of target was further confirmed by gross anatomy examination. Moreover, the time consumption was recorded. The mean (±SD) Euclidean errors of the target point and entry point of the three manipulations were STN-DBS: 1.05 ± 0.54 mm and 0.52 ± 0.17 mm; ANT-DBS: 1.12 ± 0.74 mm and 0.58 ± 0.24 mm; and Hippo-SEEG: 2.68 ± 1.03 mm and 1.47 ± 0.63 mm. Significant differences were observed in both target and entry point errors between the DBS and Hippo-SEEG groups, with superior accuracy in the DBS group. The entrance errors had a significantly positive correlation with the target errors in the STN-DBS and Hippo-SEEG groups. Moreover, the time consumption in robotic surgery was much shorter than that in the traditional method, without any severe complications. The application of robot-assisted lead implantation in NHP neuromodulation research is feasible, accurate, safe, and efficient, and can prospectively be beneficial to neurological studies.

Improved methods for MRI-compatible implants in nonhuman primates

BackgroundNeuroscientists commonly use permanently implanted headposts to stabilize the head of nonhuman primates (NHPs) during electrophysiology and functional magnetic resonance imaging (fMRI). Here, we present improved methodology for MRI-compatible implants without the use of acrylic for head stabilization in NHPs. New methodMRI is used to obtain a 3D-reconstruction of NHP skulls, which are used to create customized implants by modeling intersections with the bone. Implants are manufactured from PEEK using computer numerical control machining and coated with hydroxyapatite to promote osseointegration. Surgically, implants are attached to the skull with ceramic screws, while the skin flap is pulled over the implant and closed subcutaneously. ResultsQuality of blood oxygen level dependent (BOLD) fMRI signal is improved in animals implanted with our method as compared to traditional acrylic implants. Additionally, implants are well-integrated with the skull, remain robust for more than a year and without granulation tissue around the skin margin. Comparison with existing method(s)Previous improvements on NHP implants (Chen et al., 2017; McAndrew et al., 2012; Mulliken et al., 2015; Overton et al., 2017) lacked fMRI-compatibility, as they relied on titanium headposts and/or titanium screws. Thus, most fMRI studies in NHPs today still rely on the use of acrylic-based headposts for stabilization and the use of contrast-enhanced agents to improve MRI signal. ConclusionsOur method preserves fMRI-compatibility and results in measurable improvement in BOLD signal without the use of contrast-enhanced agents. Furthermore, the long-term stability of our implants contributes positively to the wellbeing of NHPs in neuroscience research.

Improved methods for acrylic-free implants in nonhuman primates for neuroscience research.

Traditionally, head fixation devices and recording cylinders have been implanted in nonhuman primates (NHP) using dental acrylic despite several shortcomings associated with acrylic. The use of more biocompatible materials such as titanium and PEEK is becoming more prevalent in NHP research. We describe a cost-effective set of procedures that maximizes the integration of headposts and recording cylinders with the animal's tissues while reducing surgery time. Nine rhesus monkeys were implanted with titanium headposts, and one of these was also implanted with a recording chamber. In each case, a three-dimensional printed replica of the skull was created based on computerized tomography scans. The titanium feet of the headposts were shaped, and the skull thickness was measured preoperatively, reducing surgery time by up to 70%. The recording cylinder was manufactured to conform tightly to the skull, which was fastened to the skull with four screws and remained watertight for 8.5 mo. We quantified the amount of regression of the skin edge at the headpost. We found a large degree of variability in the timing and extent of skin regression that could not be explained by any single recorded factor. However, there was not a single case of bone exposure; although skin retracted from the titanium, skin also remained adhered to the skull adjacent to those regions. The headposts remained fully functional and free of complications for the experimental life of each animal, several of which are still participating in experiments more than 4 yr after implant.NEW & NOTEWORTHY Cranial implants are often necessary for performing neurophysiology research with nonhuman primates. We present methods for using three-dimensional printed monkey skulls to form and fabricate acrylic-free implants preoperatively to decrease surgery times and the risk of complications and increase the functional life of the implant. We focused on reducing costs, creating a feasible timeline, and ensuring compatibility with existing laboratory systems. We discuss the importance of using more biocompatible materials and enhancing osseointegration.

