Use Of Cadaveric Tissue Research Articles

Clinical applications of bioengineered tissue-cellular products for management of corneal diseases.

To discuss bioengineered tissue-cellular products for treatment of corneal diseases that are currently in clinical use. These include tissue-cellular products that have received regulatory approval, are being used off-label in clinical practice, or are in active use in clinical trials. Due to the global shortage of donor corneal tissue, significant efforts have been made to develop bioengineering tissue-cellular products that can replace or augment the use of cadaveric tissue for corneal transplantation. The development of carrier substrates to support transplantation of cultivated limbal epithelial transplantation (CLET) has been a growing area of research. CLET offers a promising therapeutic alternative to conventional simple limbal epithelial transplantation and keratolimbal allografts for treatment of limbal stem cell deficiency. Engineered tissue matrices and porcine-derived corneas are potential alternatives to human donor tissue in anterior lamellar keratoplasty for corneal ulcers and scars, as well as intrastromal transplants for advanced keratoconus. For endothelial disease, substrate supported cultured endothelial cell grafts, and synthetic barrier devices are promising alternative to traditional endothelial keratoplasties. There has been increasing interest in cellular and acellular bioengineered tissue-cellular and synthetic products for treatment of corneal diseases, and many of these products have already seen clinical use. Industry and academia have important roles in advancing these products to later phase clinical trials and comparing them to conventional allograft approaches. Future development of full thickness donor corneas with cultivated epithelium, endothelium, and stromal keratocytes in a biosynthetic matrix will likely be an important next step in tissue alternatives. Continued progress in this field will be critical for addressing the global disease burden from corneal blindness.

Improving the Accuracy of Maxillary Sinus Balloon Dilation Using Virtual Reality Navigation: A Proof-of-Concept Study.

The ability to reliably and accurately cannulate the natural ostium of the maxillary sinus during balloon sinus dilation (BSD) has been criticized. Conventional computed tomography (CT)-guided navigation systems are helpful when dilating other sinuses, but they fail to provide meaningful feedback to guide accurate dilation of the maxillary sinus. This study explores the potential impact of a new navigation system with virtual reality (VR) functionality on successful BSD of the maxillary sinus. Using the established methodology, a cadaveric evaluation of the accuracy of maxillary BSD with a VR-equipped navigation system and balloon was undertaken. The natural ostium was landmarked on CT images with a beacon, and a VR intrasinus camera view was used to guide balloon dilation by a team of 2 rhinologists. Following the procedure, uncinectomies were performed to directly assess the accuracy of dilation. Standardized video clips with a 30° endoscopic view of the area were reviewed by 3 blinded rhinologists from different institutions who were not part of the procedures. Dilation of the natural ostium was scored as "successful," "unsuccessful," or "unsure." Sixteen maxillary BSDs were completed in 8 cadavers using VR navigation. The medial wall of the maxillary sinus showing the natural ostium as well as any accessory ostia were readily visualized and labeled with a beacon in all cases using the 3D virtual rendering feature. Dilations were scored using a standardized rubric. Any "unsure" responses from the reviewers were categorized as "unsuccessful" for analysis purposes. The accuracy rate for dilation of the maxillary sinus natural ostium was 77%. Despite the use of cadaveric tissues, a fair interrater agreement (kappa 0.21) was achieved. Using VR navigation appears to improve the accuracy of cannulating the natural ostium during maxillary BSD, which could lead to better outcomes. Further study in live subjects is warranted.

Surgical Simulation Maximizing the Use of Fresh-Frozen Cadaveric Specimens: Examination of Tissue Integrity Using Ultrasound.

Arthroscopic surgical simulation, including the use of cadaveric tissue, is valuable for training orthopedic surgery residents. However, it is unclear how often fresh-frozen cadaveric tissue can be reused to provide a reproducible model for developing arthroscopic skills. We determined the usefulness of ultrasound in evaluating tissue degradation in fresh-frozen shoulder and knee joints used for surgical simulation. Between February 7 and April 11, 2017, orthopedic residents participated in 6 wet lab sessions during 1 rotation. Knee and shoulder specimens were subjected to ultrasound using a SonoSite Edge machine and a linear probe after each freeze-and-thaw cycle. Degradation of each structure was determined based on standards created for living tissue and comparisons to previous images of the same tissue before initial use. Ultrasonographic assessment of the 2 knee and 2 shoulder specimens revealed lost integrity in subcutaneous fat and muscle with evidence of increased hypoechoicity and loss of normal fiber orientation and density in all specimens examined. Tendons, ligaments, cartilage, iliotibial band, and bone did not lose integrity during freezing and thawing. Ultrasonographic assessment revealed no loss of joint structure integrity. However, the intra-articular work assigned for the simulation curriculum had been carried out to a degree that by the third use, little opportunity remained for further arthroscopic practice on that specimen. In this study, ultrasound findings showed that fresh-frozen shoulder and knee specimens maintained structural integrity useful for simulation training after 3 cycles of freezing.

