A Polycaprolactone (PCL)-Supported Electrocompacted Aligned Collagen Type-I Patch for Annulus Fibrosus Repair and Regeneration

Abstract

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.

Angle‐ply scaffold supports annulus fibrosus matrix expression and remodeling by mesenchymal stromal and annulus fibrosus cells

“…Their acellular scaffolds demonstrated tensile modulus values similar to native AF and supported AF cell viability and an increase in metabolic activity over 7 days 47 . Dewle et al created PCL reinforced collagen fiber scaffolds that demonstrated uniaxial tensile properties similar to that of native AF and supported caprine AF cell viability, proliferation, adhesion, alignment along the fibers, and an increase in collagen type I mRNA expression 68 . While several other multilaminate scaffolds have been developed and characterized, 31 the AFRP described herein represents a simple approaches to creating a biomimetic, collagen‐based, multilaminate angle‐ply scaffold that has both mechanical and biological properties conducive to supporting annular repair.…”

Spheroid-Based Tissue Engineering Strategies for Regeneration of the Intervertebral Disc

“…Strategies to mechanically repair AF were developed (sutures, patches) but none of these techniques significantly altered annular healing in animal models nor demonstrated long-term benefits in clinical trials [ 175 ]. It is crucial that AF implants maintain adhesion to target tissue, especially under strain.…”

“…It is crucial that AF implants maintain adhesion to target tissue, especially under strain. Novel AF sealants have been generated and showed promising results [ 175 , 176 , 177 , 178 ]. Compared to acellular therapies, cell-based implants improve ECM deposition and organization in animal studies and show more successful AF remodeling in the long-term [ 178 ].…”

Alleviating the toxicity concerns of antibacterial cinnamon‐polycaprolactone biomaterials for healthcare‐related biomedical applications

“…PCL is a frequently used polymer in biomaterials, tissue engineering, and controlled delivery applications owing to its biocompatibility and biodegradability 39 . PCL is a semi‐crystalline polymer with a low degradation rate and good mechanical properties allowing it to have a high degree of flexibility and tensile strength, making it suitable for use in healthcare applications 40,41 . PCL is a hydrophobic polymer, which is advantageous for the preparation of hydrophobic active ingredients in common organic solvent systems.…”

“… 39 PCL is a semi‐crystalline polymer with a low degradation rate and good mechanical properties allowing it to have a high degree of flexibility and tensile strength, making it suitable for use in healthcare applications. 40 , 41 PCL is a hydrophobic polymer, which is advantageous for the preparation of hydrophobic active ingredients in common organic solvent systems. Additionally, it has great compatibility with volatile solvents simplifying the production process.…”