Biocompatibility evaluation of bioprinted decellularized collagen sheet implanted in vivo cornea using swept‐source optical coherence tomography

Corneal transplantation by full‐thickness penetrating keratoplasty with human donor tissue is a widely accepted treatment for damaged or diseased corneas. Although corneal transplantation has a high success rate, a shortage of high‐quality donor tissue is a considerable limitation. Therefore, bioengineered corneas could be an effective solution for this limitation, and a decellularized extracellular matrix comprises a promising scaffold for their fabrication. In this study, three‐dimensional bioprinted decellularized collagen sheets were implanted into the stromal layer of the cornea of five rabbits. We performed in vivo noninvasive monitoring of the rabbit corneas using swept‐source optical coherence tomography (OCT) after implanting the collagen sheets. Anterior segment OCT images and averaged amplitude‐scans were acquired biweekly to monitor corneal thickness after implantation for 1 month. The averaged cornea thickness in the control images was 430.3 ± 5.9 μm, while the averaged thickness after corneal implantation was 598.5 ± 11.8 μm and 564.5 ± 12.5 μm at 2 and 4 weeks, respectively. The corneal thickness reduction of 34 μm confirmed the biocompatibility through the image analysis of the depth‐intensity profile base. Moreover, hematoxylin and eosin staining supported the biocompatibility evaluation of the bioprinted decellularized collagen sheet implantation. Hence, the developed bioprinted decellularized collagen sheets could become an alternative solution to human corneal donor tissue, and the proposed image analysis procedure could be beneficial to confirm the success of the surgery.      

In vitro and in vivo evaluations of biodegradable implants for hormone replacement therapy: Effect of system design and PK-PD relationship

This investigation evaluated the feasibility of using subdermally implantable devices fabricated by nonconventional 3-dimensional printing technology for controlled delivery of ethinyl estradiol (EE₂). In vitro release kinetics of EE₂ and in vivo pharmacokinetics pharmacodynamics in ovariectomized New Zealand White rabbits were carried out to study 3 implant prototypes: implant I (single-channel EE₂ distribution in polycaprolactone polymer core), implant II (homogeneous EE₂ distribution in polycaprolactone polymer matrix), and implant III (concentration-gradient EE₂ distribution in polycaprolactone and poly(dl-lactide-co-glycolide) (50∶50 matrix). EE₂ was found to be released from all the implants in a nonlinear pattern with an order of implant III>implant II>implant I. The noncompartmental pharmacokinetic analysis of plasma EE₂ profiles in rabbits indicated a significant difference (p>.05) in C_max, t_max, and mean residence time between implant I and implants II and III, but no difference in the area under the plasma concentration time curves calculated by trapezoidal rule (AUC) among the implants. For pharmacodynamic studies, endogenous follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were observed to be suppressed following implantation of all implants, which demonstrated that a therapeutically effective dose of EE₂ had been delivered. Furthermore, the noncompartmental analysis of plasma FSH and LH profiles in rabbits showed a significant difference (p<.05) in AUC and the mean residence time between implant III and implants I and II. A good in vivo/in vitro relationship was observed between daily amounts of EE₂ released and plasma profiles of EE₂ for all implants. This relationship suggests that plasma profiles of EE₂ could be predicted from in vitro measurement of daily amount of EE₂ released Therefore, performing in vitro drug release studies may aid in the development of an EE₂ implant with the desired in vivo release rate. Published: September 21, 2001     

Regulation of matrix remodelling phenotype in gingival fibroblasts by substratum topography

Gingival connective tissue often has a composition resembling that of scar surrounding dental implant abutments. Increased cell adhesion, α‐smooth muscle actin (α‐SMA) expression and increased extracellular matrix deposition are a hallmark of fibrotic cells, but how topographic features influence gingival fibroblast adhesion and adoption of the α‐SMA positive myofibroblast phenotype associated with scarring is unknown. The purpose of the present study was to demonstrate whether implant topographies that limit adhesion formation would reduce myofibroblast differentiation and extracellular matrix deposition. Human gingival fibroblasts were cultured on PT (smooth) and SLA (roughened) titanium discs for varying time‐points. At 1 and 2 weeks after seeding, incorporation of α‐SMA into stress‐fibre bundles and fibronectin deposition was significantly higher on PT than SLA surfaces indicating differentiation of the cells towards a myofibroblast phenotype. Analysis of adhesion formation demonstrated that cells formed larger adhesions and more stable adhesions on PT, with more nascent adhesions observed on SLA. Gene expression analysis identified up‐regulation of 15 genes at 24 hrs on SLA versus PT associated with matrix remodelling. Pharmacological inhibition of Src/FAK signalling in gingival fibroblasts on PT reduced fibronectin deposition and CCN2 expression. We conclude that topographical features that reduce focal adhesion stability could be applied to inhibit myofibroblast differentiation in gingival fibroblasts.     

