Implantation In Animal Model Research Articles

Does an Osteoporosis-like Condition Jeopardize the Osseointegration Process around Dental Implants Placed in Animal Models? A Systematic Review.

Knowing that osteoporosis is a metabolic disease that could decrease dental implant success and survival, the purpose of this review was to gather information on the characteristics of implant osseointegration in animal models of induced osteoporosis. By pointing out the role of some factors that could improve the success rate in these situations, this study aimed to enhance the knowledge about this process that can be further translated to clinical designs. A systematic search in PubMed/Medline, Lilacs, Cochrane Library, Scopus and Web of Science was conducted to identify information between 2002 and 2023 regarding osseointegration of dental implants in animal models of induced osteoporosis. The following search strategy was utilized and adjusted to each database: (((dental implant) AND (Osseointegration)) AND (osteoporosis)) AND/OR (osteoporosis treatment). The inclusion criteria were animal studies in English, involving the placement of an osseointegrated implant in osteoporotic bone, and evaluating bone to implant contact (BIC) %. Exclusion criteria were studies in humans, in vitro studies, procedures involving any kind of bone graft and studies evaluating medication related osteonecrosis of the jaw. A standardized data extraction form was used to record data for each study, covering article title, date, authors, number of animals, purpose of study, type of analysis used by authors, follow-up, type of implant, test and control groups, intervention and conclusions. The risk of bias of the included studies was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) Risk of Bias tool.20 Results: A total of 204 articles were found for evaluation and selection. All of the 43 selected studies evaluated the bone-implant contact (BIC) %. Other parameters such as bone to implant mechanical interface, bone area (BA) and bone volume (BV) ratio were also evaluated in some of the studies. There was a tendency for compromised results of implant osseointegration in the presence of osteoporosis. Modification of the implant surface, systemic and local use of anti-resorptive drugs and other substances, showed benefits for the implant success in osteoporotic sites. Still, no consensus among studies on the superiority of systemic medications in improving the process of peri-implant bone repair, was observed. Although it is possible to improve the osseointegration of implants in osteoporotic bone, either by using systemic or local factors, the metabolic bone syndrome caused by osteoporosis can jeopardize the osseointegration of dental implants.

A novel porous hydroxyapatite scaffold (pHAMG) enhances angiogenesis and osteogenesis around dental implants by regulating the immune microenvironment.

The purpose was to evaluate whether a novel porous hydroxyapatite (HA) scaffold with a 25-30-µm groove structure (pHAMG) may improve bone osteogenesis, angiogenesis, and bone integration of titanium dental implants in animal models. The pHAMG was prepared by chemical precipitation method and its elemental composition and crystal structure were evaluated. The ability of the scaffolds to induce ectopic osteogenesis and the ability of scaffolds combined with titanium dental implants to induce orthotopic peri-implant angiogenesis, osteogenesis, and osteointegration were tested after implantation into the femur muscle pocket in rats and the mandibular defects in beagle dogs, respectively. The elemental composition was evaluated by SEM-EDS; the expression of the relevant osteogenic/inflammation marker and the anti-/pro-inflammation markers was evaluated by immunostaining and immunofluorescence, respectively. In animal experiments with ectopic and peri-implant osteogenesis, pHAMG resulted in significantly larger neovascularization by hematoxylin-eosin staining, as well as deposition of collagen fibers by Masson staining than HA. Meanwhile, microgrooves in pHAMG upregulate more bone morphogenetic protein (BMP) 2 and interleukin-4 (IL-4) and -10 (IL-10) and downregulate more IL-1β and tumor necrosis factor-α (TNF-α) than that in HA. The pHAMG showed greater expression of arginase (Arg)-1 and lower expression of inducible nitric oxide synthase (iNOS) than HA. The novel pHAMG can better repair bone defects in ectopic and orthotopic model. It also transfers macrophages to anti-inflammatory phenotypes, promoting angiogenic and osteogenesis in scaffolds, and bone integration in implants. The novel pHAMG induce greater osteogenesis and angiogenesis which could be utilized in the clinical treatment.

