Standardizing evaluation of patient-specific 3D printed models in surgical planning: development of a cross-disciplinary survey tool for physician and trainee feedback.

BACKGROUND: 3D printed models are becoming increasingly popular in healthcare as visual and tactile tools to enhance understanding of anatomy and pathology in medical trainee education, provide procedural simulation training, and guide surgical procedures. Patient-specific 3D models are currently being used preoperatively for trainee medical education in planning surgical approaches and intraoperatively to guide decision-making in several specialties. Our study group utilized a modified Delphi process to create a standardized assessment for trainees using patient-specific 3D models as a tool in medical education during pre-surgical planning. METHODS: A literature review was conducted to identify survey questions administered to clinicians in published surgical planning studies regarding the use of patient-specific 3D models. A core study team reviewed these questions, removed duplicates, categorized them, mapped them to overarching themes, and, where applicable, modified individual questions into a form generalizable across surgical specialties. The core study panel included a physician, physician-scientist, social scientist, engineer/medical student, and 3D printing lab manager. A modified Delphi process was then used to solicit feedback on the clarity and relevance of the individual questions from an expert panel consisting of 12 physicians from specialties including anesthesiology, emergency medicine, radiology, urology, otolaryngology, and obstetrics/gynecology. When the Radiological Society of North America (RSNA)/American College of Radiology (ACR) 3D Printing Registry Data Dictionary was released, additional survey questions were reviewed. A final cross-disciplinary survey of the utility of 3D printed models in surgical planning medical education was developed. RESULTS: The literature review identified 100 questions previously published in surveys assessing patient-specific 3D models for surgical planning. Following the review, generalization, and mapping of survey questions from these studies, a list of 24 questions was generated for review by the expert study team. Five additional questions were identified in the RSNA/ACR 3D Printing Registry Data Dictionary and included for review. A final questionnaire consisting of 20 questions was developed. CONCLUSIONS: As 3D printed models become more common in medical education, the need for standardized assessment is increasingly essential. The standardized questionnaire developed in this study reflects the interests of a variety of stakeholders in patient-specific 3D models across disciplines.

3-Dimensional Printed Alternative to the Standard Synthetic Flocked Nasopharyngeal Swabs Used for Coronavirus Disease 2019 Testing.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be detected in respiratory samples by real-time reverse transcriptase polymerase chain reaction (RT-PCR) or other molecular methods. Accessibility of diagnostic testing for COVID-19 has been limited by intermittent shortages of supplies required for testing, including flocked nasopharyngeal (FLNP) swabs. METHODS: We developed a 3-dimensional printed nasopharyngeal (3DP) swab as a replacement of the FLNP swab. The performance of 3DP and FLNP swabs were compared in a clinical trial of symptomatic patients at 3 clinical sites (n = 291) using 3 SARS-CoV-2 emergency use authorization tests: a modified version of the Centers for Disease Control and Prevention (CDC) RT-PCR Diagnostic Panel and 2 commercial automated formats, Roche Cobas and NeuMoDx. RESULTS: The cycle threshold-C(t)-values from the gene targets and the RNase P gene control in the CDC assay showed no significant differences between swabs for both gene targets (P = .152 and P = .092), with the RNase P target performing significantly better in the 3DP swabs (P < .001). The C(t) values showed no significant differences between swabs for both viral gene targets in the Roche cobas assay (P = .05 and P = .05) as well as the NeuMoDx assay (P = .401 and P = .484). The overall clinical correlation of COVID-19 diagnosis between all methods was 95.88% (Kappa 0.901). CONCLUSIONS: The 3DP swabs were equivalent to standard FLNP in 3 testing platforms for SARS-CoV-2. Given the need for widespread testing, 3DP swabs printed onsite are an alternate to FLNP that can rapidly scale in response to acute needs when supply chain disruptions affect availability of collection kits.

The promise and challenges of stem cell-based therapies for skeletal diseases: stem cell applications in skeletal medicine: potential, cell sources and characteristics, and challenges of clinical translation.

