Aligned tissue architecture is a basic proviso for several organs and tissues like intervertebral discs, tendons, ligaments, muscles, and neurons, which comprises type-I collagen as an eminent extracellular matrix (ECM) protein. Exploiting type-I collagen for the biofabrication of aligned constructs via different approaches is becoming apparent, as it comprises a major fraction of connective tissue, exhibits abundance in ECM, and displays poor antigenicity and immunogenicity, along-with the ease of remodelling adaptability. Collagen hydrogels or composite scaffolds with uniaxial fibril alignment or unidirectional pore architecture having different sizes and densities are being fabricated using electrical, mechanical, and freeze-drying processes which are applicable for tissue engineering and regenerative purposes. This review focuses on several multifarious approaches employed to fabricate anisotropic structures of type-I collagen which influences fibril alignment, pore architecture, stiffness anisotropy, and enhanced mechanical strength and mimics the tissue native microenvironment ushering cell niches to proliferate and differentiate into tissue specific lineages.

Deformity or fissure within the annulus fibrosus (AF) lamellar structure often results in disc herniation leading to the extrusion of nucleus pulposus (NP), which pushes the adjacent nerve, causing low back pain. Low back pain, frequently associated with the degeneration of the intervertebral disc (IVD), affects around 80% of the population worldwide. The difficulty in mimicking the unique structural characteristics of the native AF tissue presents several challenges to the tissue engineering field for the development of the long-term effective therapeutic strategy for AF tissue regeneration. The AF cell niche possesses less reparative capacity for regeneration and thus compels to develop a strategy to recapitulate damaged AF tissues. We have fabricated a polycaprolactone-supported electrocompacted type-I collagen patch (A-PCL-NH2+Col-I) using surface-modified electrospun-aligned polycaprolactone (A-PCL) nanofibers cross-linked with an electro-compacted type-I collagen patch (Col-I) using EDAC-NHS (1-ethyl-3-[3-(dimethylamino)­propyl] carbodiimide hydrochloride and N-hydroxy succinimide). This subtle approach offered a 3D biodegradable scaffold with dense aggregates of anisotropic collagen-I nanofibrils coupled with electrospun-aligned PCL nanofibers, which provide high tensile strength (4.21 ± 1.07 MPa), moduli (24.496 ± 4.85 MPa), low subsidence to failure, and high-water absorption ability. The systemic organization of both the polymers within the scaffold, evident from attenuated total reflectance–Fourier transform infrared (ATR-FTIR) spectroscopy, revealed a uniform degree of fiber alignment assessed by differential interference contrast (DIC) microscopy, field-emission scanning electron microscopy (FE-SEM), and cryo-SEM. The aminolysis of A-PCL nanofibers was established by energy-dispersive X-ray analysis (EDX), while circular dichroic spectra showed that the electro-compacted Col-I patch displayed a triple helical structure, characteristic of collagens. Moreover, the scaffold revealed more hydrophilic, rough nano-features, which provided ample ligands for cell attachment supporting adequate proliferation of primary goat annulus fibrosus (AF) cells, oriented along the fiber direction, and also favored sufficient production of collagen type-I (+32-fold change) and a glycosaminoglycan extracellular matrix (+2.3-fold change) as compared to cell control, respectively. This study thus demonstrates for the first time the practicability of creating an aligned polycaprolactone-supported electrocompacted type-I collagen hydrogel (A-PCL-NH2+Col-I) with significant biomechanical properties, which can be used as an alternative to repair and regenerate AF fissures in degenerated IVD.

Translation of tissue engineering strategies for the regeneration of intervertebral disc (IVD) requires a strong understanding of pathophysiology through the relevant animal model. There is no relevant animal model due to differences in disc anatomy, cellular composition, extracellular matrix components, disc physiology, and mechanical strength from humans. However, available animal models if used correctly could provide clinically relevant information for the translation into humans. In this review, we have investigated different types of strategies for the development of clinically relevant animal models to study biomaterials, cells, biomolecular or their combination in developing tissue engineering-based treatment strategies. Tissue engineering strategies that utilize various animal models for IVD regeneration are summarized and outcomes have been discussed. The understanding of animal models for the validation of regenerative approaches is employed to understand and treat the pathophysiology of degenerative disc disease (DDD) before proceeding for human trials. These animal models play an important role in building a therapeutic regime for IVD tissue regeneration, which can serve as a platform for clinical applications.