OR2803 Corticotroph Fate Weighted Cell Differentiation Paradigm For Human Induced Pluripotent Stem Cells

Abstract Disclosure: M.E. Moore: None. K.G. Chen: None. K. Park: None. D. Asuzu: None. N. Ramavenkat: None. S. Walbridge: None. D. Mullaney: None. M. Arhin: None. D. Maric: None. D. Mandal: None. P. Chittiboina: None. Introduction: The vertebrate anterior pituitary gland is a highly conserved ‘master’ organ that controls hormonal milieu in real-time. Pituitary adenomas and their treatments (surgery, chemotherapy or radiation) can result in pituitary organ failure, specifically hypocortisolism, a challenging condition to manage. Here, we created an optimized paradigm (anterior pituitary corticotroph or APcor) to preferentially drive human induced pluripotent stem cells (hiPSCs) towards a pituitary corticotroph fate. Methods: We directed U112I hiPSCs towards terminally differentiated cell types using a combination of rho-associated kinase inhibitor (Y-27632), bone morphogenic protein 4 (BMP4), transforming growth factor β inhibitor (SB431542), sonic hedgehog (SHH), fibroblast growth factor 8b (FGF8b), fibroblast growth factor 10 (FGF10) and leukemia inhibitory factor (LIF). Markers for pluripotent stem cells, cranial placode (CP), Rathke’s Pouch (RP), anterior pituitary progenitors and mature cell types were assessed at 10-day intervals using quantitative qRT-PCR and multiplex immunocytochemistry (mICC) or immunohistochemistry (IHC). ACTH activity was measured using ELISA (MD Bio). Results: We tested initial differentiation conditions and found optimal CP initiation in presence of SB431542. We observed decrease in embryonic stem cell markers OCT4 and NANOG by day 10, with concomitant increase in CP/RP markers SIX1, PAX6 and SIX6 using mICC/IHC and qRT-PCR. Continuation of differentiation paradigm with LIF showed strong expression of anterior pituitary progenitor markers PITX1, TBX19 and POU1F1 at day 20. pRT-PCR analysis at this time point confirms differentiation towards pituitary cell types without needing enrichment for SIX1. At day 30, POMC expression was observed by IHC in 10-15% of cells as measured by quantitative analysis (Qupath 0.2.0), indicating mature corticotrophs. Corticotroph cell fate was confirmed with corticotropin releasing hormone (CRH) stimulation which led to up to 40x-fold increase in ACTH expression detected by ELISA (D30 w/CRH vs Pluripotent w/CRH). Conclusions: We found with the APcor paradigm, we can reliably drive towards corticotroph cell fate. We successfully differentiated hiPSCs into mature functioning corticotrophs with ability to recapitulate pituitary organ function. Our method is amenable to 3D organoid formation and pre-clinical implantation in animal models of hypophysectomy as a novel hormone replacement therapy. Presentation: Sunday, June 18, 2023

3D Bioprinting in Otolaryngology: A Review.

The evolution of tissue engineering and 3D bioprinting has allowed for increased opportunities to generate musculoskeletal tissue grafts that can enhance functional and aesthetic outcomes in otolaryngology-head and neck surgery. Despite literature reporting successes in the fabrication of cartilage and bone scaffolds for applications in the head and neck, the full potential of this technology has yet to be realized. Otolaryngology as a field has always been at the forefront of new advancements and technology and is well poised to spearhead clinical application of these engineered tissues. In this review, current 3D bioprinting methods are described and an overview of potential cell types, bioinks, and bioactive factors available for musculoskeletal engineering using this technology is presented. The otologic, nasal, tracheal, and craniofacial bone applications of 3D bioprinting with a focus on engineered graft implantation in animal models to highlight the status of functional outcomes in vivo; a necessary step to future clinical translation are reviewed. Continued multidisciplinary efforts between material chemistry, biological sciences, and otolaryngologists will play a key role in the translation of engineered, 3D bioprinted constructs for head and neck surgery.

Bone Marrow-Derived Mesenchymal Stem Cell Implants for the Treatment of Focal Chondral Defects of the Knee in Animal Models: A Systematic Review and Meta-Analysis.

