Plant-derived architectures provide a unique reservoir of hierarchical, anisotropic, and transport-optimized design principles that can be systematically translated into functional biomaterials for regenerative implants. Unlike conventional scaffold engineering approaches that rely on artificially generated porosity and isotropic architectures, plant tissues exhibit evolutionarily optimized vascular networks, graded mechanical stiffness, and stimulus-responsive morphologies that directly address challenges in mass transport, stress distribution, and adaptive integration in biomedical implants. This review critically examines how plant structural hierarchies, from cellulose microfibril alignment to multichannel vascular bundles, are mechanistically mapped onto modern biofabrication platforms, including decellularization, extrusion-based 3D printing, direct ink writing, electrospinning, and 4D printing. Particular emphasis is placed on quantitative structure-property-function relationships, such as anisotropic modulus ratios (E||/E⊥), channel diameter-diffusion coupling, swelling-induced curvature programming, and surface energy-biofouling interactions, that govern biological outcomes including angiogenesis, osteogenesis, myogenic alignment, and anti-infective performance. Representative case studies demonstrate that plant-inspired multichannel scaffolds enhance vascular infiltration and bone regeneration in vivo, aligned cellulose-based systems enable programmable shape morphing for minimally invasive deployment, and biomimetic surface microtopographies reduce fouling without antibiotic reliance. However, critical translational challenges remain, including immunological validation of decellularized plant matrices, mechanical fatigue under cyclic physiological loading, lubricant stability in slippery interfaces, and scalability under Good Manufacturing Practice (GMP) conditions. By integrating plant biomechanics, materials science, and advanced biofabrication, plant-inspired biomaterials emerge as a promising, yet early-stage strategy for engineering adaptive, vascularized, and multifunctional implants. Future progress will depend on rigorous quantitative validation, long-term in vivo performance studies, and standardized manufacturing frameworks that bridge biomimetic design with clinical translation.
Piezoelectric materials have emerged as promising electroactive biomaterials in regenerative medicine owing to their ability to convert mechanical forces into electrical signals and vice versa. These materials reproduce aspects of the body's native bioelectric microenvironment and influence key cellular processes, including adhesion, proliferation, migration, and differentiation. Clinically, piezoelectricity has been exploited, in dental implants, where electromechanical activity enhances osseointegration and long-term stability. This review provides a comprehensive overview of the principles of piezoelectricity, the major classes of piezoelectric materials, and recent advances in fabrication strategies such as electrospinning, additive manufacturing, and nanogenerators. Applications across bone, nerve, cartilage, skin, and cardiovascular tissues are critically examined, with emphasis on mechanosensitive ion channels, intracellular signalling pathways, and gene regulation. Safety concerns, including ion release from ceramic materials, and the emergence of biocompatible, lead-free alternatives are discussed alongside translational barriers related to scalability, regulatory approval, and device integration. The aim of this review is to provide a mechanistic and clinically oriented perspective that informs the design of next-generation piezoelectric materials. Finally, future directions in self-powered implants and piezoelectric catalysis are highlighted to support their clinical translation for tissue repair and regenerative therapies. STATEMENT OF SIGNIFICANCE: This review uniquely integrates the fundamental and translational aspects of piezoelectric biomaterials in regenerative medicine. We highlight how piezoelectric cues regulate cell behaviour through electrical stimulation, ion channel activation, particularly Ca²⁺ flux and downstream signalling pathways such as Wnt/GSK3β and PI3K/Akt. By linking these mechanisms to gene expression profiles and functional outcomes across bone, nerve, cartilage, cardiovascular, and skin tissues, this work provides a tissue-specific perspective that has not been comprehensively addressed before. Importantly, we emphasise the multifunctionality of piezoelectric scaffolds, showcasing their immunomodulatory, angiogenic, and biomechanical benefits. The review further bridges insights across chemistry, biology, materials science, and biofabrication, offering constructive guidance for designing next-generation, clinically translatable piezoelectric biomaterials.
