Patient-specific Implants Improve Volumetric Surgical Accuracy Compared to Stock Reconstruction Plates in Modern Pardigm Virtual Surgical Planning of Fibular Free Flaps for Head and Neck Reconstruction.

BACKGROUND: Virtual surgical planning (VSP) for composite microvascular free flaps has become standard of care for oncologic head and neck reconstruction. Controversy remains as to the use of three-dimensional (3D)-printed titanium patient-specific implants (PSIs) versus hand-bent stock reconstruction plates. Proponents of PSIs cite improved surgical accuracy, reduced operative times, and improved clinical outcomes. Detractors purport increased cost associated with PSIs and presumed equivalent accuracy with less expensive stock plates. PURPOSE: The study purpose was to measure and compare the 3D-volumetric accuracy of PSI versus stock reconstruction plates among subjects undergoing VSP-guided mandibular fibular free flap reconstruction. STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study of subjects undergoing VSP-guided fibular free flap reconstructions at Mayo Clinic between 2016 and 2023 was performed. Subjects were excluded for non-VSP guidance, midfacial reconstruction, nonfibular free flaps, and lack of requisite study variables. PREDICTOR VARIABLE: The primary predictor was the type of reconstruction plate utilized (PSI vs stock plate). MAIN OUTCOME VARIABLE: The main outcome was volumetric surgical accuracy of the final reconstruction compared to the preoperative surgical plan by root mean square error (RMSE) calculation. Lower RMSE values indicated a higher surgical accuracy. COVARIATES: Covariates included age, sex, race, smoking status, American Society of Anesthesiologists Physical Status Classification System, Charlson Comorbidity Index, preoperative diagnosis, and number of fibular segments. ANALYSES: Differences in surgical accuracy were assessed between preoperative and postoperative segmented scans using volumetric overlays from which RMSE values were calculated. Univariate and multivariate modeling of plate type to RMSE calculation was performed. Statistical significance set to P < .05. RESULTS: Total of 130 subjects were identified, 105 PSI and 25 stock plates. Calculated mean RMSE in millimeters (mm) for stock plates was 1.46 (standard deviation: 0.33) and 1.15 (standard deviation: 0.36) for PSIs. Univariate modeling demonstrated a statistically significant difference in RMSE of 0.31 (95% confidence interval: 0.16-0.47) (P < .001) equating to a 21.2% (P < .001) improved volumetric surgical accuracy for PSIs. The association of improved volumetric accuracy with PSIs has been maintained in all multivariate models controlling for confounding. CONCLUSION AND RELEVANCE: In modern era VSP-guided head and neck fibular free flap reconstruction, patient-specific 3D-printed titanium implants confer a statistically significant improvement in volumetric surgical accuracy over stock reconstruction plates.

Three-dimensional printing accuracy analysis for medical applications across a wide variety of printers.

Purpose: Three-dimensional (3D) printing has had a significant impact on patient care. However, there is a lack of standardization in quality assurance (QA) to ensure printing accuracy and precision given multiple printing technologies, variability across vendors, and inter-printer reliability issues. We investigated printing accuracy on a diverse selection of 3D printers commonly used in the medical field. Approach: A specially designed 3D printing QA phantom was periodically printed on 16 printers used in our practice, covering five distinct printing technologies and eight different vendors. Longitudinal data were acquired over six months by printing the QA phantom monthly on each printer. Qualitative assessment and quantitative measurements were obtained for each printed phantom. Accuracy and precision were assessed by comparing quantitative measurements with reference values of the phantom. Data were then compared among printer models, vendors, and printing technologies; longitudinal trends were also analyzed. Results: Differences in 3D printing accuracy across printers were observed. Material jetting and vat photopolymerization printers were found to be the most accurate. Printers using the same 3D printing technology but from different vendors also showed differences in accuracy, most notably between vat photopolymerization printers from two different vendors. Furthermore, differences in accuracy were found between printers from the same vendor using the same printing technology, but different models/generations. Conclusions: These results show how factors such as printing technology, vendor, and printer model can impact 3D printing accuracy, which should be appropriately considered in practice to avoid potential medical or surgical errors.

Construction and Validation of a Benchtop Model for Testing of Mechanical Thrombectomy Devices for Pulmonary Embolism.

PURPOSE: This study aims to define the process of designing and manufacturing 3D printed and glass models of the pulmonary artery (PA) and utilizing them in a test bed for evaluation of devices for mechanical thrombectomy of pulmonary embolism (PE). MATERIALS AND METHODS: Patient derived computed tomography angiography (CTA) images of the PA were digitally converted into a hollowed-out structure and translated into clear 3D printed and glass models. A test bed was created using a peristaltic pump and silicone tubing connected to the models. Human clot analogs were then prepared and injected within the models. Thrombectomy testing was done using clinically used predicates and baseline characteristics of the models were evaluated by independent interventionalists. RESULTS: The mean sizes of the main pulmonary artery (MPA) for the 3D printed model and glass model were 30.4 mm and 29.2 mm, mimicking those of the patient's PA obtained on CTA. Heterogeneous human clot analogs were created with fibrin composition ranging from 60 to 30%. Mechanical thrombectomy was successfully attempted by independent interventionalists. Both the 3D printed, and glass model were appraised as very good for multiple attributes. CONCLUSION: A complete test bed using 3D printed and glass models of the PA with human clot analogs was created for testing of mechanical thrombectomy devices for PE.