Osteoarthritis remains an unfortunate long-term consequence of focal cartilage defects of the knee. Associated with functional loss and pain, it has necessitated the exploration of new therapies to regenerate cartilage before significant deterioration and subsequent joint replacement take place. Recent studies have investigated a multitude of mesenchymal stem cell (MSC) sources and polymer scaffold compositions. It is uncertain how different combinations affect the extent of integration of native and implant cartilage and the quality of new cartilage formed. Implants seeded with bone marrow-derived MSCs (BMSCs) have demonstrated promising results in restoring these defects, largely through in vitro and animal studies. A PRISMA systematic review and meta-analysis was conducted using five databases (PubMed, MEDLINE, EMBASE, Web of Science, and CINAHL) to identify studies using BMSC-seeded implants in animal models of focal cartilage defects of the knee. Quantitative results from the histological assessment of integration quality were extracted. Repair cartilage morphology and staining characteristics were also recorded. Meta-analysis demonstrated that high-quality integration was achieved, exceeding that of cell-free comparators and control groups. This was associated with repair tissue morphology and staining properties which resembled those of native cartilage. Subgroup analysis showed better integration outcomes for studies using poly-glycolic acid-based scaffolds. In conclusion, BMSC-seeded implants represent promising strategies for the advancement of focal cartilage defect repair. While a greater number of studies treating human patients is necessary to realize the full clinical potential of BMSC therapy, high-quality integration scores suggest that these implants could generate repair cartilage of substantial longevity.

Lessons learned from pre-clinical testing of xenogeneic decellularized esophagi in a rabbit model

SummaryDecellularization of esophagi from several species for tissue engineering is well described, but successful implantation in animal models of esophageal replacement has been challenging. The purpose of this study was to assess feasibility and applicability of esophageal replacement using decellularized porcine esophageal scaffolds in a new pre-clinical model. Following surgical replacement in rabbits with a vascularizing muscle flap, we observed successful anastomoses of decellularized scaffolds, cues of early neovascularization, and prevention of luminal collapse by the use of biodegradable stents. However, despite the success of the surgical procedure, the long-term survival was limited by the fragility of the animal model. Our results indicate that transplantation of a decellularized porcine scaffold is possible and vascular flaps may be useful to provide a vascular supply, but long-term outcomes require further pre-clinical testing in a different large animal model.

Preservation of corneal stromal lenticule: review.

Corneal stromal lenticule is a part of corneal stroma, which can be created by manual dissection, by femtosecond laser from the donor cornea, but chiefly it is a waste product of a refractive procedure ReLex SMILE (Small Incision LenticuleExtraction). Corneal lenticule has a huge potential in corneal surgery. In recent years, many studies have been published to show the possibility to use this tissue to treat corneal defects, as well as in refractive surgery. Thanks to the quantity of lenticules which arise every day during SMILE operations, this tissue is much more accessible than any other kind of corneal tissue. According to the experience with lenticule implantation in animal models, or even human patients, lenticule implantation is considered safe, reversible method, which is not associated with immune rejection or other severe complications. However, the crucial step before the process of lenticule implantation, is proper preservation of this tissue. Donor corneal tissue containing endothelium is usually preserved in hypothermia and then usable maximally for two weeks. Newer methods such as organ culture storage and use of a sterile cornea prolong the time of usability of the tissue. The possibilities for corneal lenticule storage are theoretically wider thanks to the fact, that we do not need to preserve fragile cellular structures. Besides the storage in hypothermia, other preserving methods such as cryopreservation and storage after decellularization have been tested. This review aimed to examine the current literature that describes possible methods of corneal lenticule preservation. A comprehensive search was created based on articles published in English on PubMed.gov, Cochranelibrary.com and Scopus.com using following keywords: corneal lenticule preservation, corneal lenticule storage, cold storage corneal lenticule, corneal lenticule cryopreservation till 2020.

Preclinical in vivo research of magnesium-based implants for fracture treatment: A systematic review of animal model selection and study design