The heterogeneity of the tumor microenvironment poses a significant challenge to the success of anti-cancer therapeutics. Consequently, there is an urgent need to generate comprehensive data to elucidate the mechanisms underlying tumor resistance and to inform the rational and systematic application of anti-cancer drugs to mitigate drug resistance. In-vitro tumor models based on established cell lines are widely employed in studying the mechanisms of action of drugs; however, these traditional models often fail to accurately recapitulate the complexity of native tumors, particularly in terms of the heterogenous and intricate tumor microenvironment, including cellular composition, intercellular communication, and interactions between cells and extracellular matrix. As a result, preclinical data often diverges from clinical outcomes. In recent years, the emergence of patient-derived three-dimensional (3D) models including spheroids, organoids, tumor-on-a-chip systems, and 3D bioprinting has offered promising alternatives for addressing these limitations and enhancing the predictive power of tumor drug screening. In this review, we explore the relationship between the complexity of the tumor microenvironment, tumor drug resistance, and then introduce the current biofabrication techniques enabling the reconstruction of 3D tumor models in vitro. We delve deeper into a myriad of applications of such models for a wide range of cancer indications. These models offer a morfailures andlly relevant platform for evaluating anti-cancer drugs with the potential to improve translational accuracy, reduce drug development failures, and accelerate the discovery of cancer therapies.
Stem cell-based bone tissue engineering is often limited by insufficient osteogenic differentiation and inadequate vascularisation, largely attributable to the absence of a biomimetic stem cell niche. This study aimed to develop a human gingiva-derived decellularised extracellular matrix hydrogel (G-dECM) as a supportive microenvironment for three-dimensional (3D) coculture spheroids of STRO-1⁺ gingival mesenchymal stem cells (sGMSC) and human umbilical vein endothelial cells (HUVEC), thereby promoting the expression of osteogenic and angiogenic markers. Human gingival tissue was processed through decellularisation, enzymatic digestion, and sol-gel transformation to prepare G-dECM hydrogel. Composite 3D sGMSC/HUVEC spheroids (GHS) were generated and encapsulated within G-dECM. Morphological assessment, viability evaluation, and osteogenic differentiation analyses were conducted. Transcriptomic profiling was performed to identify G-dECM-associated regulatory signalling pathways. G-dECM exhibited a porous, collagen-rich structure enriched with bioactive ECM proteins. Encapsulation of GHS within G-dECM enhanced cellular viability, promoted the expression of osteogenic and angiogenic markers, and improved spheroid structural integrity compared with matrix-free controls. Transcriptomic analysis revealed activation of TGF-β/SMAD and BMP signalling pathways associated with osteogenic differentiation. G-dECM provides a biomimetic stem cell niche that supports the osteogenic and angiogenic phenotypes of 3D sGMSC/HUVEC spheroids, establishing an integrated regenerative graft system combining seed cells, scaffold, and endogenous signalling cues. This G-dECM-based composite graft strategy offers a promising translational approach for the regeneration of alveolar bone defects associated with periodontal disease, trauma, or tooth extraction.
Accurate and up-to-date anatomical information is critical for effective treatment planning in breast cancer adaptive radiotherapy. Cone-beam computed tomography facilitates real-time plan optimization but lacks sufficient electron density accuracy for direct clinical application. To address this limitation, we propose a novel unsupervised deep learning framework that integrates the Mamba architecture with an artifact disentanglement network to form the Artifact Disentanglement Network-Mamba model. This study proposes an unsupervised deep learning framework, ADN-Mamba, integrating an Artifact Disentanglement Network (ADN) with the structured state-space model Mamba for high-precision sCT synthesis from breath-hold CBCT (BH-CBCT). The model uses three encoders (CBCT content, CT content, artifact) and two generators to disentangle anatomical features from artifacts in CBCT. Mamba enhances the ability of the model to capture long-range dependencies, improving representation of complex anatomical structures. The Artifact Disentanglement Network-Mamba model achieved a mean absolute error of 54.97 HU within the body. The mean absolute percent errors of synthetic and real CT images in the soft tissue (-150 HU to 150 HU) and bone (200 HU to 1500 HU) regions were 46.26% and 30.98%, respectively. The gamma pass rate of the calculated dose on sCT compared with that on pCT is 97.74% under the 2%/2 mm criterion. The proposed model outperforms six other state-of-the-art methods in terms of image quality, dose accuracy, and radiomic feature consistency. By overcoming challenges such as registration errors and the absence of paired cone-beam computed tomography-computed tomography datasets, the proposed framework demonstrated superior performance in terms of anatomical fidelity and dose calculation accuracy. ADN-Mamba enables precise BH-CBCT-to-CT synthesis via unsupervised artifact disentanglement and Mamba's long-range modeling, demonstrating superior performance in image quality, dose calculation accuracy, and radiomic consistency. This framework provides a reliable tool for online dose calculation and target delineation in breast ART. Future work will focus on extending the model to 3D data and multicenter validation.
