Applied use of biomechanical measurements from human tissues for the development of medical skills trainers: a scoping review.

OBJECTIVE: The objective of this review was to identify quantitative biomechanical measurements of human tissues, the methods for obtaining these measurements, and the primary motivations for conducting biomechanical research. INTRODUCTION: Medical skills trainers are a safe and useful tool for clinicians to use when learning or practicing medical procedures. The haptic fidelity of these devices is often poor, which may be because the synthetic materials chosen for these devices do not have the same mechanical properties as human tissues. This review investigates a heterogeneous body of literature to identify which biomechanical properties are available for human tissues, the methods for obtaining these values, and the primary motivations behind conducting biomechanical tests. INCLUSION CRITERIA: Studies containing quantitative measurements of the biomechanical properties of human tissues were included. Studies that primarily focused on dynamic and fluid mechanical properties were excluded. Additionally, studies only containing animal, in silico , or synthetic materials were excluded from this review. METHODS: This scoping review followed the JBI methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Sources of evidence were extracted from CINAHL (EBSCO), IEEE Xplore, MEDLINE (PubMed), Scopus, and engineering conference proceedings. The search was limited to the English language. Two independent reviewers screened titles and abstracts as well as full-text reviews. Any conflicts that arose during screening and full-text review were mediated by a third reviewer. Data extraction was conducted by 2 independent reviewers and discrepancies were mediated through discussion. The results are presented in tabular, figure, and narrative formats. RESULTS: Data were extracted from a total of 186 full-text publications. All of the studies, except for 1, were experimental. Included studies came from 33 countries, with the majority coming from the United States. Ex vivo methods were the predominant approach for extracting human tissue samples, and the most commonly studied tissue type was musculoskeletal. In this study, nearly 200 unique biomechanical values were reported, and the most commonly reported value was Young's (elastic) modulus. The most common type of mechanical test performed was tensile testing, and the most common reason for testing human tissues was to characterize biomechanical properties. Although the number of published studies on biomechanical properties of human tissues has increased over the past 20 years, there are many gaps in the literature. Of the 186 included studies, only 7 used human tissues for the design or validation of medical skills training devices. Furthermore, in studies where biomechanical values for human tissues have been obtained, a lack of standardization in engineering assumptions, methodologies, and tissue preparation may implicate the usefulness of these values. CONCLUSIONS: This review is the first of its kind to give a broad overview of the biomechanics of human tissues in the published literature. With respect to high-fidelity haptics, there is a large gap in the published literature. Even in instances where biomechanical values are available, comparing or using these values is difficult. This is likely due to the lack of standardization in engineering assumptions, testing methodology, and reporting of the results. It is recommended that journals and experts in engineering fields conduct further research to investigate the feasibility of implementing reporting standards. REVIEW REGISTRATION: Open Science Framework https://osf.io/fgb34.

Phenotypic and functional characterization of herpes simplex virus glycoprotein B epitope-specific effector and memory CD8+ T cells from symptomatic and asymptomatic individuals with ocular herpes.

UNLABELLED: Herpes simplex virus 1 (HSV-1) glycoprotein B (gB)-specific CD8(+) T cells protect mice from herpes infection and disease. However, whether and which HSV-1 gB-specific CD8(+) T cells play a key role in the "natural" protection seen in HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. In this study, we have dissected the phenotypes and the functions of HSV-1 gB-specific CD8(+) T cells from HLA-A*02:01 positive, HSV-1 seropositive ASYMP and symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpes disease). We found the following. (i) Healthy ASYMP individuals maintained a significantly higher proportion of differentiated HSV-1 gB-specific effector memory CD8(+) T cells (TEM cells) (CD45RA(low) CCR7(low) CD44(high) CD62L(low)). In contrast, SYMP patients had frequent less-differentiated central memory CD8(+) T cells (TCM cells) (CD45RA(low) CCR7(high) CD44(low) CD62L(high)). (ii) ASYMP individuals had significantly higher proportions of multifunctional effector CD8(+) T cells which responded mainly to gB342-350 and gB561-569 "ASYMP" epitopes, and simultaneously produced IFN-γ, CD107(a/b), granzyme B, and perforin. In contrast, effector CD8(+) T cells from SYMP individuals were mostly monofunctional and were directed mainly against nonoverlapping gB17-25 and gB183-191 "SYMP" epitopes. (iii) Immunization of an HLA-A*02:01 transgenic mouse model of ocular herpes with "ASYMP" CD8(+) TEM cell epitopes, but not with "SYMP" CD8(+) TCM cell epitopes, induced a strong CD8(+) T cell-dependent protective immunity against ocular herpes infection and disease. Our findings provide insights into the role of HSV-specific CD8(+) TEM cells in protection against herpes and should be considered in the development of an effective vaccine. IMPORTANCE: A significantly higher proportion of differentiated and multifunctional HSV-1 gB-specific effector memory CD8(+) T cells (TEM cells) (CD45RA(low) CCR7(low) CD44(high) CD62L(low)) were found in healthy ASYMP individuals who are seropositive for HSV-1 but never had any recurrent herpetic disease, while there were frequent less-differentiated and monofunctional central memory CD8(+) T cells (TCM cells) (CD45RA(low) CCR7(high) CD44(low) CD62L(high)) in SYMP patients. Immunization with "ASYMP" CD8(+) TEM cell epitopes, but not with "SYMP" CD8(+) TCM cell epitopes, induced a strong protective HSV-specific CD8(+) T cell response in HLA-A*02:01 transgenic mice. These findings are important for the development of a safe and effective T cell-based herpes vaccine.