Degradable magnesium implants are promising for clinical fracture treatment, providing less stress-shielding mechanical support and superior bone-strengthening benefits to traditional materials. The quality of preclinical research is essential for developing Mg implants; however, there are considerable variations in the model selection and study design in published studies, posing challenges for safe and effective clinical translation of lab discoveries. The purpose of this systematic review is to investigate the current progress on in vivo research of Mg implants for fracture treatment, focusing on model selection, Mg materials, implant design, methodological and analyzing techniques, aiming to provide comprehensive guidance for future preclinical research. PubMed and Embase online databases were searched to identify researches investigating Mg implants in animal models of fracture from 1960 to December 2019, using a combination of keywords: magnesium and fracture. Eligible studies were included without language restriction. Data extraction was conducted for qualitative analysis. Meta-analysis was not performed due to extensive heterogeneities among studies. Twenty studies published from 2014 to 2019 were included. Publication information, animal model, methodological quality, implants preparation, and evaluation techniques were extracted. The methodological assessment revealed low to high risk of bias among studies. Both rodent and non-rodent species were selected, and the anatomical sites for inducing fractures included both cranial-facial and limb bones. Pure Mg and alloys with or without surface modification were evaluated, covering implant designs of both intra-medullary and extra-medullary fixation. Radiological and histological evaluations were commonly conducted. Published in vivo evidence confirmed the role of Mg-based implants in promoting fracture healing. However, considering heterogeneity in animal selection, implant preparation, and evaluation methods, there still lacks a standardized reference model. By analyzing the information extracted from included studies, the systematic review may facilitate planning and conducting preclinical research with translational perspective.

Effects of the local administration of antibiotics on bone formation around dental implants in animal models: a systematic review and meta‐analysis

Effects of the local administration of antibiotics on bone formation around dental implants in animal models: a systematic review and meta‐analysis

The role of VEGF and BMP-2 in stimulation of bone healing with using hybrid bio-composite scaffolds coated implants in animal model

BackgroundOsteogenesis and angiogenesis are two closely correlated processes during bone growth, development, remodeling, and repair. Vascular endothelial growth factor (VEGF) is an essential mediator during the process of angiogenesis. The bone morphogenetic protein (BMP-2) family of growth factors plays critical roles in bone formation. VEGF has the potential to enhance BMPs-induced bone formation.PurposeThis study attempted to assess VEGF and BMP-2 reflecting the effect of hybrid bio-composite scaffold on bone healing in dogs and evaluate the quality of the healing process radiologically.MethodsThis study was conducted on 12 adult mongrel dogs. All dogs were divided into four equal groups (n = 3 each): chitosan non-medicated (CH) (NM), chitosan medicated (CH) (M), chitosan bioglass non-medicated (CH.BG) (NM), and Chitosan Bioglass Medicated (CH.BG) (M). VEGF and BMP-2 were evaluated during fracture healing.ResultsResults have showed a non-significant decrease in serum VEGF activity in the (CH.BG) (M) group when compared to other groups during 2, 3 weeks, followed by gradual decrease, then increase at 12 weeks of interval period. There was highly significant increase from pre-surgery to 12 weeks in serum BMP-2 levels in the (CH.BG) (M) group when compared to other groups.ConclusionBiochemical parameters along with clinical and radiographical provide sound knowledge on the degree of bone healing with the use of chitosan bio-glass medicated by risedronate sodium drug. The statistical analysis will include the Fisher exact test and T test with significance level P < 0.05 (AU).Graphical abstract

Photofunctionalization as a suitable approach to improve the osseointegration of implants in animal models-A systematic review and meta-analysis.

To determine whether photofunctionalization influences dental implant osseointegration. Data on osseointegration rates were extracted from 8 databases, based on bone-to-implant contact (BIC) and pushout tests. Internal validity was accessed through the SYRCLE risk of bias tool for animal experimental studies. Meta-analyses were performed for investigation of the influence of photofunctionalization on implant osseointegration, with a random effect and a confidence interval of 95%. The certainty of evidence was accessed through the GRADE approach. Thirty-four records were identified, and 10 were included in the meta-analysis. Photofunctionalized implants showed higher mean values for BIC in rabbits (MD 6.92 [1.01, 12.82], p=.02), dogs (MD 23.70 [10.23, 37.16], p=.001), rats (MD 20.93 [12.91, 28.95], p<.0001), and in the pooled BIC analyses (MD 14.23 [7.80, 20.66], p<.0001) compared to those in control implants in the overall assay. Conversely, at late healing periods, the pooled BIC meta-analyses showed no statistically significant differences (p>.05) for photofunctionalized and control implants at 12weeks of follow-up. For pushout analysis, photofunctionalized implants presented greater bone strength integration (MD 19.92 [13.88, 25.96], p<.0001) compared to that of control implants. The heterogeneity between studies ranged from "not important" to "moderate" for rabbits I2 =24%, dogs I2 =0%, rats I2 =0%, and pooled BIC (I2 =49%), while considerable heterogeneity was observed for pushouts (I2 =90%). Photofunctionalization improves osseointegration in the initial healing period of implants, as summarized from available data from rabbit, dog, and rat in vivo models.

