Regenerating Nucleus Pulposus of the Intervertebral Disc Using Biodegradable Nanofibrous Polymer Scaffolds

Abstract

Low back pain is a leading health problem in the United States, which is most often resulted from nucleus pulposus (NP) degeneration. To date, the replacement of degenerated NP relies entirely on mechanical devices. However, a biological NP replacement implant is more desirable. Here, we report the regeneration of NP tissue using a biodegradable nanofibrous (NF) scaffold. Rabbit NP cells were seeded on the NF scaffolds to regenerate NP-like tissue both in vitro and in a subcutaneous implantation model. The NP cells on the NF scaffolds proliferated faster than those on control solid-walled (SW) scaffolds in vitro. Significantly more extracellular matrix (ECM) production (glycosaminoglycan and type II collagen) was found on the NF scaffolds than on the control SW scaffolds. The constructs were then implanted in the caudal spine of athymic rats for up to 12 weeks. The tissue-engineered NP could survive, produce functional ECM, remain in place, and maintain the disc height, which is similar to the native NP tissue.

Injectable nanofibrous spongy microspheres for NR4A1 plasmid DNA transfection to reverse fibrotic degeneration and support disc regeneration

“…These HP-pDNA polyplexes loaded PLGA NS were combined with NF-SMS (Fig 2 B-H). The interconnectivity between pores is important for cell migration and mass transfer and the NF morphology is advantageous for NP regeneration [55, 56]. The release profile of pDNA polyplexes was examined (Supplementary Fig.…”

“…Using a large 3D nanofibrous scaffold, we previously regenerated NP tissue and implanted it into the caudal spine [55, 56]. The implanted tissue was found to remain in place, contain functional ECM, and maintain the disc height.…”

“…The nano-scale and micro-scale structures of NF-SMS may advantageously support tissue regeneration [64-66]. On the nanometer scale, a nanofibrous architecture mimicking the structure of extracellular matrix (ECM) can promote tissue regeneration [56, 67]. A porous structure on the micrometer scale likely increases gene delivery vehicle-loading efficiency, decreases the amount of degradation product, facilitates cell-cell and cell-matrix interactions, and provides easy path for nutrient and metabolic waste transfer [68-71].…”

Gene therapy for nucleus pulposus regeneration by heme oxygenase-1 plasmid DNA carried by mixed polyplex micelles with thermo-responsive heterogeneous coronas

“…We previously implanted tissue-engineered NP fabricated with 3D nanofibrous scaffolds into the caudal spine [41,42]. It remained in place, produced functional ECM, and maintained the disc.…”

Nanostructured Injectable Cell Microcarriers for Tissue Regeneration

“…On the one hand, scaffolds with a nanoarchitecture resembling the natural ECM nanostructure can enhance cell-matrix interactions and tissue regeneration [9,46]. For example, by mimicking the architecture of natural collagen fibrils, NF scaffolds enhanced multiple types of tissue formation, including bone [46], dentin [70], intervertebral disks [71], cartilage [9,72] and blood vessels [39]. In another example, inorganic/organic nanocomposites which mimic mineralized tissue ECM composition at the nanoscale have been used to create cell carriers for hard tissue regeneration [72][73][74][75][76][77].…”