Enhancing Muscle Recovery: Drug Release from Smart Nanofiber Membranes in Atrophy

Abstract

Muscle atrophy, a common complication resulting from prolonged joint immobilization, postoperative limb fixation, or nerve injury, significantly impairs patients' quality of life. Conventional oral medications and physical rehabilitation exhibit limited efficacy due to poor bioavailability, insufficient targeting, and systemic side effects. Recent advances in nanofiber-based therapies offer innovative solutions by combining localized drug delivery, electrical stimulation, and neuro-muscular repair mechanisms.

Tan et al. presented the development of an implantable, epigallocatechin gallate (EGCG)-loaded core–shell nanofiber membrane (EPLA NFM) for preventing immobilization-induced muscle atrophy. Fabricated via coaxial electrospinning using polylactide/gelatin, the EPLA NFM ensured sustained EGCG release, overcoming limitations of oral administration, such as oxidation and low bioavailability. In vivo experiments demonstrated that EPLA NFM increased muscle wet weight by 30% and cross-sectional area by 25% in murine models, while suppressing key atrophy markers (MuRF1, MAFbx) and enhancing gait function. Mechanistically, EPLA NFM inhibited TNF-α/NF-κB inflammatory pathways, scavenged reactive oxygen species (ROS), and activated the Akt signaling pathway to promote myogenesis. Additionally, the membrane exhibited broad-spectrum antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), reducing postoperative infection risks. RNA-seq analysis revealed EPLA NFM's role in downregulating pro-inflammatory genes and upregulating myogenic pathways. The biodegradable, biocompatible nanofiber system offered a promising localized therapeutic strategy for muscle atrophy, combining anti-inflammatory, antioxidative, and pro-regenerative effects without systemic side effects. This innovation highlighted the potential of nanofiber-based drug delivery in musculoskeletal rehabilitation.

Another study introduced a self-powered gelatin/polycaprolactone nanofiber membrane (PCLG-D NFM) for preventing denervation-induced muscle atrophy, which typically reduced muscle fiber size by 40–50% within two weeks. The PCLG-D NFM, dip-coated with aspirin/lysine-loaded polypyrrole (PPy) nanoparticles, leveraged piezoelectric properties to convert mechanical energy from natural movements into electrical stimulation (5 V output), triggering on-demand drug release. In mice models, this approach increased muscle weight by 44%, improved gait function, and reduced atrophy markers (MuRF1, MAFbx) by suppressing inflammation and oxidative stress. Transcriptomic analysis revealed that the NFM inhibited the renin-angiotensin system (RAS), mitigating vascular remodeling and inflammation. Exercise further enhanced therapeutic outcomes, boosting electromyographic signals and nerve regeneration. The NFM’s biodegradability, biocompatibility, and localized drug delivery circumvented systemic side effects associated with oral non-steroidal anti-inflammatory drugs (NSAIDs). These findings highlight the potential of self-powered nanofibers as a targeted, motion-responsive therapy for muscle atrophy, offering a promising alternative to conventional treatments.

Further advancing this technology, a self-powered PCLG-D nerve conduit was engineered to simultaneously repair peripheral nerve damage and prevent muscle atrophy. The experimental results showed that the PCLG-D nerve conduit had good biocompatibility, mechanical strength and degradability, and could generate self-powered output (up to 5V) through mechanical stimulation and achieve controlled release of drugs. In the mouse sciatic nerve injury model, the PCLG-D nerve conduit significantly promoted nerve regeneration, reduced muscle atrophy, and inhibited cell apoptosis by activating the insulin signaling pathway to inhibit neuronal apoptosis and preserved muscle mass, demonstrating synergistic "nerve-muscle" crosstalk. Transcriptome analysis further revealed the molecular mechanism by which the nerve conduit promoted nerve repair by upregulating the expression of genes such as IRS1 and SOX2. In addition, exercise training could enhance the electrical output of the nerve conduit, further improving its therapeutic effect. This study provided an innovative self-powered material strategy for the treatment of peripheral nerve injury, which had the dual functions of nerve repair and muscle protection.

These nanofiber-based strategies provide distinct yet complementary therapeutic avenues: EPLA NFM targets immobilization-induced atrophy via antioxidative/anti-inflammatory drug delivery; PCLG-D NFM integrates self-powered electrostimulation with pharmacotherapy for denervation atrophy; and the PCLG-D nerve conduit combines nerve repair with muscle protection. Their evolution reflects a progression from passive drug release (EPLA) to active bioelectronic modulation (PCLG-D NFM) and ultimately to multifunctional neuro-muscular regeneration (PCLG-D conduit).

Key advantages include localized drug delivery (minimizing systemic toxicity), biodegradability (eliminating secondary removal surgeries), and multifunctionality (anti-inflammatory, pro-regenerative, and electroactive properties). Future directions may involve integrating EGCG’s antioxidative effects with self-powered conduits to optimize combinatorial therapies. As these technologies advance toward clinical translation, long-term efficacy and safety evaluations will be critical to establishing their role in regenerative medicine.

Date of Award	12 Feb 2026
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Bee Luan KHOO (Supervisor), Jinlian HU (Supervisor), Hiu Wai Raymond LAM (Co-supervisor) & Mingliang HE (Co-supervisor)