- ICH GCP
- Rejestr badań klinicznych w USA
- Badanie kliniczne NCT07717138
Study of the Biomechanical and Histological Properties of Septal, Auricular, and Costal Cartilage in the Context of Optimizing Total Nasal Reconstruction (Biom-CARTHIS)
Przegląd badań
Status
Szczegółowy opis
Current state of knowledge on the biomechanical properties of human nasal cartilage - implications for tissue engineering and reconstructive surgery
- Introduction and clinical context Nasal defects, whether of traumatic, tumoral, dermatological, or congenital origin, constitute a major disfigurement with significant physical and psychosocial repercussions. Nasal reconstruction traditionally relies on autologous grafts - septal, auricular, or costal cartilage - but this approach is limited by donor site morbidity, tissue availability, and the risk of graft failure. Existing alloplastic materials (silicone, Gore-Tex, Medpor high-density polyethylene) exhibit high rates of extrusion and infection, primarily due to mechanical incompatibility with the native tissue. The development of tissue-engineered substitutes thus constitutes a response to an unmet clinical need, provided that precise biomechanical data on the tissues to be replaced are available.
Structure and Histology of Cartilages Used in Nasal Reconstruction 2.1 Nasal Cartilage
The nose is composed of three main cartilages:
The septal cartilage: the central supporting structure of the entire nasal pyramid, directly adjacent to the nasal bones posteriorly. It includes the quadrangular cartilage anteriorly and the vomer elements posteriorly.
The alar cartilages (medial and lateral): mobile structures ensuring the patency of the nasal openings and maintaining the tip of the nose. The superior lateral cartilages: constituting the middle third of the nasal pyramid, and contributing to the stability of the dorsum.
Histologically, all nasal cartilages are of the hyaline type:
chondrocytes regularly distributed in an extracellular matrix (ECM) rich in type II collagen, glycosaminoglycans (GAGs), and proteoglycans, without elastic fibers. Septal cartilage has a higher cell density and a higher content of GAGs and proteoglycans than the alar and lateral cartilages, which contributes to its mechanical superiority.
2.2 Auricular Cartilage Auricular cartilage is an elastic cartilage, structurally distinct from the nasal cartilage. Its extracellular matrix is rich in elastic fibers distributed throughout the tissue, as confirmed by EVG staining positive in all regions of the auricle. This elastic nature gives it elastic recovery properties and dynamic behavior fundamentally different from those of nasal hyaline cartilage. 2.3 Costal cartilage Costal cartilage is of the hyaline type, sharing with septal cartilage an organization around a type II collagen network. It differs from it however by a denser architecture, a different matrix content, and a tendency to progressive warping after surgery, a manifestation of a mechanical creep behavior not captured by simple elastic modulus measurements.
Available Biomechanical Data on Human Nasal Cartilage 3.1 Studies on Living Surgical Tissue Studies conducted the first mechanical study on living septal tissue (45 specimens from reconstructive surgery, patients aged 15 to 60 years). Under confined compression, they measured a balance modulus and hydraulic permeability, and demonstrated that the balance modulus decreases significantly with age (p < 0.01), in parallel with a reduction in GAG content. However, this study has two major limitations in light of current needs: it is limited to septal cartilage only, without specifying the anatomical region of sampling (anterior or posterior), and does not include auricular or costal cartilage. Therefore, no comparison between the different donor sites used in nasal reconstruction is possible.
Studies analyzed the tensile properties of the human septum in 55 specimens from 28 surgical patients. They confirmed the tensile isotropy of the septum (no significant difference according to axis, age, or sex), with a stability modulus of 3.01 ± 0.39 MPa and a dynamic modulus of 4.99 ± 0.49 MPa. Again, the study was limited to the septum alone, without regional mapping or comparison with other donor sites.
Studies complement this analysis in confined compression of the living septum and reveal compressive anisotropy: the aggregate modulus is significantly higher in the vertical (0.70 ± 0.12 MPa) and caudal-cranial (0.66 ± 0.01 MPa) orientations than in the medial orientation (0.44 ± 0.04 MPa, p = 0.05). This compressive anisotropy, contrasting with tensile isotropy, reflects the organization of collagen fibers. The study remains however limited to the septum alone and does not provide information on other cartilages used in reconstruction.
A study was the first to mechanically test the inferior and superior lateral alar cartilages in humans in an intraoperative setting (5 patients undergoing septorhinoplasty). The tensile modulus of elasticity showed considerable variability: inferior alar cartilages 1.82-15.28 MPa, superior lateral cartilages 5.43-28.63 MPa, and septum 4.82-32.76 MPa. The very small sample size (n = 5) and the lack of formal statistical analysis are the main limitations of this pioneering work, which did not include auricular or costal cartilage.
