Design of medical tympanostomy conduits with selective fluid transport properties.

Implantable tubes, shunts, and other medical conduits are crucial for treating a wide range of conditions from ears and eyes to brain and liver but often impose serious risks of device infection, obstruction, migration, unreliable function, and tissue damage. Efforts to alleviate these complications remain at an impasse because of fundamentally conflicting design requirements: Millimeter-scale size is required to minimize invasiveness but exacerbates occlusion and malfunction. Here, we present a rational design strategy that reconciles these trade-offs in an implantable tube that is even smaller than the current standard of care. Using tympanostomy tubes (ear tubes) as an exemplary case, we developed an iterative screening algorithm and show how unique curved lumen geometries of the liquid-infused conduit can be designed to co-optimize drug delivery, effusion drainage, water resistance, and biocontamination/ingrowth prevention in a single subcapillary-length-scale device. Through extensive in vitro studies, we demonstrate that the engineered tubes enabled selective uni- and bidirectional fluid transport; nearly eliminated adhesion and growth of common pathogenic bacteria, blood, and cells; and prevented tissue ingrowth. The engineered tubes also enabled complete eardrum healing and hearing preservation and exhibited more efficient and rapid antibiotic delivery to the middle ear in healthy chinchillas compared with current tympanostomy tubes, without resulting in ototoxicity at up to 24 weeks. The design principle and optimization algorithm presented here may enable tubes to be customized for a wide range of patient needs.

A Systematic Review of Nonautologous Graft Materials Used in Human Tympanoplasty.

OBJECTIVES: Nonautologous graft materials may solve several dilemmas in tympanoplasty by obviating the need for graft harvest, facilitating consistent wound healing, and permitting graft placement in the clinical setting. Prior studies of nonautologous grafts in humans have shown variable outcomes. In this systematic review, we aim to 1) summarize clinical outcomes and 2) discuss limitations in the literature regarding nonautologous grafts for tympanoplasty in humans. METHODS: A literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The study size, etiology and duration of perforation, type of nonautologous graft, and postoperative closure rate were assessed. RESULTS: The PRISMA approach yielded 61 articles, including 3,247 ears that met inclusion criteria. Studies evaluated nonautologous grafts including paper patch, gelatin sponge, growth factors, porcine small-intestinal submucosa, among others. Traumatic perforations (62.3%) were most commonly studied, whereas postinfectious perforations (31.9%) and other etiologies (5.8%) comprised a minority of cases. Acute perforations of <8 weeks duration constituted just over half of all treated ears. Overall closure rate was 82.1%, with significantly higher closure rates in acute (89.9%) versus chronic perforations (64.9%, P < .01), regardless of material. A median postoperative air-bone gap of 5.6 dB was found in the 23% of studies reporting this metric. CONCLUSIONS: The majority of publications reviewing nonautologous materials in tympanoplasty evaluate acute or traumatic perforations, and few rigorously report hearing outcomes. Given available data, porcine submucosa and basic fibroblast growth factor may hold promise for chronic perforation closure. Future studies should report closure rates and hearing outcomes in perforations >8 weeks duration. Laryngoscope, 131:392-400, 2021.

High-Frequency Conductive Hearing following Total Drum Replacement Tympanoplasty.

OBJECTIVES: Conventional reporting of posttympanoplasty hearing outcomes use a pure-tone averaged air-bone gap (ABG) largely representing a low-frequency sound conduction. Few studies report high-frequency conductive hearing outcomes. Herein, we evaluate high-frequency ABG in patients following temporalis fascia total drum replacement. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: All patients who underwent type 1 tympanoplasty using a lateral graft total drum replacement technique between August 2016 and February 2019 were identified. Patients with pre- and postoperative audiograms were included. Low-frequency ABG was calculated as the mean ABG at 250, 500, and 1000 Hz. High-frequency ABG was calculated at 4 KHz. Pre- and postoperative ABGs were compared. RESULTS: Twenty-three patients were included, and the mean age at surgery was 44 years (range, 9-68 years). Perforation etiology was from trauma (n = 14) or chronic otitis media (n = 9). Preoperative mean low-frequency ABG was 27.8 ± 12.6 dB and mean high-frequency ABG was 21.5 ± 15.1 dB (P = .044). Postoperatively, the mean low-frequency ABG was significantly reduced by 15.5 ± 13.3 dB (P < .001) while the mean high-frequency ABG insignificantly changed (reduced by 2.6 ± 16.2 dB, P = .450). CONCLUSION: In a series of patients undergoing temporalis fascia total drum replacement, low-frequency ABG improved; however, high-frequency conductive hearing loss persists. Conventional methods of reporting ABG may not identify persistent high-frequency ABG. These results merit further study across a range of tympanoplasty graft materials and surgical techniques.