Despite decades of research, remaining safety concerns regarding disease transmission, heterotopic tissue formation, and tumorigenicity have kept stem cell-based therapies largely outside the standard-of-care for musculoskeletal medicine. Recent insights into trophic and immune regulatory activities of mesenchymal stem cells (MSCs), although incomplete, have stimulated a plethora of new clinical trials for indications far beyond simply supplying progenitors to replenish or re-build lost/damaged tissues. Cell banks are being established and cell-based products are in active clinical trials. Moreover, significant advances have also been made in the field of pluripotent stem cells, in particular the recent development of induced pluripotent stem cells. Their indefinite proliferation potential promises to overcome the limited supply of tissue-specific cells and adult stem cells. However, substantial hurdles related to their safety must be overcome for these cells to be clinically applicable.

Development of a Survey Tool: Understanding the Patient Experience With Personalized 3D Models in Surgical Patient Education.

BACKGROUND: Three-dimensional (3D) printing has been increasingly utilized in the healthcare sector for many applications including guiding surgical procedures, creating medical devices, and producing custom prosthetics. As personalized medicine becomes more accessible and desired, 3D printed models emerge as a potential tool in providing patient-specific education. These personalized 3D models are at the intersection of technological innovation and medical education. Our study group utilized a modified Delphi process to create a comprehensive survey tool assessing patient experience with personalized 3D models in preoperative education. METHODS: A rigorous literature review was conducted of prior patient education survey tools in surgical cases across specialties involving personalized 3D printed models. Through categorization and mapping, a core study team reviewed individual questions, removed duplicates, and edited them into generalizable form. A modified Delphi process was then used to solicit feedback on question clarity and relevance from both 3D printing healthcare experts and patients to create a final survey.  Results: 173 survey questions from the literature were evaluated by the core study team, yielding 31 unique questions for further review. After multiple rounds of feedback, a final survey containing 18 questions was developed.  Conclusion: 3D printed models have the potential to be helpful tools in surgical patient education, and there exists a need to standardize the assessment of patient experience with these models. This survey provides a standardized, generalizable way to investigate the patient experience with personalized 3D-printed models.

From the ground up: understanding the developing infrastructure and resources of 3D printing facilities in hospital-based settings.

BACKGROUND: 3D printing is a popular technology in many industries secondary to its ability to rapidly produce inexpensive, high fidelity models/products, mainly through layer-by-layer fusion of various substrate materials. In healthcare, 3D printing has garnered interest for its applications in surgery, simulation, education, and medical device development, and 3D printing facilities are now being integrated into hospital-based settings. Yet, little is known regarding the leadership, resources, outputs, and role of these new onsite entities. METHODS: The purpose of this research was to survey features of North American hospital-based 3D printing facilities to understand their design and utility in anticipation of future expansion. Hospital-based 3D printing labs were recruited through online special interest groups to participate via survey response. Anonymous, voluntary data were collected from 21 facilities over 9 weeks and reported/analyzed in aggregate. RESULTS: Of the respondents, > 50% were founded in the past 5 years and 80% in the past decade, indicating recent and rapid growth of such facilities. Labs were most commonly found within large, university-affiliated hospitals/health systems with administration frequently, but not exclusively, through radiology departments, which was shown to enhance collaboration. All groups reported collaborating with other medical specialties/departments and image segmentation as part of the workflow, showing widespread interest in high fidelity, personalized medicine applications. Lab leadership was most often multidisciplinary, with physicians present on nearly all leadership teams. Budgets, personnel, and outputs varied among groups, however, all groups reported engagement in multiple 3D printing applications. CONCLUSION: This preliminary study provides a foundation for understanding the unique nature of hospital-based 3D printing labs. While there is much to learn about such in-house facilities, the data obtained reveal important baseline characteristics. Further research is indicated to validate these early findings and create a detailed picture of the developing infrastructure of 3D printing in healthcare settings.

Printing the Pathway Forward in Bone Metastatic Cancer Research: Applications of 3D Engineered Models and Bioprinted Scaffolds to Recapitulate the Bone-Tumor Niche.