Glucocorticoid for Hearing Preservation After Cochlear Implantation: A Systemic Review and Meta-analysis of Animal Studies

To conduct systematic review and meta-analyses of preclinical studies describing the efficacy of glucocorticoids administered via different routes for hearing preservation after cochlear implantation. A literature search was performed in PubMed to identify peer-reviewed articles published before December 31, 2017, with no language restrictions. Search components were "Cochlear implant," "Glucocorticoids," and "Hearing preservation." The results were specified for animal studies. Original studies in which glucocorticoids were administered before or during cochlear implantation in animal models and hearing threshold shifts were measured using auditory brainstem response. Quality of included studies was assessed using the SYstematic Review Centre for Laboratory animal Experimentation protocol. Threshold Shift reduction between the "study" and "control" groups at 1-month postimplantation was the parameter used to evaluate hearing preservation. The random-effects models were used to combine the results of selected studies. Separate meta-analyses were performed for drug-eluting electrodes, systemic, and local administration. Administering either systemic or topical glucocorticosteroids had a significant effect on preserving low and high-frequency hearing. Topical administration was equally effective across a range of concentration levels and provided maximal hearing preservation when applied 120 minutes before implantation. The effect of systemic treatment was achieved with high doses, equivalent to 26 mg of dexamethasone per day in humans. No significant effect was found with the use of drug-eluting electrodes and more studies are needed to characterise the utility and efficacy of this administration method.

Manganese dioxide coating reduces bacterial adhesion and infection in silicon implants in animal model.

To propose a new coating to silicone implants using Manganese dioxide. We present bacterial adhesion and proliferation when implants are challenged with Escherichia coli. Coated and control silicon implants were placed in two independent subcutaneous pouches in the dorsum of Wistar rats. After skin closure, 0.5ml of E. coli solution was injected in each incision. The animals were euthanized at 7 and 28days. Extracted material was cultured and analyzed by confocal microscopy. At 1week, uncoated implants had a 17-fold higher infection rate (p < 0.001). Coated samples showed a mean bacterial count of 28,700CFU/ml, while the control ones 503,000CFU/ml, with a significant mean difference of 474,300CFU/ml (95% CI 165,900-782,600). At 4weeks, the mean bacterial growth in coated group was 7600; while in control one was 53,890. The mean difference between groups was 46,200 (95% CI 21,100-71,400). Confocal microscopy presented the percentage of implant's surface with attached bacteria: at 7days, coated implants had 6.85% and controls 10.9% and the difference was not significant (p =0.32). At 4weeks, the coated group showed 0.98% of the surface with attached bacteria, while control group showed 7.64%, which resulted in a significant 11-fold difference (p = 0.004). Manganese dioxide coating inhibits bacterial proliferation and adhesion in subcutaneous silicon implants in an animal model. These findings can be useful to improve development of biomaterials.

Comparison of Clinical Results and Pathological Examinations Between Locally Synthesized Bone-derived Hydroxyapatite and Medpor® Orbital Implants in Animal Models.

We aimed to compare clinical and pathological reactions towards locally synthesized bovine bone derived from hydroxyapatite (bone docosahexaenoic acid (dHA)) and commercially available porous polyethylene (Medpor®, Porex Surgical Incorporation, Georgia, USA) orbital implants in animal models. An experimental study was performed on 14 New Zealand white rabbits. Group A (n=7) was implanted with bovine bone dHA and group B (n=7) was implanted with Medpor®. Clinical examinations were performed on Days 1, 7, 14, 28, and 42 post-implantation. The implanted eyes were enucleated on Day 42 and were sent for pathological evaluation. Serial clinical examinations included urine color and odor; feeding and physical activity demonstrated normal wellbeing in all the subjects. Localized minimal infection was observed in both groups during the first two weeks following implantation, and the subjects responded well to topical moxifloxacin. Both groups exhibited evidence of wound breakdown. No signs of implant migration or extrusion were observed in either group. The histopathological examination revealed no statistically significant difference in inflammatory cell reactions and fibrovascular tissue maturation between both types of implants. However, all (100%) of the bovine bone dHA implants displayed complete fibrovascular ingrowth compared to Medpor® implants (57.1%) at six weeks post-implantation (p=0.001). In conclusion, bovine bone dHA and Medpor® orbital implants were well-tolerated clinically and displayed similar inflammatory reactions and fibrovascular tissue maturation. Locally synthesized bovine bone dHA orbital implants displayed significantly greater complete fibrovascular ingrowth in comparison with Medpor® implants.