Extrachromosomal circular DNAs (eccDNAs) have been discovered in various species and play a significant role in cancer development. However, our understanding of their chromosomal biogenesis is limited. Here, we identified a correlation between eccDNA generation and the density of transcription regulatory elements, such as enhancers and promoters. We find that the regulators of enhancer-promoter interactions, including RAD21, LDB1 and YY1, may contribute to eccDNA production, with only a modest effect from transcriptional activity itself. The BRD4 inhibitor JQ1 reduces eccDNA production, while the HDAC inhibitor TSA induces an increase of eccDNAs. This TSA-induced effect can be rescued by the TSA antagonist, ITSA. The generation of eccDNA positively correlates with the density of R loops. Furthermore, large eccDNA breakpoints are found to be coordinated with TAD boundaries and inclined to align at enhancers and promoters. Our study suggests that eccDNAs are more frequently detected from regulatory regions in the genome, consistent with their generation being associated with enhancer-promoter dynamics.
Angiogenesis is a fundamental prerequisite for functional tissue regeneration, and biomaterials that drive endogenous vascularization hold immense translational potential for treating tissue defects, organ damage, and ischemic diseases. Herein, gelatin methacryloyl (GelMA) and chitosan methacryloyl (CSMA) were synthesized via a copolymerization-based modification method. Hydrogel microspheres were prepared by emulsification, followed by cross-linking through photoinitiator-induced radical polymerization under UV light. Combined with freeze-drying, size-tunable porous GelMA/CSMA composite microspheres (G/CMS) were fabricated. The as-prepared G/CMS establish a favorable pro-regenerative microenvironment by integrating size-dependent mechanical feedback and charge-mediated cellular interactions. Specifically, CSMA incorporation imparted a positive surface charge, enhancing cellular affinity, while smaller diameters amplified mechanical stimuli promoting adhesion via mechanotransduction. In vitro, the optimized formulation (G/CMS-B) significantly promoted the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs), and upregulated key angiogenic genes (VEGF, ANG, KDR) without exogenous growth factors. In vivo, subcutaneous implantation and hindlimb ischemia models confirmed accelerated neovascularization and blood flow recovery. The developed G/CMS exhibited excellent biocompatibility, controllable degradability, injectability, and excellent elastic recovery. This synergistic platform effectively modulates physicochemical cues to promote vascularization, offering a promising, cost-effective strategy for regenerative medicine.