Breast cancer commonly metastasizes to bone, resulting in osteolytic lesions and poor patient quality of life. The bone extracellular matrix (ECM) plays a critical role in cancer cell metastasis by means of the physical and biochemical cues it provides to support cellular crosstalk. Current two-dimensional in-vitro models lack the spatial and biochemical complexities of the native ECM and do not fully recapitulate crosstalk that occurs between the tumor and endogenous stromal cells. Engineered models such as bone-on-a-chip, extramedullary bone, and bioreactors are presently used to model cellular crosstalk and bone-tumor cell interactions, but fall short of providing a bone-biomimetic microenvironment. Three-dimensional bioprinting allows for the deposition of biocompatible materials and living cells in complex architectures, as well as provides a means to better replicate biological tissue niches in-vitro. In cancer research specifically, 3D constructs have been instrumental in seminal work modeling cancer cell dissemination to bone and bone-tumor cell crosstalk in the skeleton. Furthermore, the use of biocompatible materials, such as hydroxyapatite, allows for printing of bone-like microenvironments with the ability to be implanted and studied in in-vivo animal models. Moreover, the use of bioprinted models could drive the development of novel cancer therapies and drug delivery vehicles.

Lubricin distribution in the human intervertebral disc.

BACKGROUND: Previous studies have identified lubricin (also known as superficial zone protein) as a lubricating glycoprotein present in several musculoskeletal tissues including articular cartilage, meniscus, and tendon. In this immunohistochemical study, we determined the presence and distribution of lubricin in the cells, extracellular matrix, and tissue surfaces of human nucleus pulposus and anulus fibrosus tissues. METHODS: Twenty-eight human intervertebral discs were resected at autopsy from fourteen cadavers. Disc specimens were fixed in formalin, processed, and paraffin-embedded prior to sectioning. Tissue sections were immunohistochemically stained for lubricin, the extent of extracellular matrix staining was evaluated semiquantitatively, and cellular staining was assessed quantitatively with use of a survey method. RESULTS: Lubricin staining was evident in the extracellular matrix and at select surfaces of the nucleus pulposus and anulus fibrosus tissues. The extent of lubricin staining of the extracellular matrix was contingent on the disc region (nucleus pulposus, inner anulus fibrosus, or outer anulus fibrosus), with the greatest extent of matrix staining found in the nucleus pulposus, but it was not contingent on the Thompson grade. A subset of disc cells within the nucleus, inner anulus, and outer anulus also stained positively for lubricin, suggesting intrinsic cell synthesis of the glycoprotein. The disc region significantly affected the percentage of lubricin-staining cells, with the greatest percentage of cells staining for lubricin (nearly 10%) found in the nucleus pulposus. The percentage of cells staining for lubricin correlated with the extent of extracellular matrix staining for lubricin. CONCLUSIONS: The results of this study confirm the presence of lubricin in the human intervertebral disc and demonstrate a unique distribution compared with that in the goat. The presence of lubricin in asymptomatic discs provides a foundation for future research regarding the role of lubricin in pathological disc conditions.

The presence and distribution of lubricin in the caprine intervertebral disc.

Lubricin is a large, multifunctional glycoprotein that is known to play a role as a boundary lubricant in diarthrodial joint articulation. The hypothesis of this study was that lubricin is present in the intervertebral disc in a distribution consistent with serving to facilitate interlamellar tribology. The objectives were to: (1) determine the distribution of lubricin in the normal caprine disc; and (2) investigate the synthesis of lubricin by caprine annulus fibrosus (AF) and nucleus pulposus (NP) cells in vitro, using immunohistochemical methods. Caprine lumbar intervertebral discs from five levels and four animals were studied. Positive staining revealed the presence of the lubricin in the outer AF of nearly all samples. No staining was present in the inner AF or the NP. Within the outer AF, lubricin was prominent in the layers separating lamellae and in the extracellular matrix of the lamellae. Some of the AF cells within the lubricin-positive regions demonstrated intracellular lubricin staining, suggesting that these cells may be synthesizing the lubricin protein observed. Immunohistochemistry performed on monolayer cultures of primary AF and NP cells demonstrated intracellular lubricin staining in both cell types. Thus, lubricin is selectively present in the outer caprine intervertebral disc AF, and its distribution suggests that it may play a role in interlamellar tribology. Cells from both the annulus and nucleus were found capable of synthesizing lubricin in vitro, suggesting that these cells may be a potential source of the glycoprotein under some conditions.