Preclinical Evaluation of Mesh Implants: The Pathologist's Perspective.

Surgical and laparoscopic implantation of mesh devices is on the rise for a variety of applications. The complexity and range of evolving mesh designs calls for consistent and detailed pathologic evaluation in determining host responses and assessing overall safety. This review addresses the components of evaluation of mesh implants in animal models, with emphasis on histologic parameters, semiquantitative scoring matrices, and morphometric analyses that have been specifically adapted to this class of implants. Necropsy assessment should include implant persistence, architecture, and associated host responses such as exudation and adhesions. Microscopic evaluation should focus on primary relevant responses such as bioresorption, integration/tissue ingrowth, neovascularization, and inflammation. Selection of the best means of processing and evaluation can be complicated, as meshes may include one or more biologic components (e.g., collagen), synthetic polymer fibers, coatings, and other molecules. The architecture of some meshes can influence tissue responses and complicate sampling, sectioning, and evaluation. Recognition of specific study objectives and knowledge of anticipated responses helps to determine the appropriate histologic or immunochemical stains, while understanding of mesh composition and anticipated persistence in tissue determines the suitability of paraffin or resin embedding, and both guide the evaluation of mesh devices in the preclinical setting.

Effects of Local Drug and Chemical Compound Delivery on Bone Regeneration Around Dental Implants in Animal Models: A Systematic Review and Meta-Analysis.

One of the suggested methods for enhancing osseointegration is the local application of drug agents around implant surfaces. The aim of this review was to evaluate the methods most commonly used for local drug and chemical compound delivery to implant sites and assess their influence on osseointegration. An electronic search was undertaken in three databases (PubMed, Scopus, Embase). The search was limited to animal experiments using endosseous implants combined with local drug delivery systems. Meta-analyses were performed for the outcome bone-to-implant contact (BIC). Sixty-one studies met the inclusion criteria. Calcium phosphate (CaP), bisphosphonates (BPs), and bone morphogenetic proteins (BMPs) were the most commonly used chemical compounds. There were two main methods for local drug delivery at the bone-implant interface: (1) directly from an implant surface by coating or immobilizing techniques, and (2) the local application of drugs to the implant site, using carriers. There was a statistically significant increase in BIC for both local drug delivery methods (P = .02 and P < .0001, respectively) compared with the control methods. There was a statistically significant increase in BIC when CaP (P = .0001) and BMPs (P = .02) were either coating implants or were delivered to the implant site, in comparison to when drugs were not used. The difference was not significant for the use of BPs (P = .15). It is suggested that the use of local chemical compound delivery systems around implants could significantly improve implant osseointegration in animal models. It is a matter of debate whether these in vivo results might have some significant effect in the human clinical setting in the long term.

Detrimental effects of alcohol exposure around conception: putative mechanisms.

In western countries, alcohol consumption is widespread in women of reproductive age, and in binge quantities. These countries also continue to have high incidences of unplanned pregnancies, with women often reported to cease drinking after discovering their pregnancy. This suggests the early embryo may be highly exposed to the detrimental effects of alcohol during the periconception period. The periconception and pre-implantation windows, which include maturation of the oocyte, fertilisation, and morphogenesis of the pre-implantation embryo, are particularly sensitive times of development. Within the oviduct and uterus, the embryo is exposed to a unique nutritional environment to facilitate its development and establish de-novo expression of the genome through epigenetic reprogramming. Alcohol has wide-ranging effects on cellular stress, as well as hormonal, and nutrient signalling pathways, which may affect the development and metabolism of the early embryo. In this review, we summarise the adverse developmental outcomes of early exposure to alcohol (prior to implantation in animal models) and discuss the potential mechanisms for these outcomes that may occur within the protected oviductal and uterine environment. One interesting candidate is reduced retinoic acid synthesis, as it is implicated in the control of epigenetic reprogramming and cell lineage commitment, processes that have adverse consequences for the formation of the placenta, and subsequently, fetal programming.

