## 1 Introduction
Despite the appealing features of cellulose-based material and their mild immunogenicity in vivo [17], the non-degradability of such materials in the human body [18] make cellulose an unfavorable material for clinical application. The application of denuded amniotic membrane, which is composed of non-fibrillar meshwork containing collagen type III, was reported previously as cell support for the transferring cell layer [19]. In 2018, crosslinking of decellularized amniotic membrane with 0.5% genipin was reported to significantly enhance the biostability and resistance of the amniotic membrane when exposed to enzymatic degradation. It was also shown that the genipin-crosslinked amniotic membrane expresses better biocompatibility with nasal fibroblasts compared to the native one, making it a suitable scaffold for respiratory tissue engineering applications [20]. Another support material that has the potential to be used in respiratory tissue engineering is collagen type I, being the most abundant collagen in the human body. Collagen type I is the major component of the extracellular matrix in most of the tissues and organs, and it is known to support cellular properties in vivo [21]. In vitro studies showed that increasing the concentration of collagen type I promotes the stratification of respiratory epithelial cells (RECs) and affects the morphology of the cells [22]. The commercially available bovine collagen cross-linked with glycosaminoglycan (Integra(r)) already has the Food and Drug Administration (FDA) and EU approval and is currently used in clinical practice for skin treatment [23]. Collagen fibers also possess some unique structural properties important for tissue engineering. The physical and mechanical properties of bovine collagen type I were extensively studied elsewhere [24]. It was reported that genipin cross-linked bovine collagen exhibits significantly improved mechanical features (stiffness, shrinkage, and swelling properties) and it is suitable for tissue engineering application in vivo. Bovine collidge exhibits a higher Young's modulus/stiffness (-500 MPa) compared to human native trachea (16.92 MPa). Additionally, collagen has high water affinity, low antigenicity, very good cell compatibility, and the ability to promote tissue regeneration [25]. These factors combined make collagen one of the most ideal biopolymers available for tissue engineering applications. However, due to bovine collagen's fast degradation rate, it is a suitable material for tracheal tissue engineering application [26]. Despite many recent attempts at the tissue engineering of human respiratory epithelium [27; 28], no ideal treatment for respiratory epithelium repair has yet been developed. Proper epithelialization of tissue-engineered airway constructs, poor vascularization, and less-than-favorable mechanical properties are the current challenges. Complex and often non-reproducible differentiation procedures and difficulty in maintaining the mucciliated phenotype of the primary airway epithelial cells are the major complications persisting in the field [29]. Hence, in this study, we introduced a three-dimensional (3D) model of an in vitro respiratory epithelium (RE) construct comprising RECs and fibroblasts from human nasal turbinate, which were incorporated into a freeze-dried ovine collagen scaffold and grown in an air-liquid interface culture condition. The aim was to use the constructed respiratory epithelium for respiratory epithelium regeneration or substitution. To the best of our knowledge, this is the first time that this proposed approach is reported in the tissue engineering of the respiratory epithelium. The significance of the study is the application of FDA-approved collagen from bovine source, which makes the 3D respiratory epithelium construct a promising candidate for future clinical use.