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. Author manuscript; available in PMC: 2021 May 28.
Published in final edited form as: Ann Otol Rhinol Laryngol. 2020 Sep 25;130(4):395–404. doi: 10.1177/0003489420959692

Table 1.

Summary Table Detailing Each Study, by Anatomic Site of Application.

Study Design Seeded Cells/Growth Factors
Study (Year) Size (n) In vivo In vitro Nanofiber Material Results
Tracheal Reconstruction
Dharmadhikari et al5 50 Yes, mice Yes PET:PU 20:80 percent weight BM-MNCs

  1. Synthetic scaffolds support re-epithelialization in orthotopic patch implantation.

  2. Limited epithelial coverage of the segmental synthetic scaffolds both with and without BM-MNCs
Wu et al6 55 Yes, rabbits Yes PGS/PCL with pedicled fascia N/A

  1. Fast-degrading PGS/PCL led to quick in vivo remodeling, allowing the formation of pedicled fascia tracheal grafts with adequate mechanical strength.
Pepper et al7 8 Yes, sheep No PET:PU 20:80 percent weight BM-MNCs

  1. All animals had signs of graft stenosis and lack of epithelialization at the graft site.

  2. Half of animals demonstrated infectious processes of the lung parenchyma.
Romanova et al8 N/A No Yes Chitosan-gelatin-PLLA Airway epithelial cells, tracheal/dermal fibroblasts, MSCs

  1. A bi-layered non-woven scaffold was created, and optimal parameters for cell proliferation and differentiation were determined.

  2. Basal airway epithelial cells differentiated appropriately along the surface of the scaffold.
Wiet et al9 4 Yes, mice No PET:PU 20:80 percent weight BM-MNCs

  1. Grafts were able to recapitulate findings of stenosis and delayed epithelialization in previous studies.
Dharmadhikari et al10 25 Yes, mice Yes PET:PU and resorbable PLCLPGA N/A

  1. Synthetic scaffolds were supraphysiologic in compression tests compared to native trachea.

  2. Non-resorbable scaffolds showed more stenosis, while resorbable scaffolds showed more collapse.
Best et al11 N/A No Yes PET and PU in ratios of either 8:2 or 2:8 percent weight BM-MNCs

  1. Grafts composed of 2:8 PET:PU with solid C-rings approximate the biomechanics of native ovine trachea.

  2. 2:8 PET:PU demonstrated superior cell seeding capacity of the two prototypes tested.
Townsend et al12 5 Yes, sheep No PCL nanofibers layered with PCL C-rings N/A

  1. Mechanically robust, suturable, air-tight, bioresorbable graft for use in tracheal reconstruction.

  2. Poor tissue integration.
Pepper et al13 7 Yes, sheep No PET:PU 20:80 percent weight BM-MNCs

  1. Bronchoscopy was required less frequently in the group that was stented versus dilated (P = .05).

  2. 100% of dilations and 29% of stent placements required urgent follow up bronchoscopy (P = .05).
Wu et al14 27 Yes, rats Yes PLCL/collagen Rat tracheal epithelial cells and chondrocytes

  1. PLCL/collagen scaffolds had good biocompatibility, showing epithelial and chondrocyte proliferation.

  2. Pre-vascularized bi-layered PLCL/collagen grafts showed capillary regeneration, reduced immunogenicity and tracheal tissue regeneration.
Ghorbani et al15 6 Yes, rabbits Yes PCL, collagen coated PCL, PCL blended with collagen Chondrocytes, adipose-derived MSCs

  1. A cylindrical hybrid construct of PCL blended with collagen and decellularized aorta showed favorable shape, mechanical properties, biocompatibility and cell adhesion.
Clark et al16 5 Yes, sheep Yes PET:PU 70:30percent weight BM-MNCs

  1. Seeded TETG explants demonstrated wound healing, epithelial migration, and delayed stenosis when compared to their unseeded counterparts.
Mahoney et al17 N/A No Yes PCL/chitosan Porcine TBE cells

  1. PCL and chitosan were prepared in different ratios, and nanofibers of 90:10 PCL/chitosan ratio demonstrated good cellular attachment.