Establishing a Point-of-Care Virtual Planning and 3D Printing Program.

Virtual surgical planning (VSP) and three-dimensional (3D) printing have become a standard of care at our institution, transforming the surgical care of complex patients. Patient-specific, anatomic models and surgical guides are clinically used to improve multidisciplinary communication, presurgical planning, intraoperative guidance, and the patient informed consent. Recent innovations have allowed both VSP and 3D printing to become more accessible to various sized hospital systems. Insourcing such work has several advantages including quicker turnaround times and increased innovation through collaborative multidisciplinary teams. Centralizing 3D printing programs at the point-of-care provides a greater cost-efficient investment for institutions. The following article will detail capital equipment needs, institutional structure, operational personnel, and other considerations necessary in the establishment of a POC manufacturing program.

Impact of mesenchymal stem cell-secretome-loaded hydrogel on proliferative and migratory activities of hyperglycemic fibroblasts.

Disruption of the reparative process, often found in diabetic patients, results in chronic, non-healing wounds that significantly impact a patient's quality of life. This highlights the need of new therapeutic options to improve the healing of diabetic wounds. In this study, we focused on developing a cell-free hydrogel dressing loaded with mesenchymal stem cell (MSC)-conditioned media (CM) to potentially improve the healing of hard-to-heal wounds. We simulated a hyperglycemic environment by incubating human dermal fibroblasts in a high glucose environment (30 mM) and validated that MSC-CM rescued the impaired functions (proliferation and migration) of hyperglycemic fibroblasts. Further, we investigated the effect of loading MSC-CM in gelatin methacrylate (GelMA)-poly (ethylene glycol) diacrylate (PEGDA) hybrid hydrogels in improving the proliferative activity of glucose-treated fibroblasts. The controlled release of bioactive factors from MSC-CM loaded GelMA-PEGDA hydrogels promoted the metabolic activity of hyperglycemic fibroblasts. In addition, the growth rate of hyperglycemic fibroblasts was found to be similar to that of normal fibroblasts. Our observations, thus, suggest the potential application of cell-free, MSC-secretome-loaded hydrogel in the healing of diabetic or chronic wounds.

Harnessing mesenchymal stem cell secretome: Effect of extracellular matrices on proangiogenic signaling.

The low engraftment and retention rate of mesenchymal stem cells (MSCs) at the target site indicates that the potential benefits of MSC-based therapies can be attributed to their paracrine signaling. In this study, the extracellular matrices (ECMs) deposited by bone marrow-derived human MSCs in the presence and absence of ascorbic acid was characterized. MSCs were seeded on top of decellularized ECM (dECM) and the concentrations of proangiogenic and antiangiogenic molecules released in culture (conditioned) media was compared. Effects of ECM derived from MSCs with different passage numbers on MSC secretome was also investigated. Our study revealed that the expression of proangiogenesis-related factors were upregulated when MSCs were harvested on dECMs, irrespective of media supplementation, as compared with those cultured on tissue culture plates. In addition, dECM generated in the presence of ascorbic acid promoted the expression of proangiogenic molecules as compared with dECM-derived in absence of media supplementation. Further, it was observed that the effectiveness of dECM to stimulate proangiogenic signaling of MSCs was reduced as cell passage number was increased from P3 to P5. The proliferation as well as capillary morphogenesis of human umbilical vein endothelial cells (HUVECs) in the presence of conditioned media were enhanced compared with the normal HUVECs culture media. These data indicate that the secretory signatures of MSCs and consequently, the therapeutic efficacy of MSCs can be regulated by presentation of dECM composition and variation of its composition.

Evaluation of cystatin C as an early biomarker of cadmium nephrotoxicity in the rat.

Cadmium (Cd) is a nephrotoxic environmental pollutant that causes insidious injury to the proximal tubule that results in severe polyuria and proteinuria. Cystatin C is a low molecular weight protein that is being evaluated as a serum and urinary biomarker for various types of ischemic and nephrotoxic renal injury. The objective of the present study was to determine if cystatin C might be a useful early biomarker of Cd nephrotoxicity. Male Sprague-Dawley rats were given daily injections of Cd for up to 12 weeks. At 3, 6, 9 and 12 weeks, urine samples were analyzed for cystatin C, protein, creatinine, ß2 microglobulin and kidney injury molecule-1. The results showed that Cd caused a significant increase in the urinary excretion of cystatin C that occurred 3-4 weeks before the onset of polyuria and proteinuria. Serum levels of cystatin C were not altered by Cd. Immunolabeling studies showed that Cd caused the relocalization of cystatin C from the cytoplasm to the apical surface of the epithelial cells of the proximal tubule. The Cd-induced changes in cystatin C labelling paralleled those of the brush border transport protein, megalin, which has been implicated as a mediator of cystatin C uptake in the proximal tubule. These results indicate that Cd increases the urinary excretion of cystatin C, and they suggest that this effect may involve disruption of megalin-mediated uptake of cystatin C by epithelial cells of the proximal tubule.