Visualising and quantifying vascular 3D microstructure are essential for linking it to mechanics and disease. This study evaluated Phospho-Tungstic Acid (PTA) and 1:2 Hafnium-substituted Wells Dawson Polyoxometalate (1:2 Hf-POM) as Contrast-Enhancing Staining Agents (CESAs) for X-ray-based 3D Histology (X3DH) using Contrast-Enhanced Micro-focus Computed Tomography (CECT), as alternatives to classical 2D histology for visualising and quantifying collagen and elastin. Native and enzymatically digested porcine carotid artery segments, with varying elastin and collagen content, were CESA-stained and μCT-imaged to generate X3DH data, used to calculate Elastin-Stained Volume Fraction (E-SVF). Equivalent CESA-stained and unstained sections underwent Verhoeff's (VH), Picrosirius Red (PR), and Haematoxylin-Eosin (H&E) histology to measure Elastin-Stained Area Fraction (E-SAF), Collagen-SAF (C-SAF), and cell density. X3DH results were compared with histology to evaluate correspondence and staining effects. Both CESAs produced strong signal colocalisation with elastic lamellae and weaker staining in the remaining ECM. E-SVF for both CESAs correlated strongly with E-SAF, but E-SVF values were about two times lower than E-SAF (r2PTA=0.86, p<0.0001, slopePTA=0.42 | r21:2-Hf-POM=0.86, p<0.0001, slope1:2-Hf-POM=0.49). This highlights CECT as a non-destructive, accurate method for quantifying vascular microstructure with fewer artefacts than classical 2D histology. VH and PR staining were visually and quantitatively (±10% E-SAF and C-SAF equivalence) unaffected by CESA-staining. PTA-staining with cryopreservation caused loss of nucleic contrast, while 1:2 Hf-POM influenced ECM haematoxylin uptake, reducing nuclei visualisation and cell count accuracy in H&E histology. Both CESAs bind non-specifically but preferentially to elastin, enabling reliable quantification. However, vascular collagen remains difficult to visualise as ECM is non-specifically stained. STATEMENT OF SIGNIFICANCE: Understanding the three-dimensional microstructure of vascular tissues is crucial for revealing how it governs mechanics and disease progression. This study investigates two contrast agents, phospho-tungstic acid and 1:2 hafnium-substituted Wells-Dawson polyoxometalate, for their potential to visualise and quantify two of the key constituents within arterial tissue, collagen and elastin, using Contrast-Enhanced Micro-focus Computed Tomography (CECT). By assessing these agents combined with CECT as alternatives to gold-standard histological techniques for the visualisation and quantification of these key extracellular matrix components, this research advances CECT as a non-destructive alternative to traditional histological techniques. Improved three-dimensional imaging of vascular architecture deepens our understanding of arterial structure-function relationships and supports more accurate computational modelling, disease characterisation, and the development of next-generation cardiovascular devices.
Osteoarthritis is a chronic disabling disease characterized by progressive degeneration of articular cartilage. The condition is characterized by an imbalance in the inflammatory response, the degradation of the extracellular matrix, the apoptosis of chondrocytes, and the disorder of the immune microenvironment. The present clinical efficacy of the treatment is unsatisfactory due to the limited self-healing ability of the articular cartilage. In recent years, there has been a growing body of research focusing on the therapeutic potential of exosomes (Exos) derived from mesenchymal stem cells (MSCs). The findings of these studies have demonstrated the significant potential of MSC-derived exosomes as a promising cell-free therapeutic strategy. This article provides a synopsis of the research progress and mechanisms of mesenchymal stem cell-derived exosomes (MSC-Exos) from diverse tissue sources in the treatment of osteoarthritis. Furthermore, the application of MSC-Exos in the treatment of osteoarthritis were also discussed. The review will provide a valuable reference for future research directions in this field.
Lung cancer remains the leading cause of cancer-related mortality worldwide, with surgically inoperable cases posing a significant clinical challenge. Although microwave ablation (MWA) is a viable treatment option for non-surgical patients, its effectiveness is often compromised by substantial complications and inadequate prevention of tumor recurrence or progression. To address these limitations, we developed a multifunctional hydrogel system (aPD1@Cur-Mg/GH) that integrates antitumor immunomodulation with pleural sealing capabilities. This hydrogel combines a gelatin methacryloyl (GelMA)/o-nitrobenzyl alcohol-modified hyaluronate (HANB) matrix (GH) with an aPD1-loaded curcumin-embedded magnesium-polyphenol network (Cur-Mg/aPD1). By utilizing the photocrosslinking properties of GelMA and HANB, the aPD1@Cur-Mg/GH hydrogel forms a robust, adhesive, and compression-resistant structure that is ideal for pleural sealing and tissue repair. Upon degradation, the hydrogel releases Mg2 + ions and curcumin, which promote M1 macrophage polarization and enhance CD8+ T cell infiltration, thereby synergizing with MWA to improve the efficacy of immune checkpoint blockade therapy. Our findings demonstrate that this dual-functional hydrogel significantly modulates the post-ablation tumor immune microenvironment and presents a promising strategy for enhancing lung cancer immunotherapy following MWA.