Improved stereotactic procedure enhances the accuracy of deep brain stimulation electrode implantation in non-human primates

Purpose: Non-human primate models of deep brain stimulation (DBS) play an increasingly important role in the exploration of DBS mechanisms. The establishment and recognized usefulness of such models depend on the precise positioning of the stimulating targets and electrode implants. The optimal method of targeting remains controversial. Materials and methods: This paper described an improved stereotactic procedure that uses a self-developed adaptor to improve accuracy. This involved: (1) connecting clinical stereotactic devices with the skull of primates using a self-developed adaptor; (2) pre-operation targeting via magnetic resonance imaging (MRI); (3) target re-checking by microelectrode recording (MER); (4) DBS electrode implantation; (5) post-operative MRI verification of electrode placement and (6) positioning confirmation by DBS programming. Results: Use of the adaptor enabled clinical stereotactic surgery, pre-operative MRI targeting, microelectrode mapping and post-operative verification in primate DBS operations. Discrepancies between achieved and predetermined electrode position were around 0.6 mm. DBS programming improved the motor function of the hemiparkinsonism animals and decreased the numbers of rotation induced by apomorphine, indicating the precise positioning of the stimulating target and successful implanting of electrode using this method. Conclusions: An improved stereotactic procedure was performed during a non-human primate DBS operation using a self-developed adaptor. The accuracy of DBS electrode implantation in non-human primates was improved with this method.

Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration

Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix), and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the rational design of extracellular matrix products and bioscaffolds of tissue engineering.

Corrigendum

Clinical Oral Implants ResearchVolume 20, Issue 11 p. 1299-1299 Free Access Corrigendum This article corrects the following: Long-term effects of magnetron-sputtered calcium phosphate coating on osseointegration of dental implants in non-human primates Fügl Alexander, Ulm Christian, Tangl Stefan, Vasak Christoph, Gruber Reinhard, Watzek Georg, Volume 20Issue 2Clinical Oral Implants Research pages: 183-188 First Published online: January 21, 2009 First published: 11 October 2009 https://doi.org/10.1111/j.1600-0501.2009.01851.xAboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat In Fügl et al. (2009), the authors' names were listed as below on page 183: Fügl Alexander Ulm Christian Tangl Stefan Vasak Christoph Gruber Reinhard Watzek Georg The order of the authors' family and given names is incorrect and should have been: Alexander Fügl Christian Ulm Stefan Tangl Christoph Vasak Reinhard Gruber Georg Watzek Reference Fügl, A., Ulm, C., Tangl, S., Vasak, C., Gruber, R. & Watzek, G. (2009) Long-term effects of magnetron-sputtered calcium phosphate coating on osseointegration of dental implants in non-human primates. Clinical Oral Implants Research 20: 183– 188. doi: DOI: 10.1111/j.1600-0501.2008.01635.x. Volume20, Issue11November 2009Pages 1299-1299 ReferencesRelatedInformation

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Effects of Cochlear Nuclei Electrical Stimulation with Surface Brain Stem Implants in Nonhuman Primates

We undertook morphological evaluation of the cochlear nucleus complex (CNC) after implantation of a surface auditory brain stem implant (ABI). We used 14 nonhuman primates (Macaca fascicularis). They underwent translabyrinthine bilateral auditory deafferentation and simultaneous unilateral implantation of an ABI. In 6 cases the ABI was not activated, whereas it was activated in 8 cases. The ABI array consisted of 3 platinum disc electrodes mounted on a silicone pad with the back side covered with polyethylene terephthalate mesh, connected via a cable to an external stimulator in animals undergoing electrical stimulations. All animals tolerated the procedures well. In both groups of animals, neuropathologic lesions or changes attributed to surgical trauma were found. The biotolerance of neural tissue to the materials used was adequate. The stimulation times ranged from 0 to 732 hours. Neuropathologic examination and stereological assessment revealed that the animals showed no signs of significant neural damage after CNC chronic stimulation if this took place within the safety limits. Time of stimulation did not seem to play a significant role in changes. Besides surgical trauma, the most important factors responsible for CNC changes are the electrical stimulation parameters.

