Objective To determine the in vivo biocompatibility of septal neocartilage constructs developed in vitro by an alginate intermediate step. Study Design Prospective, animal model. Setting Research laboratory. Subjects and Methods A murine model was used to examine the maturation of neocartilage constructs in vivo. Chondrocytes collected from patients undergoing septoplasty were expanded in monolayer and suspended in alginate beads for three-dimensional culture in media containing human serum and growth factors. After in vitro incubation for 5 weeks, the constructs were implanted in the dorsum of athymic mice for 30 and 60 days (n=9). After the mice were sacrificed, the constructs were recovered for assessment of their morphological, histochemical, biochemical, and biomechanical properties. Results The mice survived and tolerated the implants well. Infection and extrusion were not observed. Neocartilage constructs maintained their general shape and size, and demonstrated cell viability after implantation. The implanted constructs were firm and opaque, sharing closer semblance to native septal tissue relative to the gelatinous, translucent pre-implant constructs. Histochemical staining with hematoxylin and eosin (H&E) revealed that the constructs exhibited distinct morphologies characteristic of native tissue, which were not observed in pre-implant constructs. DNA and type II collagen increased with duration of implantation, whereas type I collagen and glycoaminoglycans (GAG) decreased. Mechanical testing of a 60-day implanted construct demonstrated characteristics similar to native human septal cartilage. Conclusions Neocartilage constructs are viable in an in vivo murine model. The histologic, biochemical, and biomechanical features of implanted constructs closely resemble native septal tissue when compared to pre-implant constructs.
The ability to engineer virtually limitless quantities of autologous cartilage could have a profound impact on facial plastic and reconstructive surgery. The strategies used to refine human cartilage culture techniques have successfully produced neocartilage constructs with biochemical and biomechanical properties approaching those of native septal tissue. With the steady progress achieved in recent years, there is great capacity for the proximate realization of surgically implantable tissue-engineered cartilage constructs.
Objectives/Hypothesis Tissue-engineered septal cartilage may provide a source of autologous cartilage for repair of nasal defects. Production of clinically useful neocartilage involves multiple steps that include manipulating the culture environment. Partial pressure of oxygen (ppO2) is a property that has been shown to influence cartilage development. Specifically, studies suggest low ppO2 augments in vitro growth of articular cartilage. Although in vivo measurements of articular cartilage ppO2 have demonstrated hypoxic conditions, measurements have not been performed in septal cartilage. The objective of this study was to determine the ppO2 of septal cartilage in vivo. Study Design Prospective, basic science. Methods The ppO2 was measured in 14 patients (mean ± standard deviation age, 35.9 ± 14.5 years; range, 18–63 years) during routine septoplasty or septorhinoplasty using the OxyLab pO2 monitor (Oxford Optronix Ltd., Oxford, UK). Measurements were taken from the septum and inferior turbinate. Each patient’s age and sex were recorded. Results The average ppO2 measured at the septum and inferior turbinate was 10.5 ± 10.1 mm Hg (1.4 ± 1.3%) and 27.6 ± 12.4 mm Hg (3.6 ± 1.6%), respectively. The ppO2 of these locations was significantly different (P < .005). Advancing age was positively correlated with septal ppO2 (R2 = 0.42; P < .05). Septal ppO2 showed no significant sex variation. Conclusions This is the first report of in vivo measurement of ppO2 in septal cartilage. The data demonstrate reduced oxygenation of septal cartilage relative to the inferior turbinate. This elucidates an important characteristic of the in vivo milieu that can be applied to septal cartilage tissue engineering.
Objective To determine and compare the bending moduli of native and engineered human septal cartilage. Study Design Prospective, basic science. Setting Research laboratory. Subjects and Methods Neocartilage constructs were fabricated from expanded human septal chondrocytes cultured in differentiation medium for 10 weeks. Constructs (n=10) and native septal cartilage (n=5) were tested in a 3-point bending apparatus, and the bending moduli were calculated using Euler–Bernoulli beam theory. Results All samples were tested successfully and returned to their initial shape after unloading. The bending modulus of engineered constructs (0.32 ± 0.25 MPa, mean ± SD) was 16% of that of native septal cartilage (1.97 ± 1.25 MPa). Conclusion Human septal constructs, fabricated from cultured human septal chondrocytes, are more compliant in bending than native human septal tissue. The bending modulus of engineered septal cartilage can be measured, and this modulus provides a useful measure of construct rigidity while undergoing maturation relative to native tissue.
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