Otopathologic evaluation of temporalis fascia grafts following successful tympanoplasty in humans.

OBJECTIVE: Temporalis fascia is a commonly used graft material in tympanoplasty; however, little is known about how the histological structure of fascia remodels postimplantation. Herein, we aim to quantify the pre- and postoperative microstructure of temporalis fascia and compare histological findings to the native tympanic membrane (TM). METHODS: Temporal bone specimens having undergone successful subtotal or total drum replacement using temporalis fascia were identified (n = 3). Surgically prepared preimplantation temporalis fascia (PreTF, n = 4) and normal TMs (n = 5) were used as controls. Multiple measurements of thickness of PreTF and of normal and fascia reconstructed TMs at the mesotympanum and hypotympanum were obtained. Collagen fiber patterns of normal and reconstructed TMs were histologically described. RESULTS: In cases of fascia tympanoplasty, the mean time of surgery to death was 16 years (range 8-28 years). All cases contained an aerated middle ear without residual perforation. There was no significant difference between the thickness of PreTF and fascia of reconstructed TMs (234.9 ± 144.9 µm vs. 162.9 ± 71.9 µm, P = 0.1). The lamina propria and total thicknesses of controls (59.8 ± 39.3 µm and 83.7 ± 42.4 µm, respectively) were thinner than the PreTF and fascia-reconstructed TMs, respectively, in all cases (P ≤ 0.001, P ≤ 0.001). Reconstructed TMs contained a thick, longitudinal fiber structure that was qualitatively similar to PreTF. CONCLUSION: Based on human temporal bone specimens, temporalis fascia does not significantly remodel, change thickness, or change fibrous structure following successful tympanoplasty. Results have implications for selection and surgical preparation of graft materials in TM reconstruction. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:E351-E358, 2018.

Design, fabrication, and in vitro testing of novel three-dimensionally printed tympanic membrane grafts.

The tympanic membrane (TM) is an exquisite structure that captures and transmits sound from the environment to the ossicular chain of the middle ear. The creation of TM grafts by multi-material three-dimensional (3D) printing may overcome limitations of current graft materials, e.g. temporalis muscle fascia, used for surgical reconstruction of the TM. TM graft scaffolds with either 8 or 16 circumferential and radial filament arrangements were fabricated by 3D printing of polydimethylsiloxane (PDMS), flex-polyactic acid (PLA) and polycaprolactone (PCL) materials followed by uniform infilling with a fibrin-collagen composite hydrogel. Digital opto-electronic holography (DOEH) and laser Doppler vibrometry (LDV) were used to measure acoustic properties including surface motions and velocity of TM grafts in response to sound. Mechanical properties were determined using dynamic mechanical analysis (DMA). Results were compared to fresh cadaveric human TMs and cadaveric temporalis fascia. Similar to the human TM, TM grafts exhibit simple surface motion patterns at lower frequencies (400 Hz), with a limited number of displacement maxima. At higher frequencies (>1000 Hz), their displacement patterns are highly organized with multiple areas of maximal displacement separated by regions of minimal displacement. By contrast, temporalis fascia exhibited asymmetric and less regular holographic patterns. Velocity across frequency sweeps (0.2-10 kHz) measured by LDV demonstrated consistent results for 3D printed grafts, while velocity for human fascia varied greatly between specimens. TM composite grafts of different scaffold print materials and varied filament count (8 or 16) displayed minimal, but measurable differences in DOEH and LDV at tested frequencies. TM graft mechanical load increased with higher filament count and is resilient over time, which differs from temporalis fascia, which loses over 70% of its load bearing properties during mechanical testing. This study demonstrates the design, fabrication and preliminary in vitro acoustic and mechanical evaluation of 3D printed TM grafts. Data illustrate the feasibility of creating TM grafts with acoustic properties that reflect sound induced motion patterns of the human TM; furthermore, 3D printed grafts have mechanical properties that demonstrate increased resistance to deformation compared to temporalis fascia.