Bone Response to New Modified Titanium Surface Implants in Nonhuman Primates (Papio ursinus) and Humans: Histological Evaluation

The aim of this study is a comparative histological and histomorphometrical evaluation of the effect on early bone formation of 2 different implant surfaces: a machined and a new acid-etched implant surface (Leader, Milano, Italy). Ten screw-type microimplants were placed in 5 patients. Each patient received 2 microimplants (2 mm in diameter and 5 mm in length): 1 with a machined surface (control) and 1 with an acid-etched surface (test). The microimplants were retrieved after 60 days of healing with a 4-mm trephine bur and processed for histology. Moreover, 24 regular size implants--12 with a machined surface (control) and 12 with an acid-etched surface (test)--were placed in 2 adult nonhuman primates 3 months after the extraction of premolars and molars. Each animal received 3 machined implants (control) in the right hemimandible and 3 acid-etched implants (test) in the left hemimandible. The same animals received 3 control implants and 3 test implants in the rectus abdominis muscle. After 1 month, the implants were retrieved from the mandible and the rectus abdominis muscle and processed for histology. Histomorphometric evaluation demonstrated a higher bone-to-implant contact in the test implants compared with the controls in both primates (25.55% vs 15.8%) and humans (62% vs 45%). Moreover, in nonhuman primates after 1 month of healing, it was possible to observe a poor osseointegration in the control specimens, while newly formed bone in direct contact with test implants was evident. The rectus abdominis muscle specimens showed that the acid-etched surfaces can stimulate the formation and attachment of new connective and vascular tissues more than machined surfaces can. Implant surface geometry can speed up bone formation by the development of a special microenvironment that promotes angiogenesis. Long-term studies are needed to further test this new acid-etched implant surface.

Clinical and Histological Evaluation of Immediate-Loaded Posterior Implants in Nonhuman Primates

To evaluate a square-thread design implant and compare the bone-implant contact percentage between immediate-loaded and nonloaded implants (controls) in nonhuman primates. Five nonhuman primates each received 3 implants, with a total of 5 control implants and 10 immediate-loaded implants in posterior regions of the mouth. Ninety days after surgery (and function was appropriate), block sections of the implants were removed and sectioned in 200-mum thick pieces. The block sections were stained with modified Masson for evaluation of the bone-implant contact percentage. One of the immediate-loaded implants failed. The bone-implant contact percentage of control implants ranged from 50.34% to 64.13% and averaged 56.3%. The bone-implant contact percentage of immediate-loaded implants ranged from 43.23% to 75.72%, with an average of 62.4%. Two implants had lower bone-implant contact percentage than the others, and when these are not included in the evaluation, the bone-implant contact percentage average increased to 67.6%. Immediate-loaded implants in the nonhuman primates often have a higher bone-implant contact percentage at 90 days than unloaded implants. The bone remodeling is different for loaded implant-bone interfaces than for unloaded conditions. However, 1 immediate-loaded implant failed, and 2 implants had lower bone-implant contact percentage than controls. Therefore, although there are benefits of immediate loading, there appear to also be some risks.

Establishment of the need for oestrogen during implantation in non-human primates

Deprivation of oestrogen during post-ovulatory mated cycles in proven fertile female bonnet monkeys by tamoxifen, aromatase inhibitor or oestrogen antiserum resulted in inhibition of pregnancy establishment in all three groups of animals. However, more than 85% of the animals became pregnant within three exposures to proven fertile males in the control group. These results suggest the requirement for oestrogen in pregnancy establishment in primates. Based on this conclusion, it is suggested that use of a suitable and potent anti-oestrogenic compound can be exploited as an alternative approach to contraception.

