Regulatory Considerations in the Design and Manufacturing of Implantable 3D‐Printed Medical Devices

Three‐dimensional (3D) printing, or additive manufacturing, technology has rapidly penetrated the medical device industry over the past several years, and innovative groups have harnessed it to create devices with unique composition, structure, and customizability. These distinctive capabilities afforded by 3D printing have introduced new regulatory challenges. The customizability of 3D‐printed devices introduces new complexities when drafting a design control model for FDA consideration of market approval. The customizability and unique build processes of 3D‐printed medical devices pose unique challenges in meeting regulatory standards related to the manufacturing quality assurance. Consistent material powder properties and optimal printing parameters such as build orientation and laser power must be addressed and communicated to the FDA to ensure a quality build. Postprinting considerations unique to 3D‐printed devices, such as cleaning, finishing and sterilization are also discussed. In this manuscript we illustrate how such regulatory hurdles can be navigated by discussing our experience with our group's 3D‐printed bioresorbable implantable device.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115990/1/cts12315.pd

Dimensions of the medial wall of the prelacrimal recess

BACKGROUND: Addressing anterior maxillary sinus pathology endoscopically that is inaccessible with an endoscopic modified medial maxillectomy requires either a prelacrimal approach (PLA) or an endoscopic Denker\u27s approach (EDA). The PLA involves removing the medial wall of the prelacrimal recess (PLR), which is the bone between the pyriform aperture (PA) and nasolacrimal duct (NLD), from nasal floor to orbital floor. The PLA preserves the inferior turbinate and NLD, whereas both are sacrificed during an EDA. The purpose of this computed tomography (CT)-based study was to determine the anteroposterior and superoinferior dimensions of the medial wall of the PLR. METHODS: One hundred thirty-one triplanar sinus CT scans of patients with various rhinologic diseases, but with intact bony PLR walls, were reviewed to assess dimensions of the medial wall of the PLR. The anteroposterior distances from the PA to the inferior-most, middle, and superior-most aspects of the NLD were measured. The height from the nasal floor to orbital floor was also measured. Combining left and right sides, there were 262 measurements. RESULTS: The anteroposterior distances between the PA and the NLD were as follows: inferior: mean, 8.4 mm (standard error [SE], 0.2; range, 1.9-14.2); middle: mean, 7.6 mm (SE, 0.2; range, 0-13.6); and superior: mean, 5.5 mm (SE, 2.5; range, 0-11.9). The mean height of the medial wall of the PLR was 26.5 mm (SE, 0.2; range, 18.5-39.9). CONCLUSION: The anteroposterior and superoinferior dimensions of the medial wall of the PLR are variable, with the anteroposterior dimension being widest inferiorly. Its dimensions should be evaluated preoperatively when considering endoscopic approaches to or through the anterior maxillary sinus

Analysis of patient factors associated with 30‐day mortality after tracheostomy

OBJECTIVE: Mortality has been reported to be 22% to 45% in patients with a tracheostomy. To better counsel patients and families, we aimed to determine the effect of body mass index (BMI), socioeconomic status (SES), and the 17 conditions of the Charlson comorbidity index (CCI) on 30-day survival posttracheostomy. METHODS: This retrospective cohort study identified adult patients enrolled from our institution in the Global Tracheostomy Collaborative database from March 2014 to June 2015. Data collected included age, BMI, residential zip code, and comorbidities. Cox proportionate univariate and multivariate analyses were used to measure the impact of BMI, SES, and CCI variables with 30-day posttracheostomy survival. We used geocoding as a surrogate for patients\u27 SES. We used Deyo\u27s modification of the CCI, which utilized International Classification of Diseases, 9th Revision, codes to identify comorbidities. RESULTS: Of 326 tracheostomies identified, the 30-day mortality rate was 15.6%. No significant differences were noted in BMI or in any of the SES categories between survivors and nonsurvivors. CCI was significantly higher in the 30-day mortality group. Congestive heart failure (hazard ratio [HR] = 2.39), severe liver disease (HR = 3.15), and peripheral vascular disease (HR = 2.62) were found to significantly impact 30-day survival. CONCLUSION: Higher CCI and specifically severe liver disease, congestive heart failure, and peripheral vascular disease were associated with increased 30-day mortality posttracheostomy. No association was found between BMI or SES and 30-day survival. This study identified three comorbidities that independently affect mortality in tracheostomy patients, which should be discussed with patients and families before tracheostomy. LEVEL OF EVIDENCE: 3 Laryngoscope, 129:847-851, 2019

Co-culture of adipose-derived stem cells and chondrocytes on three-dimensionally printed bioscaffolds for craniofacial cartilage engineering

OBJECTIVES/HYPOTHESIS: Reconstruction of craniofacial cartilagenous defects are among the most challenging surgical procedures in facial plastic surgery. Bioengineered craniofacial cartilage holds immense potential to surpass current reconstructive options, but limitations to clinical translation exist. We endeavored to determine the viability of utilizing adipose-derived stem cell-chondrocyte co-culture and three-dimensional (3D) printing to produce 3D bioscaffolds for cartilage tissue engineering. We describe a feasibility study revealing a novel approach for cartilage tissue engineering with in vitro and in vivo animal data. METHODS: Porcine adipose-derived stem cells and chondrocytes were isolated and co-seeded at 1:1, 2:1, 5:1, 10:1, and 0:1 experimental ratios in a hyaluronic acid/collagen hydrogel in the pores of 3D-printed polycaprolactone scaffolds to form 3D bioscaffolds for cartilage tissue engineering. Bioscaffolds were cultured in vitro without growth factors for 4 weeks and then implanted into the subcutaneous tissue of athymic rats for an additional 4 weeks before sacrifice. Bioscaffolds were subjected to histologic, immunohistochemical, and biochemical analysis. RESULTS: Successful production of cartilage was achieved using a co-culture model of adipose-derived stem cells and chondrocytes without the use of exogenous growth factors. Histology demonstrated cartilage growth for all experimental ratios at the post-in vivo time point confirmed with type II collagen immunohistochemistry. There was no difference in sulfated-glycosaminoglycan production between experimental groups. CONCLUSION: Tissue-engineered cartilage was successfully produced on 3D-printed bioresorbable scaffolds using an adipose-derived stem cell and chondrocyte co-culture technique. This potentiates co-culture as a solution for several key barriers to a clinically translatable cartilage tissue engineering process. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E251-E257, 2018

Co‐culture of adipose‐derived stem cells and chondrocytes on three‐dimensionally printed bioscaffolds for craniofacial cartilage engineering

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145213/1/lary27200.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145213/2/lary27200_am.pd