Automated and High-Throughput Reactive Accelerated Aging System to Evaluate Performance of Neural Implants

Explosive growth of therapeutic applications for neuromodulation is partly associated with miniaturization of neural implants. Miniaturization is implemented with novel fabrication techniques and novel materials that do not have a proven history of clinical use. Pilot clinical studies with these novel devices demonstrated that failure of the implants in the body and their poor lifetime presents a major bottleneck for this technology. Lifetime evaluation of different neural implants in animal models requires very long endpoints to establish their viability on clinically relevant timescales. To accelerate testing of innovative materials and potentially replace chronic animal testing, we developed reactive accelerated aging (RAA) that uses reactive oxygen species to simulate foreign body response. The first version of the RAA system accurately represented degradation mechanisms of these devices, but required daily monitoring and maintenance and experienced some variability in performance. To address these issues, we developed a new system that implements automation, modularity and multiplexing. First, we designed the RAA system to be scalable and modular to facilitate multiplexing for high-throughput testing. Second, we replaced the thermostats with mineral oil thermal transfer with electrical heating. Third, we implemented automatic control of hydrogen peroxide concentration using an in-line UV spectrophotometer. Fourth, through using a Raspberry Pi we are able to perform in situ optimization of operating parameters and increased control of the system. These improvements will enable us to perform experiments in parallel for a high-throughput approach to investigating optimal test conditions for different materials or device geometries. Lastly, we implemented automatic sampling and analysis of leachable compounds to establish and quantify neural implants failure modes. Through these improvements, we developed a cost-effective tool for rapid evaluation of durability of neural implants in vitro and provide the framework to improve the functional lifespan of these devices. Studies performed using this technique to rapidly age cortical implants has been compared to those performed in vivo in a feline model performed at University of Utah. Results of this comparison using scanning electron microscopy characterization show similarities between aging implants for 7 days in vitro (RAA) to aging implants for over 3 years in vivo (feline).

Evaluating the osseointegration of nanostructured titanium implants in animal models: Current experimental methods and perspectives (Review).

The aim of this paper is to review the experimental methods currently being used to evaluate the osseointegration of nanostructured titanium implants using animal models. The material modifications are linked to the biocompatibility of various types of oral implants, such as laser-treated, acid-etched, plasma-coated, and sand-blasted surface modifications. The types of implants are reviewed according to their implantation site (endoosseous, subperiosteal, and transosseous implants). The animal species and target bones used in experimental implantology are carefully compared in terms of the ratio of compact to spongy bone. The surgical technique in animal experiments is briefly described, and all phases of the histological evaluation of osseointegration are described in detail, including harvesting tissue samples, processing undemineralized ground sections, and qualitative and quantitative histological assessment of the bone-implant interface. The results of histological staining methods used in implantology are illustrated and compared. A standardized and reproducible technique for stereological quantification of bone-implant contact is proposed and demonstrated. In conclusion, histological evaluation of the experimental osseointegration of dental implants requires careful selection of the experimental animals, bones, and implantation sites. It is also advisable to use larger animal models and older animals with a slower growth rate rather than small or growing experimental animals. Bones with a similar ratio of compact to spongy bone, such as the human maxilla and mandible, are preferred. A number of practical recommendations for the experimental procedures, harvesting of samples, tissue processing, and quantitative histological evaluations are provided.

In vivo response to polypropylene following implantation in animal models: a review of biocompatibility

Introduction and hypothesisPolypropylene is a material that is commonly used to treat pelvic floor conditions such as pelvic organ prolapse (POP) and stress urinary incontinence (SUI). Owing to the nature of complications experienced by some patients implanted with either incontinence or prolapse meshes, the biocompatibility of polypropylene has recently been questioned. This literature review considers the in vivo response to polypropylene following implantation in animal models. The specific areas explored in this review are material selection, impact of anatomical location, and the structure, weight and size of polypropylene mesh types.MethodsAll relevant abstracts from original articles investigating the host response of mesh in vivo were reviewed. Papers were obtained and categorised into various mesh material types: polypropylene, polypropylene composites, and other synthetic and biologically derived mesh.ResultsPolypropylene mesh fared well in comparison with other material types in terms of host response. It was found that a lightweight, large-pore mesh is the most appropriate structure.ConclusionThe evidence reviewed shows that polypropylene evokes a less inflammatory or similar host response when compared with other materials used in mesh devices.