  2. All showed low toxicity and adequate tensile strength.
Bridge et al4 N/A No Yes PET (8%, 30% and 10%) Epithelial, fibroblast and smooth muscle cells

  1. Provides a relevant platform to allow the culture of fully differentiated adult cells within 3D, tissue-specific environments.
Jang et al1 14 Yes, guinea pigs Yes PCL/collagen hUCS

  1. PCL/hUCS-NF scaffold promoted cartilage and epithelial regeneration over artificial trachea without inflammation.
Hinderer et al18 N/A No Yes PCL/gelatin/dec-orin hPAECs

  1. Decorin can be electrospun while maintaining its functionality.

  2. The resulting 3D scaffold demonstrated low immunogenicity for hPAEC expansion in an in vitro analysis.
Tympanic Membrane Repair
Seonwoo et al19 108 Yes, rats Yes 8% PCL EGF

  1. Regeneration rates and time, plus size-reduction ability were highest in the aligned fibers with EGF (AF-wEGF) group versus random fibers with EGF and controls.
Li et al20 N/A No Yes Gelatin/genipin Skin fibroblasts, hUVEC

  1. Water-tolerance and good mechanical properties suitable for TM repair.
Mota et al21 N/A No Yes PLGA and PEOT/PBT Human MSCs

  1. Highest viability, cell density and protein content were detected in dual and triple scale scaffolds.

  2. These biomimetic micro-patterned substrates enabled cell disposal along architectural directions, appearing to be promising substrates for functional TM replacements.
Cranial nerve regeneration
Hackelberg et al22 2 Yes, guinea pigs Yes 4:1 blend of PLLA and PCL NPCs

  1. No evidence of inflammatory response

  2. Both subjects implanted with NPC-seeded and cell-free control scaffolds showed partial recovery of electrically evoked auditory brainstem thresholds, [auditory nerve]
Jang et al23 16 Yes, rats Yes PCL/collagen hUCS

  1. PCL/collagen/hUCS fibrous conduit provides more

  2. favorable micro-environmental conditions for facial nerve regeneration compared to PCL or PCL/collagen alone.
Hu et al24 30 Yes, rats No Silk fibroin N/A

  1. No overt inflammatory response.

  2. After 3 months, demonstrated that silk fibroin nanofiber grafts could promote facial nerve regeneration with effects comparable to those bridged with nerve autografts.
Osteogenesis
Jang et al25 40 Yes, guinea pigs Yes PCL/β-TCP/collagen versus PCL/β-TCP N/A

  1. PCL/β-TCP/collagen scaffold provided much broader cell attachment sites for osteogenesis after mastoid obliteration.

  2. Increased osteogenesis in PCL/β-TCP/collagen group.
Chondrogenesis
Dahl et al26 N/A No Yes PLGA hUCMSCs

  1. Compared to controls, hUCMSCs grown on PLGA nanofiber scaffolds had a higher differentiation index and increased auricular collagen mRNA expression.
San Marina et al27 N/A No Yes PLCL, PDO, PHBV-PCL, PH BY, PS AD-MSC

  1. PLCL scaffolds fragmented during processing and were unavailable for staining.

  2. PDO, PHBV-PCL, and PHBV showed the greatest relative amount of matrix deposition on incubation with the nasal chondrogenic supplement.

  3. Cells grown on the PS scaffold did not show evidence of matrix deposition.

Abbreviations: AD-MSC, Adipose-derived mesenchymal stem cells; BM-MNCs, Bone marrow-derived mononuclear cells; EGF, epidermal growth factor; hPAECs, human primary airway epithelial cells; hUCS, Human umbilical cord serum; hUVEC, Human umbilical vein endothelial cells; MSC, Mesenchymal stem cells; NPC, Neural precursor cells; PBT, Poly(butylene terephthalate); PCL, Polycaprolactone; PDO, Polydioxanone; PET, Polyethylene terephthalate; PEOT, Poly(ethylene oxide terephthalate); PGA, Polyglycolic acid; PGS, poly glycerol sebacate; PHBV, Poly(3-hydroxybutyrate-co-3-hydroxyvalerate); PLCL, Poly(L-lactide-co-caprolactone); PLGA, Poly(lactic-co-glycolic) acid; PLLA, poly(L-lactic) acid; PS, Polystyrene; PU, Polyurethane; TBE, tracheobronchial epithelial; β-TCP, Beta tri-calcium phosphate.