Innovation for diabetic peripheral neuropathy: a focus on emerging bioengineering solutions
Aims: To review diabetic peripheral neuropathy (DPN) pathophysiology and emerging bioengineering approaches aimed at moving treatment beyond pain relief towards disease modification.
Methods: This narrative review covered DPN mechanisms, treatments, experimental models, biomaterial-based drug delivery, microfluidic platforms and DPN assessment and monitoring.
Results: DPN is multifactorial, involving hyperglycaemia, dyslipidaemia, advanced glycation, impaired insulin signalling, oxidative stress and microvascular dysfunction. Oxidised LDL activates NADPH oxidase through LOX-1, TLR4 and RAGE. Experimentally, palmitate damaged Schwann cells and neuronal mitochondria, while free fatty acids promoted cytokine release, PKC activation and endothelial apoptosis; oxysterols may also promote neuroinflammation. Treatment remains focused on neuropathic pain, including pregabalin, duloxetine, ion-channel inhibitors, anti-inflammatory and antioxidant agents, pirenzepine, stem cells and VM202 gene therapy; most clinical studies assessed pain rather than nerve structure or function. Biomaterial-based drug delivery was a major focus. Nanoparticles, hydrogels, microneedles and nerve conduits were developed to improve tissue targeting, provide sustained or stimulus-responsive release, preserve active agents and reduce systemic toxicity. Curcumin-loaded nanoparticles reduced neuroinflammation and P2X3 signalling. VEGF-grafted gold nanoparticles promoted angiogenesis and sciatic nerve regeneration in diabetic rats, while resveratrol-loaded tetrahedral framework nucleic acids restored sensory function and promoted neurovascular regeneration in diabetic mice. Thermosensitive hydrogels delivered bFGF, NGF or angiotensin II, while segmented microneedles combined sustained vitamin B9 delivery with glucose-responsive insulin release. These approaches remain preclinical and rely mainly on chemically induced rodent models. Microfluidic platforms separated dorsal-root-ganglion cell bodies from axons and allowed co-culture with Schwann cells or keratinocytes. The studies implicated several microRNAs in impaired axonal growth under hyperglycaemic conditions. Future DPN-on-a-chip systems should incorporate hyperlipidaemia, vascular and immune components and support drug screening. The review covered assessment tools including corneal confocal microscopy (CCM), artificial intelligence and wearable sensors. CCM-based AI models achieved AUCs of up to 0.95 but require external prospective validation in larger cohorts.
Conclusions: Biomaterial delivery and microfluidic modelling may advance treatment and mechanistic research, but nerve regeneration in DPN remains clinically unproven, requiring representative models and validated structural and functional endpoints.
Comments. The unusual choice of a review for Publication News was motivated by its major strength: the distinctive integration of DPN pathophysiology and clinical management with emerging biomaterials, microfluidic disease models, artificial intelligence and wearable technologies. It provides a comprehensive account of metabolic mechanisms, including hyperglycaemia, dyslipidaemia and impaired insulin signalling, while critically examining targeted drug delivery, DPN-on-a-chip platforms and advanced monitoring methods. This broad translational perspective is particularly valuable for identifying potential routes towards disease-modifying treatment.
The limitations largely reflect the narrative design of the review. Evidence from clinical trials, animal studies and prototype technologies is discussed despite differing levels of maturity, without a systematic search or formal quality assessment. The lipid section also focuses predominantly on type 2 diabetes, with limited consideration of triglyceride-rich lipoproteins, ApoB particle burden, lipid-lowering therapy or dyslipidaemia in type 1 diabetes. These limitations do not undermine the review’s scientific value or forward-looking perspective.
Maryam Ferdousi
Reference. He Z, Diao J, Hamel FG, Duan B. Innovative strategies for diabetic peripheral neuropathy: From clinical management to emerging bioengineering solutions. Bioact Mater. 2026 Feb 17;61:312-338. doi: 10.1016/j.bioactmat.2026.02.023. PMID: 41737633; PMCID: PMC12926992.