Genetically engineered bacterial protein nanoparticles (GVs-E.coli) enhance the therapeutic efficacy of high-intensity focused ultrasound (HIFU) by virtue of their intrinsic tumor tropism, favorable biosafety profile, and inherent cavitation activity. However, the cavitation behavior of GVs-E.coli has not been systematically characterized, and the underlying regulatory mechanisms remain poorly elucidated presenting a critical knowledge gap that limits their optimal theranostic application. Herein, we investigated the cavitation behaviors of GVs-E.coli within a wall-free flow channel embedded in tissue-mimicking agarose phantoms using a customized ultrasound platform. Passive cavitation detection (PCD) was performed under varying peak negative pressures (PNPs) and bacterial concentrations, with acoustic emissions analyzed in both time and frequency domains. Our results revealed that the stable cavitation (SC) threshold of GVs-E.coli was 1.6 MPa and the inertial cavitation (IC) threshold was 2.2 MPa. Cavitation dose was positively correlated with PNP, yet harmonics and sub-harmonics exhibited distinct growth patterns.A critical concentration threshold of OD600 (optical density at 600 nm) = 1.0 was identified for robust cavitation activity. These findings lay the groundwork for optimizing GVs-E.coli-mediated ultrasound therapies and accelerate their clinical translation as next-generation sonosensitizers.
Autologous grafts remain the clinical gold standard for vascular reconstruction; however, their use is limited by donor site morbidity, poor availability, and long-term failure. Synthetic alternatives, while effective in large-caliber vessels, fail in small-diameter applications (<6 mm) due to thrombosis, intimal hyperplasia, and biomechanical mismatch. In this context, tissue-engineered vascular grafts (TEVGs) emerge as a solution, requiring biomaterials that closely replicate the structural, mechanical, and hemocompatible properties of native vessels. Aliphatic polyesters such as polylactic acid, polyglycolic acid, and poly(ε-caprolactone) are extensively studied but show poor endothelialization and mechanical deficiency. In contrast, poly(butylene trans-1,4-cyclohexanedicarboxylate) (PBCE) attracts interest for its biocompatibility, thermal stability, and processability. Its copolymerization with Pripol 1009, a commercial fatty diacid, enables modulation of mechanical properties and degradation rate, two of the key parameters for vascular engineering. In this work, electrospun scaffolds based on these copolymers are fabricated in flat and tubular formats and characterized in terms of morphology, mechanical behavior, hemocompatibility, and endothelialization potential. Certain formulations display mechanical properties comparable to native vessels, support endothelialization and smooth muscle cell adhesion, and do not trigger coagulation pathways in in vitro assays. These results identify PBCE/Pripol copolymers as promising candidates for next-generation TEVGs, bridging the gap between synthetic reliability and biological performance in small-diameter vascular applications.
The gut microbiota plays a pivotal role in bio-transforming dietary components, including tryptophan, an essential amino acid that undergoes microbial metabolism. Microbial metabolism of tryptophan yields indole-3-propionic acid (IPA), an emerging biomarker for gut inflammation. Current IPA detection relies on expensive, time-consuming mass spectrometry. To address this limitation, a fluorescent nanosensor system is presented that uniquely features two optical modalities: one utilizing near-infrared (NIR) emission of a central single-walled carbon nanotube (SWNT), and a separate, visible emission from the corona phase polymer, a cationic conjugated polyelectrolyte (CP3). Selective IPA molecular recognition occurs at the latter, but the binding is optically reported via quenching in both the visible and NIR emission channels. The two modalities provide complementary advantages: CP3-SWNTs' NIR channel enables detection in strongly scattering tissue environments due to reduced Rayleigh scattering at longer wavelengths. Conversely, CP3 visible channel facilitates future rapid, cost-effective point-of-care biological sample screening. Functionality of both modalities is maintained within a gelatin metacrylate hydrogel offering potential for future continuous in vivo monitoring of IPA dynamics. The sensor reveals significant differences in plasma IPA levels between healthy controls and patients with active gut inflammation: ulcerative colitis and Crohn's disease, highlighting its promise in rapid gut health assessment.