Assessing age,breeding stage,and mating activity as drivers of variation in the reproductive microbiome of female tree swallows

Sexually transmitted microbes are hypothesized to influence the evolution of reproductive strategies. Though frequently discussed in this context, our understanding of the reproductive microbiome is quite nascent. Indeed, testing this hypothesis first requires establishing a baseline understanding of the temporal dynamics of the reproductive microbiome and of how individual variation in reproductive behavior and age influence the assembly and maintenance of the reproductive microbiome as a whole. Here, we ask how mating activity, breeding stage, and age influence the reproductive microbiome. We use observational and experimental approaches to explain variation in the cloacal microbiome of free‐living, female tree swallows (Tachycineta bicolor). Using microsatellite‐based parentage analyses, we determined the number of sires per brood (a proxy for female mating activity). We experimentally increased female sexual activity by administering exogenous 17ß‐estradiol. Lastly, we used bacterial 16S rRNA amplicon sequencing to characterize the cloacal microbiome. Neither the number of sires per brood nor the increased sexual activity of females significantly influenced female cloacal microbiome richness or community structure. Female age, however, was positively correlated with cloacal microbiome richness and influenced overall community structure. A hypothesis to explain these patterns is that the effect of sexual activity and the number of mates on variation in the cloacal microbiome manifests over an individual''s lifetime. Additionally, we found that cloacal microbiome alpha diversity (Shannon Index, Faith''s phylogenetic distance) decreased and community structure shifted between breeding stages. This is one of few studies to document within‐individual changes and age‐related differences in the cloacal microbiome across successive breeding stages. More broadly, our results contribute to our understanding of the role that host life history and behavior play in shaping the cloacal microbiomes of wild birds.     

Fluocinolone acetonide intravitreal sustained release device--a new addition to the armamentarium of uveitic management

Uveitis is a potentially sight-threatening inflammatory eye disease caused by multiple infectious and non-infectious etiologies for which the standard of care involves corticosteroids or various immunomodulary therapy (IMT) drugs. These available treatments, although effective, may cause significant morbidity and sometimes mortality in uveitis patients due to their toxic side-effects and the necessity of long-term therapy to prevent recurrences. In order to avoid the systemic toxicity ofcorticosteroids and IMT or the repeated injections of local steroids necessary to control ocular inflammation, and to prevent development of cumulative damage resulting from recurrent episodes of inflammation, researchers have developed a number of local corticosteroid sustained-release devices that can be implanted directly into the vitreous of the eye, at the site of the inflammatory disease. Preliminary studies of such a device, the fluocinolone acetonide (Retisert) implant, have shown significant reductions in the number of inflammatory episodes and decreased reliance on systemic corticosteroids or other IMT. This review explores the current research evaluating the fluocinolone sustained-release intravitreal implant in the treatment of posterior uveitis and the implications for its future use on a wider scale.     

XIVE种植体即刻植入即刻负重的临床观察

目的：评价XIVE种植体在上颌外伤前牙区即刻种植即刻负重修复的临床效果。方法：对26例前牙区单颗或多颗无法保留的外伤残根拔除后,即刻植入XIVE种植体,并即刻负重修复。种植体扭矩控制在35Ncm左右,初期稳定性良好。平均四到五个月后行永久修复。在植入后1、2、4个月对其进行临床及影像学检查。结果：32枚种植体有2枚种植体2周后出现松动,一个月后脱落,其余30枚均在预期时间内形成良好骨性愈合,最终完成修复。结论：上颌前牙区单颗或多颗牙外伤,残根无法保留者,行即刻种植即刻负重修复是可行。早期种植修复有利于减缓牙槽骨的吸收,保留软硬组织的形态,缩短疗程。     

Candida biofilms on implanted biomaterials: a clinically significant problem

In recent years there has been an increasing appreciation that microbial biofilms are ubiquitous, which has resulted in a number of studies on infectious diseases from a biofilm perspective. Biofilms are defined as structured microbial communities that are attached to a surface and encased in a matrix of exopolymeric material. A wide range of biomaterials used in clinical practice have been shown to support colonization and biofilm formation by Candida spp., and the increase in Candida infections in the last decades has almost paralleled the increase and widespread use of a broad range of medical implant devices, mainly in populations with impaired host defenses. Formation of Candida biofilms has important clinical repercussions because of their increased resistance to antifungal therapy and the ability of cells within biofilms to withstand host immune defenses. Further recognition and understanding of the role of Candida biofilms in human infection should help in the clinical management of these recalcitrant infections.