The role of growth factors in peripheral nerve regeneration and opportunities for next-generation biological therapeutics

Biomaterials · 2026-04-08 · 1 citations

Raman spectroscopy with machine-learning classification for the prediction of stereotactic radiotherapy induced treatment toxicity in high-risk localised prostate cancer

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · 2026-01-29

Radiotherapy can lead to late-onset toxicity, to varying extents between individuals due to differences in radiosensitivity. Predicting which patients are most at risk is key to augmenting the therapeutic window. However, the underlying biological mechanisms remain poorly understood, and current experimental methods often lack clinical applicability. This study employs Raman spectroscopy to analyse biochemical profiles in peripheral lymphocytes and plasma, aiming to monitor radiotherapeutic response and predict intrinsic radiosensitivity in high-risk localised prostate cancer patients treated with stereotactic radiotherapy. Partial-least squares discriminant analysis classification of Raman spectra at baseline ( n = 20) from post-hormone therapy ( n = 19), mid-treatment (pre-4th fraction; n = 21) and 3-months after treatment ( n = 18) returned mean area under the curve values ranging from 0.88 to 0.93. Ensemble classifiers applied to imbalanced late toxicity datasets (grade 0–1, n = 16; grade 2+, n = 4) yielded mean F1 scores of 0.74 (random forest, lymphocytes) and 0.69 (AdaBoost, plasma); metrics based on best performing model for minority-class. Classical least squares lymphocyte and plasma toxicity models identified major concentration differences in amino acids, proteins, lipids, DNA and related biomolecules ( p < 0.05). These findings demonstrate the potential of Raman spectroscopy as a minimally invasive, objective tool for classifying blood-based biochemical profiles across radiotherapy treatment time points and distinguishing patients with late grade 0–1 and grade 2+ toxicity. • Therapeutic and intrinsic response of PCa patients to RT was investigated using RS. • RS in tandem with PLS-DA could discriminate baseline peripheral lymphocytes from subsequent treatment time points with high classification metrics. • RS of pre-treatment peripheral lymphocytes and plasma in tandem with ensemble classifiers (RF and AdaBoost) demonstrated the predictive potential of intrinsic biochemical profiles for the development of radiation-induced late toxicity.

Bio-inspired electronics: Soft, biohybrid, and “living” neural interfaces

Nature Communications · 2025-02-21 · 102 citations

Neural interface technologies are increasingly evolving towards bio-inspired approaches to enhance integration and long-term functionality. Recent strategies merge soft materials with tissue engineering to realize biologically-active and/or cell-containing living layers at the tissue-device interface that enable seamless biointegration and novel cell-mediated therapeutic opportunities. This review maps the field of bio-inspired electronics and discusses key recent developments in tissue-like and regenerative bioelectronics, from soft biomaterials and surface-functionalized bioactive coatings to cell-containing 'biohybrid' and 'all-living' interfaces. We define and contextualize key terminology in this emerging field and highlight how biological and living components can bridge the gap to clinical translation.

Controlled spatial and temporal release of neurotrophic growth factor from genetically modified tissue engineering living scaffolds

Journal of Tissue Engineering · 2025-11-01 · 1 citations

Peripheral nerve injuries (PNIs) affect thousands of patients yearly, often resulting in loss of function, sensation, and chronic pain. In critical-size defects, advanced surgical repair strategies often fail to restore full function. A key limitation is the lack of sustained, localized delivery of biological cues for axonal regeneration, such as growth factors. Glial-cell line-derived neurotrophic factor (GDNF) is known to promote axonal growth, Schwann cell migration, and neuronal survival, but uncontrolled release may cause axonal entrapment. We previously developed tissue-engineered nerve grafts (TENGs) composed of two neuronal populations connected by stretch-grown axons. In this study, we genetically modified the distal population to express human GDNF under a Tet-on inducible promoter, temporally controlling GDNF release through doxycycline administration. Modified TENGs survived implantation in a 1.5-cm rat sciatic nerve defect, supporting future studies. This approach offers a promising platform for spatially and temporally controlled neurotrophic factor delivery from tissue-engineered living scaffolds.

A Nonhuman Primate Model to Evaluate Treatments for Long‐Gap Ulnar Nerve Injury

Journal of Neuroscience Research · 2025-07-31

Among all upper extremity nerves, the ulnar nerve is both the most commonly injured and notoriously difficult to regenerate. Despite this, ulnar nerve injuries remain understudied. Nonhuman primates (NHPs) offer an ideal model for the human upper extremity, but existing NHP nerve trauma literature is biased towards median and radial injury models. To address this, a nonhuman primate ulnar nerve injury model was developed and regeneration assessed following sural nerve autografting using electrophysiological and histological techniques. Unilateral 4 cm ulnar nerve injuries were created at the mid-forearm level, sural nerve autografts were sutured into resulting defects (n = 3), and animals were survived for 6 months. At the terminal time point, intraoperative electrophysiological testing, tissue harvest, and tissue processing were performed. Naïve nerves (n = 5) served as controls. Animals appeared clinically normal throughout the study period, other than an expected decrease in fine hand muscle function. After 6 months, histological and electrophysiological evidence suggested that axons crossed the graft and reached distal muscle targets. However, regenerating nerves exhibited a reduced motor nerve conduction velocity, reduced compound action muscle potential (CMAP) amplitude and area under the curve, increased latency, and increased duration versus naïve controls as expected. Histological analysis revealed reduced axon diameters, thinner myelin sheaths, and smaller muscle fiber cross-sectional areas as compared to controls. At 6 months post-injury, 4 cm ulnar defects bridged with sural autografts show signs of ongoing regeneration and nascent reinnervation. Specific electrophysiological and histological benchmarks for ulnar nerve recovery following clinically relevant autografting are presented.