The heart is viscoelastic and exhibits both viscous and elastic behavior with deformation. Cardiac viscoelasticity influences heart function by regulating the volume of blood that can fill, and subsequently be pumped from, the cardiac chambers. Tissue viscoelasticity can also influence cellular functions, motivating the need to measure and model viscoelasticity from the cellular to the organ scale under healthy and disease conditions. Here, we review current protocols, instrumentation, and results from cardiac viscoelastic measurements from the organ to the subcellular level. Since viscoelasticity is regulated by tissue structure and composition, we describe what is known about the viscoelasticity of intracellular and extracellular proteins, cardiac cells, and cardiac tissue, as well as how changes in these proteins with disease progression may influence cardiac viscoelasticity. Finally, we discuss the outlook for the field, including recommendations for standardizing reports of cardiac viscoelastic measurements to increase their utility for biomaterials design for tissue engineering, cardiovascular modeling, and diagnosis.
Peripheral nerve injury (PNI), a common clinical condition, heavily relies on the functional condition of Schwann cells (SCs) for effective repair. Emerging evidence shows that excessive pyroptosis of SCs hinders neural regeneration. Low-intensity pulsed ultrasound (LIPUS), a non-invasive physical therapy, shows potential in tissue repair; however, its role in regulating SCs pyroptosis remains unclear. This study explores the mechanism by which LIPUS improves PNI recovery by reducing SCs pyroptosis. We find that LIPUS significantly enhances motor function recovery, promotes axonal regeneration and remyelination, and decreases gastrocnemius muscle atrophy through a rat sciatic nerve crush model. LIPUS biomechanically mitigates mitochondrial dysfunction in SCs, thereby suppressing the NLRP3/Caspase-1/GSDMD-N pyroptosis signaling pathway. This inhibition reduces IL-1β and IL-18 release, boosting SCs proliferation, migration, and clearance of myelin debris, collectively fostering a regenerative microenvironment that supports axonal regrowth, remyelination, and functional recovery. Our results demonstrate a mechanobiological mechanism by which LIPUS promotes peripheral nerve regeneration through alleviating pyroptosis, providing a promising therapeutic approach for PNI.
Photodynamic therapy (PDT) is promising but limited by its dependence on specialized photosources, clinic-based administration, and prolonged post-treatment light avoidance due to phototoxicity side effects. Here, we report mild-sunlight-activated PDT (SunPDT) microneedle patches incorporating polymeric photosensitizers with an intrinsic "on-off" reactive oxygen species (ROS)-generating mechanism, enabling bio-safe, deep-tissue, and self-administered PDT without fixed clinic visits and strictly prolonged light avoidance post-treatment. Rationally designed photosensitizers generate robust ROS under low-intensity mild sunlight (12 mW cm-2) excitation, and feature an intrinsic "on-off" ROS generation mechanism that confines ROS generation to lesions, even when photosensitizers diffuse into surrounding healthy tissues. Microneedle-enabled deep photosensitizer delivery and excitation by the near-infrared component of sunlight together allow self-administered treatment of deep-seated lesions without scheduled clinic visits. Importantly, the SunPDT patch's triple-safety design, low-intensity mild sunlight excitation, local delivery of photosensitizer by microneedles, and an intrinsic "on-off" ROS generation mechanism, eliminate post-treatment prolonged light avoidance, ensuring bio-safe PDT. Using female psoriatic mice as a proof-of-concept model, our "on-off" SunPDT microneedle patches achieve high therapeutic efficacy and patient-friendly, self-administered treatment, and outperform clinical Protoporphyrin IX patches, which demonstrate weaker effects and require prolonged light shielding. Therefore, this study establishes a promising design for a lifestyle-integrated PDT platform.