3.2 Studies on cadaveric tissue
A study about nasal cartilage perform the most complete biomechanical mapping of human nasal cartilages to date, on 15 fresh-frozen male cadavers (mean age 56 ± 15 years), covering 26 anatomical points by indentation (Mach-1, indenter 0.2 mm, 300 g at 1 mm/s, relaxation 15 min). The Young's moduli in compression are as follows:
Cartilage | Young's Modulus (MPa) Posterior septal 3.47 ± 0.26 Medial septal 2.74 ± 0.37 Anterior septal 2.50 ± 0.32 Lateral alar 2.12 ± 0.50 Medial alar 2.06 ± 0.50 Superior lateral 0.98 ± 0.29 The posterior septum is significantly stiffer than the anterior septum (p < 0.01), a gradient explained by its proximity to the nasal bones. The alar cartilages, although less stiff in raw modulus, are structurally stiffer than the septal cartilages when corrected for thickness (p < 0.05), due to their arched architecture. This study does not, however, include auricular or costal cartilage. Another study about auricular cartilage performed the same mapping on the auricle (15 cadavers, 14 anatomical points). The compressive moduli are: concha 2.08 ± 0.70 MPa, antitragus 1.79 ± 0.56 MPa, antihelix 1.71 ± 0.63 MPa, tragus 1.67 ± 0.61 MPa, helix 1.41 ± 0.67 MPa. The concha exhibits the highest modulus (p < 0.01 vs. helix). Histological analysis confirms the homogeneous elastic nature of the entire auricle. This study does not include nasal or costal cartilage, and no direct comparison between donor sites is made.
A study made a methodological advance by modeling the nonlinear and strain-rate-dependent behavior of the three human nasal cartilages (cadaveric tissue, unconfined compression up to 32% strain). They demonstrate that linear models used in previous studies underestimate the actual physiological strain properties and provide hyperelastic and biphasic constitutive parameters for scaffold design. No auricular or costal cartilage is included. A most recent study on cadaveric tissue, simultaneously characterize the septum, superior lateral cartilage (ULC), and inferior lateral cartilage (LLC) in tension, compression, and ECM composition (collagen I, II, III, GAG, pyridinoline). The septum is the most hyaline (collagen II dominant), with a superior aggregate modulus and fracture resistance.
This study does not include auricular or costal cartilage.
What is missing from the literature Analysis of all available data reveals a central and unresolved gap: no study to date has compared, using fresh, hydrated living tissue and an identical standardized mechanical protocol, the biomechanical properties of the different cartilages actually used together in nasal reconstructive surgery-namely, the septal cartilage (distinguishing its anterior/quadrangular and posterior/vomerine anatomical regions), the auricular conchal cartilage, and the costal cartilage.
More specifically:
Studies using living tissue are each limited to a single type of cartilage, without inter-site comparisons and without precise regional mapping of the septum. Cadaveric studies provide detailed anatomical maps, but on non-living, frozen tissue, which can alter the intrinsic mechanical properties, and never compare the three donor sites in the same study with the same protocol.
No study has mechanically characterized the costal cartilage in relation to the nasal and auricular cartilages from the perspective of comparative nasal reconstruction.
- Implications for Substitute Materials The mean Young's modulus of human nasal cartilage under compression is around 2.72 ± 0.63 MPa for the septum, 2.09 ± 0.81 MPa for the alar cartilages, and 0.98 ± 0.29 MPa for the lateral cartilage. For comparison, Medpor has a modulus of approximately 150-300 MPa, a difference of two orders of magnitude. This mechanical mismatch generates micromovements at the implant-skin interface, contributing to extrusion. These data constitute the benchmark against which synthetic substitutes and tissue-engineered constructs should be developed and evaluated.
Typ studiów
Zapisy (Szacowany)
Kontakty i lokalizacje
Kontakt w sprawie studiów
- Nazwa: Mathilde WLODARCZYK
- Numer telefonu: 0033130754650
- E-mail: mathilde.wlodarczyk@ght-novo.fr
Lokalizacje studiów
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Île-de-France Region
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Pontoise, Île-de-France Region, Francja, 95300
- Hopital NOVO
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Kontakt:
- Khaled AL TABAA
- Numer telefonu: 0033130754040
- E-mail: khaled.altabaa@ght-novo.fr
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Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
- Dorosły
- Starszy dorosły
Akceptuje zdrowych ochotników
Metoda próbkowania
Badana populacja
Adult patients who have undergone septoplasty, rhinoseptoplasty, or otoplasty, and in whom excess cartilage was removed during the surgical procedure.
This cartilage, usually destined for disposal as surgical waste, is collected with the patient's consent, in accordance with current ethical and regulatory guidelines.
Opis
Inclusion Criteria:
- Adult patients who have undergone septoplasty, rhinoseptoplasty, or otoplasty, and in whom excess cartilage was removed during the surgical procedure.
