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Injectable Nanofibrous Microcarriers with Tunable PVA/Tannic Acid Ratios for Controlled miRNA Delivery in Intervertebral Disc Regeneration
Farzaneh Sabbagh, Paweł Nakielski
Institute of Fundamental Technological Research, Polish Academy of Sciences (IPPT PAN), Warsaw, Poland
Introduction: Degenerative disc disease (IDD) induces persistent back discomfort resulting from the degeneration of the nucleus pulposus (NP), and existing therapies, such as surgery, fail in restoring disc functionality [1]. Injectable biomaterials that administer therapeutic microRNAs (miRNAs) provide an effective method for nucleus pulposus regeneration[2]. This research formulates injectable nanofibrous microcarriers composed of polyvinyl alcohol (PVA), tannic acid (TA), and miRNA-encapsulated liposomes to enhance extracellular matrix (ECM) production and moderate inflammation, using biofabrication methods for minimally invasive intervertebral disc (IVD) repair.
Methods: Solutions (8% w/v) are formulated in five PVA:TA ratios (95:5, 90:10, 85:15, 80:20, 75:25) beside a pure PVA control (100:0) using distilled water. PVA (6.0–8.0 g) is solubilised at 80–90°C, prevailed by TA (0–2.0 g) at 40–50°C, 1% w/w sulfated alginate (S-ALG, 0.08 g) for extracellular matrix mimicking, and borax (0.1 g) for cross-linking purposes. The synthesis of cationic liposomes (DOTAP/cholesterol/mPEG-DSPE) encasing miR-145/miR-155 involves integrated electrospinning (0.5–1% w/v) and microfluidic mixing (flow rate ratio 3:1). Nanofibers (100–500 nm) are created by electrospinning (15–20 kV, 0.5–1 mL/h) and are cross-linked by the borate-diol linkages in borax. Microcarriers with 60–100 µm and 10–30 µm pores are produced by femtosecond laser micromachining and can then be injected using 30G needles [3].
Results: In all ratios, we expect homogenous nanofibers (100–500 nm), with increased TA content increasing fibre bioactivity. It is expected that microcarriers would have viscoelastic characteristics (Young's modulus ~0.1–1 MPa).With S-ALG facilitating electrostatic binding, liposomes (50–150 nm, zeta potential >10 mV) should attain >85% miRNA encapsulation efficiency and maintain release (80–90%) for 30 days. Pure PVA serves as a reference point for comparison, and the 80:20 ratio is thought to provide a compromise between mechanical stability and TA's anti-inflammatory properties.
Discussion: This polytherapeutic technology goes beyond hydrogel-based systems with transient drug release by combining electrospinning, liposome-mediated miRNA delivery, and laser micromachining. With S-ALG encouraging chondrogenic phenotypes and TA decreasing inflammation, tunable PVA:TA ratios enable bioactivity and mechanical optimization. Water stability is ensured via borax cross-linking, which is essential for NP's aquatic ecosystem. The injectable microcarriers meet the clinical requirements for IDD by enabling minimally invasive delivery.
References:
[1] H. Jiang, H. Qin, Q. Yang, L. Huang, X. Liang, C. Wang, A. Moro, S. Xu, Q. Wei, Effective delivery of miR-150-5p with nucleus pulposus cell-specific nanoparticles attenuates intervertebral disc degeneration, J. Nanobiotechnology. 22 (2024) 1–22.
[2] A. Jahani, M.S. Nourbakhsh, M.H. Ebrahimzadeh, M. Mohammadi, D. Yari, A. Moradi, Available 3D-printed Biomolecule-Loaded Alginate-Based Scaffolds for Cartilage Tissue Engineering Applications: A Review on Current Status and Future Prospective, Arch. Bone Jt. Surg. 12 (2024) 92–101.
[3] S. Zhang, Q. Shi, C. Christodoulatos, G. Korfiatis, X. Meng, Adsorptive filtration of lead by electrospun PVA/PAA nanofiber membranes in a fixed-bed column, Chem. Eng. J. 370 (2019) 1262–1273.
Keywords: miRNA delivery, PVA/tannic acid, IVD regeneration, nanofibrous, Biofabrication, microcarriers
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