Xenopus laevis survives seasonal droughts by entering a hypometabolic state known as aestivation. One of the mechanisms employed by X. laevis to mitigate aestivation-induced tissue atrophy is gene regulation of pro-survival proteins. We further expand on the role of anti-apoptotic signaling in X. laevis by investigating the effect of signal transducer and activator of transcription (STAT) signaling on downstream anti-apoptotic genes in control and dehydrated liver and skeletal muscle of X. laevis. Herein, we found that STAT signaling is differentially regulated between tissues. STAT3 signaling in the liver and STAT5 signaling in skeletal muscle lead to the selective upregulation of downstream anti-apoptotic proteins. Additionally, pro-apoptotic STAT1 signaling is found to be attenuated in both tissues during dehydration stress. Overall, our results indicate an important role for anti-apoptotic proteins during dehydration stress and their contribution in mitigating aestivation-induced atrophy.
This review explores the role of in vitro electrical and mechanical stimulation in modulating wound-healing behavior, with a primary focus on the predominant skin cell types: fibroblasts and keratinocytes. By analyzing the existing literature, we delineate the complex relationships between stimulation parameters-such as voltage, current, frequency, and mechanical strain-and cellular responses, including proliferation and migration. Our data-driven approach compiled more than 390 experimental data points for electrical stimulation and over 170 for mechanical stimulation in vitro, constructing a comprehensive library of cell responses that were previously fragmented and difficult to compare across studies. We critically evaluate various stimulation platforms and configurations, emphasizing their influence on cellular mechanobiology and their translational potential in regenerative medicine. Ultimately, this review underscores the necessity of a multi-parameter optimization strategy to effectively exploit electromechanical cues for targeted skin tissue regeneration.
Viscoelastic hydrogels crosslinked by dynamic bonds hold great promise for mimicking the matrix dynamics of native tissues in cell culture and tissue engineering. Yet, their application in light-based bioprinting remains largely unexplored due to the incompatibility between reversible bond formation and photocrosslinking. This study addresses this key challenge by presenting a new class of photocrosslinkable, hydrazone-based bioinks developed from two modified polymers (Gel-A-DAAM and Gel-C-DAAM). These polymers are designed to enable reversible bond formation within hydrogel networks by attaching polymerizable groups to the polymer backbone via modular hydrazone conjugation chemistry. The resulting materials exhibit distinct mechanical properties depending on their hydrazide substituent, swelling medium, incubation temperature, and incubation time. Storage moduli of produced hydrogels vary between 0.08 - 1.2 kPa, which spans multiple scales of physiologically relevant tissue environments. The novel bioinks are suitable for droplet-based bioprinting followed by light-based crosslinking, and support cell spreading of human fibroblasts. Notably, the morphology of encapsulated cells varies with different hydrazide substituents, highlighting the potential of the developed bioink system to systematically investigate cell-matrix interactions. The combination of biological tunability and printability positions this system as a promising platform for fabricating next-generation tissue-mimetic constructs using advanced bioprinting technologies.
Epicardial radiofrequency ablation can fail when lesions are not sufficiently deep or transmural, yet intraoperative feedback remains largely indirect. This study presents a fiber-based, side-viewing near-infrared spectroscopy (NIRS) probe with multiple source-detector separations (SDS) to enable depth-sensitive mapping of lesions on the porcine left-ventricular epicardium. Monte Carlo simulations predicted progressively deeper sampling with increasing SDS, motivating the use of multi-separation acquisition for depth-resolved contrast. Experiments were performed on 11 porcine hearts with 133 irrigated epicardial lesions spanning a wide depth range, with lesion depth ground truth reconstructed from post-stain gross section measurements. SDS-dependent spectral signatures were observed across lesions with depths greater than 4 mm, lesions with depths ≤ 4 mm, adipose tissue, and untreated epicardial muscle, and optical indices capturing these patterns were identified for lesion and adipose classification, as well as for lesion-depth sensitivity. Lesion and adipose indices achieved strong receiver operating characteristic (ROC) performance across SDS (lesion AUC 0.87-0.91; adipose AUC 0.94-0.97), and depth-sensitive indices exhibited monotonic trends with lesion depth (R² up to 0.97). Applying a random forest lesion mask enabled depth-sensitive maps that were consistent with variations in the ground truth.