This cartilage, usually destined for disposal as surgical waste, is collected with the patient's consent, in accordance with current ethical and regulatory guidelines.
Exclusion Criteria:
- Patient refusal
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
Kohorty i interwencje
Grupa / Kohorta |
Interwencja / Leczenie |
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Patients
Analysis of the biomechanical properties of septal cartilage as well as the cartilages used in nasal reconstruction and their histological identification.
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Analysis of the biomechanical properties of septal cartilage as well as the cartilages used in nasal reconstruction and their histological identification.
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Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Structural Histological Features of Septal, Costal, and Auricular Cartilage
Ramy czasowe: Through study completion, an average of one year
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Structural analysis of cartilage architecture (e.g., chondrocyte distribution/density, extracellular matrix organization, perichondrium integrity) performed ex vivo on surgical waste tissue samples by histological staining, compared across the three cartilage types.
No measurement is performed on participants in vivo.
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Through study completion, an average of one year
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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
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Young's Modulus of Septal, Costal, and Auricular Cartilage
Ramy czasowe: Through study completion, an average of one year
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Young's modulus (MPa) measured ex vivo on cartilage tissue discarded as surgical waste, to generate a biomechanical stiffness mapping by cartilage type.
No measurement is performed on participants in vivo.
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Through study completion, an average of one year
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Young's Modulus of Cartilage by Type, Patient Age, and Sex
Ramy czasowe: Through study completion, an average of 1 year
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Comparison of Young's modulus (MPa) values, measured ex vivo on discarded cartilage samples, stratified by cartilage type, patient age, and sex, to establish biomechanical reference data for future biomaterial development.
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Through study completion, an average of 1 year
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Współpracownicy i badacze
Sponsor
Śledczy
- Główny śledczy: Khaled AL TABAA, Hopital NOVO
- Główny śledczy: Emmanuel PAUTHE, CY Paris Université
Publikacje i pomocne linki
Publikacje ogólne
- Griffin MF, Premakumar Y, Seifalian AM, Szarko M, Butler PE. Biomechanical characterisation of the human nasal cartilages; implications for tissue engineering. J Mater Sci Mater Med. 2016 Jan;27(1):11. doi: 10.1007/s10856-015-5619-8. Epub 2015 Dec 16.
- Griffin MF, Premakumar Y, Seifalian AM, Szarko M, Butler PE. Biomechanical Characterisation of the Human Auricular Cartilages; Implications for Tissue Engineering. Ann Biomed Eng. 2016 Dec;44(12):3460-3467. doi: 10.1007/s10439-016-1688-1. Epub 2016 Jul 14.
- Gunter JP, Clark CP, Friedman RM. Internal stabilization of autogenous rib cartilage grafts in rhinoplasty: a barrier to cartilage warping. Plast Reconstr Surg. 1997 Jul;100(1):161-9. doi: 10.1097/00006534-199707000-00026.
- Rotter N, Tobias G, Lebl M, Roy AK, Hansen MC, Vacanti CA, Bonassar LJ. Age-related changes in the composition and mechanical properties of human nasal cartilage. Arch Biochem Biophys. 2002 Jul 1;403(1):132-40. doi: 10.1016/S0003-9861(02)00263-1.
- Richmon JD, Sage AB, Wong VW, Chen AC, Pan C, Sah RL, Watson D. Tensile biomechanical properties of human nasal septal cartilage. Am J Rhinol. 2005 Nov-Dec;19(6):617-22.
- Richmon JD, Sage A, Wong WV, Chen AC, Sah RL, Watson D. Compressive biomechanical properties of human nasal septal cartilage. Am J Rhinol. 2006 Sep-Oct;20(5):496-501. doi: 10.2500/ajr.2006.20.2932.
- Westreich RW, Courtland HW, Nasser P, Jepsen K, Lawson W. Defining nasal cartilage elasticity: biomechanical testing of the tripod theory based on a cantilevered model. Arch Facial Plast Surg. 2007 Jul-Aug;9(4):264-70. doi: 10.1001/archfaci.9.4.264.
- Chang B, Reighard C, Flanagan C, Hollister S, Zopf D. Evaluation of human nasal cartilage nonlinear and rate dependent mechanical properties. J Biomech. 2020 Feb 13;100:109549. doi: 10.1016/j.jbiomech.2019.109549. Epub 2019 Nov 29.
- Brown WE, Lavernia L, Bielajew BJ, Hu JC, Athanasiou KA. Human nasal cartilage: Functional properties and structure-function relationships for the development of tissue engineering design criteria. Acta Biomater. 2023 Sep 15;168:113-124. doi: 10.1016/j.actbio.2023.07.011. Epub 2023 Jul 16.
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Szacowany)
Zakończenie podstawowe (Szacowany)
Ukończenie studiów (Szacowany)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Inne numery identyfikacyjne badania
- CHRD 0126
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
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