Long-term gliosis around chronically implanted platinum electrodes in the Rhesus macaque motor cortex

Chronically implanted microelectrodes have been an important tool used by neuroscientists for many years and are critical for the development of neural prostheses designed to restore function after traumatic central nervous system (CNS) injury. It is well established that a variety of mammals, including non-human primates (NHP), tolerate noble metal electrodes in the cortex for extended periods of time, but little is known about the long-term effects of electrode implantation at the cellular level. While data from rodents have clearly shown gliosis around such implants, there have been difficulties in demonstrating these reactions in NHP. Glial reactions are to be expected in NHP, since any trauma to the mammalian CNS is believed to result in the formation of a glial scar consisting of reactive astrocytes and microglia around the injury site. Because a glial scar can potentially affect the quality of recordings or stimulations from implanted electrodes, it is important to determine the extent of gliosis around implants in NHP. We studied the response of cortical glial cells to chronic electrode implantation in the motor cortices of Rhesus macaques ( Macaca mulatta) after 3 months and 3 years duration. Antibodies specific for astrocytes and microglia were used to detect the presence of glial reactions around electrode implant sites. Reactive glia were found within the cortical neuropil surrounding the chronically implanted noble metal electrodes. Reactive gliosis persisted over the time periods studied and demonstrates the importance of developing strategies to minimize this event, even around noble metal implants.

Polymer-encapsulated PC-12 cells demonstrate high-affinity uptake of dopamine in vitro and 18F-DOPA uptake and metabolism after intracerebral implantation in nonhuman primates

Intracranial implantation of polymer-encapsulated PC-12 cells has been shown to improve motor behavioral performance in animal models of Parkinson's disease. The purpose of this blinded study was to examine whether such improvement is associated with the active uptake and metabolism of dopamine precursors by intracerebrally implanted polymer-encapsulated PC-12 cells. In an in vitro experiment we demonstrate that 3H-dopamine uptake by PC-12 cells was 10 8 fmol/min x 10 6 cells, and that this uptake can be specifically blocked 88% by the addition of 10 nM of nomifensine. In the in vivo experiments, polymer-encapsulated PC-12 cells were implanted in four MPTP-treated monkeys into the left deep parietal white matter (R1) or left striatum (R2–4). A fifth MPTP-treated monkey (R5) served as a control and received left striatal implants of empty capsules. 18F-Dopa Positron Emission Tomography (PET) imaging was performed on each monkey before and after implantation surgery by blinded investigators. PET images obtained 5–13 wk after implantation demonstrated well delineated focal areas of high 18F-dopa uptake in R1, R2, and R4. The focal area of high 18F-Dopa uptake in R1 precisely coregistered on a brain magnetic resonance image to the site of implantation. R3 (in whom the polymer-encapsulated PC-12 cells demonstrated poor cell survival upon explantation) and R5 (empty capsules) failed to demonstrate any area of increased 18F-dopa uptake in their PET images. Histological examination of the host brain revealed no sprouting of dopaminergic nerve terminals around the implantation sites of the polymer-encapsulated PC-12 cells. These results indicate that the previously noted behavioral improvement after intrastriatal implantation of polymer encapsulated PC-12 cells is at least in part due to their highly specific uptake and metabolism of dopamine precursors. Furthermore, these data suggest that polymer-encapsulated PC-12 cells can store, reuptake, and functionally replenish dopamine and therefore, may be an effective treatment for Parkinson's disease.

Polymer-encapsulated PC-12 cells demonstrate high-affinity uptake of dopamine in vitro and 18F-Dopa uptake and metabolism after intracerebral implantation in nonhuman primates.