Repeatability of digital image correlation for measurement of surface strains in composite long bones

Digital image correlation (DIC) can measure full-field surface strains during mechanical testing of hard and soft tissues. When compared to traditional methods, such as strain gauges, DIC offers larger validation data (∼50,000 points) for, e.g., finite element models. Our main aim was to evaluate the repeatability of surface strain measurements with DIC during compressive testing of composite femurs mimicking human bones. We also studied the similarity of the composite femur samples using CT. Composite femurs were chosen as test material to minimize the uncertainties associated with the use of cadaveric tissues and to understand the variability of the DIC measurement itself. Six medium-sized fourth generation composite human proximal femora (Sawbones) were CT imaged and mechanically tested in stance configuration. The force–displacement curves were recorded and the 3D surface strains were measured with DIC on the anterior surface of the femurs. Five femurs fractured at the neck–trochanter junction and one at the site below the minor trochanter. CT image of this bone showed an air cavity at the initial fracture site. All femurs fractured through a sudden brittle crack. The fracture force for the composite bones was 5751±650N (mean±SD). The maximum von Mises strain during the fractures was 2.4±0.8%. Noise in one experiment was 5–30µε. When applied loads were equalized the variation in strains between the bones was 20–25%, and when the maximum strains were equalized, variation in the other regions was 5–10%. DIC showed that the ability of nominally identical composite bones to bear high strains and loads before fracturing may vary between the samples.

Taking DNA from the dead

Using cadaveric specimens in genome research presents many benefits: investigators can study multiple organs from one individual, including those impossible to collect from living donors (for example, brains), and health risks are minimized as the individual is deceased. Several genomic research initiatives plan to collect cadaveric tissues. For instance, the Genotype-Tissue Expression (GTEx) project, a US National Institutes of Health Roadmap initiative, is seeking insights into the mechanics of gene regulation by identifying variations in gene expression that are highly correlated with genetic variation (1). Another example is the Allen Institute for Brain Science's human brain atlases, which seek to create a comprehensive three-dimensional map of gene expression in the human brain (2). However, in many countries, including the United States, there are not adequate ethical guidelines in place for this type of research. Scandals involving the removal and retention of organs from cadavers in the United Kingdom led to enactment of the Human Tissue Act, which makes it a crime to conduct genome research using tissues from cadavers without consent (3). In the United States, cadaveric specimens can be obtained and used for most research with little regulatory oversight, no ethical review and without informed consent. Deceased individuals are not human subjects under US federal regulations (4). Although the Revised Uniform Anatomical Gift Act recommends that states require individual or family permission to retain cadaveric tissues for use in research (5), permission is not the same as providing informed consent. When an anatomical gift is made, only the purpose of the gift is specified (for example, transplantation, therapy, research, or education); no discussion of the nature of the research or its risks, benefits and alternatives is required. However, ethically, individuals retain certain interests after death, including an interest in having their bodies treated with respect and in having their ante-mortem wishes upheld (6). Living individuals whose organs may be used for research post-mortem may also suffer present harm in anticipation that their corpse will be treated in ways that violate their values or beliefs. Also, family members (whether genetically related or not) have an interest in the disposition of a loved one's remains. Finally, the use of cadaveric tissues in genome research raises additional ethical concerns about privacy. Some have argued that deceased individuals can suffer nonexperiential harm, such as loss of reputation that may result from a privacy breach after death (6), and close genetic relatives have privacy interests that deserve protection (7). Research has shown that DNA is a unique identifier (8, 9), and in some forensic cases it has been used to identify the biological relatives of a suspect (10). For these reasons, it is recommended that research on the newly dead is subjected to independent ethical review and that informed consent is obtained from the individual before death or from the legally authorized surrogate (7, 11). The informed consent process should be integrated into existing organ procurement processes to allow priority to be given to transplanting viable organs and to avoid duplicate requests, and it should include an explanation of the potential privacy risks for the sample source, as well as her or his close genetic relatives. In addition, precautions should be taken to protect privacy by limiting access to DNA data through restricted databases (12). However, independent informed consent from genetic relatives should not be required because the risks are extremely small in relation to the burdens that such a requirement would impose on research. DNA will only reveal predictive information about biological relatives, and the risk of identifiability is both uncertain and dependent upon the nature of the data and the degree of relatedness to the sample source. Further, in most cases it would be impracticable to identify and locate all potentially affected relatives, and the contact itself might constitute a breach of privacy. Further research will be needed to ensure that new policies are responsive to the concerns and perspectives of potential donors and their families. In the absence of data regarding public perspectives, we recommend a preventative ethics approach that involves institutional review board appraisal and informed consent from the individual or a surrogate. This approach may prevent future scandals and bolster public trust. At the same time, it is not overly burdensome and so should not significantly impede research.

A protocol system for testing biohazardous materials in an impact biomechanics research facility.

This article presents a protocol system, comprised of a review process and a series of checklists, that was developed for testing cadaveric tissue in an impact biomechanics research facility. The use of cadaveric tissue may expose personnel to bloodborne pathogens including HIV and hepatitis B, which have been shown to remain virulent in a cadaver for several weeks after death. To minimize exposure risks, the protocol system presented emphasizes initial blood screening to keep infectious tissue from entering the laboratory, and adopts universal precautions to prevent exposure by treating all tissue as though it were infected. All lab employees must read, sign, and demonstrate proficiency in the protocol. Well-developed test procedures for the handling of biohazardous materials along with an annual individual protocol review have proven effective for the past 6 years in minimizing exposure risks.