Author response for "A Nonhuman Primate Model to Evaluate Treatments for Long‐Gap Ulnar Nerve Injury"

2025-05-23

Astrocyte Transcriptomics in a Three-Dimensional Tissue-Engineered Rostral Migratory Stream

Cells · 2025-10-22 · 2 citations

The glial tube is a longitudinal structure predominantly composed of densely bundled, aligned astrocytes that projects from the subventricular zone (SVZ) to the olfactory bulb. Neural precursor cells (NPCs) generated in the SVZ migrate through this glial tube—referred to as the rostral migratory stream (RMS)—to replace olfactory bulb interneurons in the mammalian brain. RMS astrocytes have distinct morphological and functional characteristics. These characteristics facilitate the unique purpose of the RMS as an endogenous living scaffold directing NPC migration and maturation. However, the transcriptomic factors underlying these unique structure–function attributes versus standard stellate astrocytes have not been examined. We previously developed biofabrication techniques to create the first tissue-engineered rostral migratory stream (TE-RMS) that replicates key features of the glial tube in vivo. We have shown that TE-RMS astrocytes exhibit elongated nuclei, longitudinally aligned intermediate filaments, and enrichment of key functional proteins—cytoarchitectural and surface features characteristic of native RMS astrocytes. In the current study, we performed RNA-seq on TE-RMS astrocytes in comparison to planar astrocyte cultures to identify gene expression patterns that may underlie their profound morphological and functional differences. Remarkably, we found 4,008 differentially expressed genes in TE-RMS astrocytes, with 2076 downregulated (e.g., LOC690251 and ccn5) and 1932 upregulated (e.g., lrrc45 and cntn1) compared to planar astrocytes. Moreover, there were 256 downregulated and 91 upregulated genes with &gt;3-fold change. We also conducted analyses of gene sets related to cytoskeleton and nuclear structure, revealing the greatest enrichment of actin-related components. Overall, the TE-RMS offers a platform to study the interplay between transcriptomic and cytoarchitectural dynamics in a unique astrocyte population.

Hybrid Diffuse Optics for Monitoring Cerebral Physiology After Traumatic Brain Injury

2025-01-01

Diffuse optics provides a non-invasive approach for neuromonitoring after traumatic brain injury. Using a swine model, we demonstrate its utility in detecting cerebral physiological changes, including cerebral water content, blood flow and oxygen metabolism. Full-text article not available; see video presentation

Astrocyte Transcriptomics in a Three-Dimensional Tissue-Engineered Rostral Migratory Stream

bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-27

Abstract The glial tube is a longitudinal structure predominantly composed of densely bundled, aligned astrocytes that projects from subventricular zone (SVZ) to olfactory bulb. Neural precursor cells (NPCs) generated in the SVZ migrate through this glial tube – referred to as the rostral migratory stream (RMS) – to replace olfactory bulb interneurons in the mammalian brain. RMS astrocytes have distinct morphological and functional characteristics facilitating their unique purpose as an endogenous living scaffold directing NPC migration and maturation. However, the transcriptomic factors underlying these unique structure-function attributes versus standard stellate astrocytes have not been examined. We previously developed biofabrication techniques to create the first tissue-engineered rostral migratory stream (TE-RMS) that replicates key features of the glial tube in vivo . We have shown that TE-RMS astrocytes exhibit elongated nuclei, longitudinally aligned intermediate filaments, and enrichment of key functional proteins – cytoarchitectural and surface features characteristic of native RMS astrocytes. In the current study, we performed RNAseq on TE-RMS astrocytes in comparison to planar astrocyte cultures to identify gene expression patterns that may underlie their profound morphological and functional differences. Remarkably, we found 4008 differentially expressed genes in TE-RMS astrocytes, with 2076 downregulated (e.g. LOC690251, ccn5 ) and 1932 upregulated (e.g. lrrc45 , cntn1 ) compared to planar astrocytes. Moreover, there were 256 downregulated and 91 upregulated genes with &gt;3-fold change. We also conducted analyses of gene sets related to cytoskeleton and nuclear structure, revealing greatest enrichment of actin-related components. Overall, the TE-RMS offers a platform to study interplay between transcriptomic and cytoarchitectural dynamics in a unique astrocyte population.

Astrocyte Interactions With Ti ₃ C ₂ T <i> _x </i> MXene Flakes: Insights Into Viability, Morphology, and Functionality (Adv. Mater. Interfaces 20/2025)

Advanced Materials Interfaces · 2025-10-01

Ti3C2Tx MXene on Astrocytes This image shows Ti3C2Tx MXene flakes on the astrocyte membrane. Ti3C2Tx MXene is a two-dimensional nanomaterial with promising properties for application in bioelectronics. In this first systematic evaluation of astrocyte–MXene interactions, scanning electron microscopy reveals Ti3C2Tx adhering to astrocytes without causing any evident alteration of the membrane. Alongside viability, morphology, and calcium imaging assays, these findings establish for the first time the biocompatibility of Ti3C2Tx MXene with astrocytes. More details can be found in the Research Article by Flavia Vitale, D. Kacy Cullen, and co-workers (DOI: 10.1002/admi.202500261).