Intracranial implantation of polymer-encapsulated PC-12 cells has been shown to improve motor behavioral performance in animal models of Parkinson's disease. The purpose of this blinded study was to examine whether such improvement is associated with the active uptake and metabolism of dopamine precursors by intracerebrally implanted polymer-encapsulated PC-12 cells. In an in vitro experiment we demonstrate that 3H-dopamine uptake by PC-12 cells was 10(8) fmol/min x 10(6) cells, and that this uptake can be specifically blocked 88% by the addition of 10nM of nomifensine. In the in vivo experiments, polymer-encapsulated PC-12 cells were implanted in four MPTP-treated monkeys into the left deep parietal white matter (R1) or left striatum (R2-4). A fifth MPTP-treated monkey (R5) served as a control and received left striatal implants of empty capsules. 18-F-Dopa Positron Emission Tomography (PET) imaging was performed on each monkey before and after implantation surgery by blinded investigators. PET images obtained 5-13 wk after implantation demonstrated well delineated focal areas of high 18F-dopa uptake in R1, R2, and R4. The focal area of high 18F-dopa uptake in R1 precisely coregistered on a brain magnetic resonance image to the site of implantation. R3 (in whom the polymer-encapsulated PC-12 cells demonstrated poor cell survival upon explantation) and R5 (empty capsules) failed to demonstrate any area of increased 18F-dopa uptake in their PET images. Histological examination of the host brain revealed no sprouting of dopaminergic nerve terminals around the implantation sites of the polymer-encapsulated PC-12 cells. These results indicate that the previously noted behavioral improvement after intrastriatal implantation of polymer encapsulated PC-12 cells is at least in part due to their highly specific uptake and metabolism of dopamine precursors. Furthermore, these data suggest that polymer-encapsulated PC-12 cells can store, reuptake, and functionally replenish dopamine and therefore, may be an effective treatment for Parkinson's disease.

Chronic skull-anchored percutaneous implants in non-human primates

Three groups of chronic, skull-anchored, percutaneous implants differing in materials, design and surgical procedures used for implantation, were tested in macaque monkeys in conjunction with studies of an inner ear stimulation device. Implants from the first two groups in which high-speed drilling methods and stainless steel materials were used, showed a high percentage of failures during the first 3 months after implantation of the percutaneous connector. Implants in the third group, in which measures were taken to preserve living bone tissue, all survived for greater than 7 months. Probable factors relating to implant survival are care of the bone during surgery, postsurgical mechanical trauma, materials and other details of the surgical procedure.

Osseointegration of two types of implants in nonhuman primates

Branemark developed a dental implant that can reliably replace missing teeth. The success of this implant is attributed to a direct connection of bone with the implant (osseointegration). Several implants, including the Core-Vent implant, adhere to the requirements described by Branemark and his coworkers to achieve osseointegration, yet no studies have attempted to directly compare osseointegration of the Biotes implant with other implants. This study directly compared the response of bone to the unloaded and occlusally loaded Core-Vent and Biotes implants at the light microscopic level by using the nonhuman primate model. Histologic examination revealed that both Core-Vent and Biotes implants achieved osseointegration and maintained the direct contact with bone after 5 months of occlusal loading.

Alloplastic Implants in Non-Human Primates

Refractive corneal surgery has been under investigation for more than 30 years. Although several different surgical procedures have evolved, none has gained widespread popularity. Complex technology, slow visual recovery, and lack of predictability have been some of the major problems. In an attempt to overcome these difficulties, the feasibility of corneal implants made of alloplastic materials has been tested. This paper documents the successful use of high-water content hydro-gels in non-human primates. Although these materials appear to be biologically compatible with corneal stroma, it was found that their position within the cornea was critical. Placement of these lenses at less than 50% corneal depth was universally unsuccessful, whereas placement at 50% or deeper was successful in all cases. Although stability of these materials within the cornea seems likely, the ultimate usefulness of the technique will depend on the ability to generate a predictable change in curvature at the anterior corneal surface