Small cell lung cancer is one of the most aggressive malignancies, characterized by rapid tumor growth, early metastatic spread and extremely poor survival. Although most patients initially respond to platinum-based chemotherapy, relapse is almost inevitable and treatment options at recurrence remain limited. The recent introduction of immune checkpoint inhibitors has provided only modest clinical benefit, largely due to the fact that these tumors are immunologically cold. These limitations highlight the urgent need to better understand the molecular features of small cell lung cancer in order to identify more effective therapeutic strategies. In this review, we summarize current knowledge of the molecular landscape of small cell lung cancer, with particular emphasis on transcriptome-based classifications that have identified four major molecular subtypes defined by distinct transcriptional regulators and gene expression programs. We discuss how these classifications have improved the biological understanding of the disease and stimulated efforts to develop subtype-specific therapeutic strategies. At the same time, we highlight important limitations of this framework, including the remarkable transcriptional plasticity of tumor cells, which allows dynamic transitions between subtypes and may contribute to therapeutic resistance. To address these challenges, we examine additional molecular features that may represent more stable vulnerabilities, including recurrent genomic alterations, such as the widespread loss of tumor suppressor genes or oncogene amplifications through extrachromosomal DNA. We also discuss emerging approaches aimed at identifying novel context-specific cancer dependencies, including genome-scale functional screens in vitro and in vivo and genetic restraint analyses. Finally, we consider the growing potential of liquid biopsy strategies, which exploit the high level of circulating tumor DNA in patients with this disease to detect clinically relevant genomic alterations and monitor tumor evolution. Overall, this review highlights both the opportunities and challenges associated with molecular stratification in small cell lung cancer. The integration of transcriptional classifications with genomic and functional approaches may help identify more robust therapeutic vulnerabilities and guide the development of more effective treatments for this highly aggressive disease.
Peripheral nerve defect repair remains a clinical challenge. Nerve guidance conduits (NGCs) are potential alternatives to autografts, but their performance can be compromised by the oxidative and inflammatory microenvironment after injury. Here, we fabricated MnO₂-loaded hydrogel NGCs at concentrations of 10, 50, and 100 μg/mL and evaluated them in a rat model of a 10-mm sciatic nerve defect. Among the three concentrations, the MnO₂@NMgel-10 (10 μg/mL) group yielded a higher sciatic functional index, denser and more orderly regenerated nerve tissue, and less gastrocnemius muscle atrophy than the hydrogel-only and higher-dose conduit groups. Early tissue analysis showed that the MnO₂@NMgel-10 group exhibited increased infiltration of CD68⁺CD206⁺ cells, upregulated expression of IL-10, and significantly downregulated expression of IL-1β, TNF-α, and 4-HNE. Furthermore, the MnO₂@NMgel-10 group showed satisfactory biosafety and biocompatibility. These findings reveal a non-monotonic concentration response and preliminarily confirm the feasibility of low-dose MnO₂-functionalized hydrogel NGCs for repairing peripheral nerve defects, providing new insights into the application of MnO₂ as a supplementary material for NGC fabrication.
Liver fibrosis is a hallmark pathological feature of chronic liver diseases and poses a major threat to the health of millions of people worldwide. Without timely diagnosis and effective intervention, liver fibrosis can progress to cirrhosis, liver failure, and even hepatocellular carcinoma (HCC). The limited availability of donor organs for orthotopic liver transplantation has driven the continuous search for alternative therapeutic strategies. However, conventional approaches, including pharmacotherapy, RNA-based therapies, and cell therapy, are often limited by insufficient therapeutic efficacy, poor targeting, and significant adverse effects, underscoring the urgent need for more effective treatment strategies. In recent years, biomaterials have emerged as promising platforms for liver fibrosis therapy owing to their excellent biocompatibility and tunable physicochemical properties. This review summarizes the recent advances in biomaterial-based therapeutic strategies for liver fibrosis, with a particular focus on nanomaterials, hydrogels, and microsphere-based delivery systems. The advantages and limitations of these biomaterial platforms are systematically discussed. Furthermore, we highlight the dual role of biomaterials not only as delivery vehicles for antifibrotic drugs, nucleic acids, and therapeutic cells but also as active platforms that modulate the fibrotic microenvironment and promote liver regeneration. Finally, the current status and future perspectives of biomaterial-based approaches in liver tissue engineering are discussed.
Traumatic spinal cord injury (SCI) is characterized by excessive reactive oxygen species (ROS) accumulation coupled with a sustained acidic lesion microenvironment, both of which severely hinder endogenous neural tissue repair. This study reports the fabrication and comprehensive in vitro and in vivo validation of a thermosensitive injectable hydrogel embedded with ROS-eliminating nanoparticles (DHA-PLL-TPL nanoparticles hydrogel,DT NP-Hydrogel) for localized SCI treatment. In hydrogen peroxide-challenged primary spinal cord neuron cultures and weight-drop contusion rat SCI models, locally injected DT NP-Hydrogel significantly reduced oxidative stress marker 4-hydroxynonenal (4HNE), pro-apoptotic Caspase-3(Casp3) expression, and gap junction protein connexin 43 (Cx43) levels, while simultaneously upregulating the neuron-specific marker class III β-tubulin (Tuj1). Collectively, our in vitro and in vivo data demonstrate that DT NP-Hydrogel mitigates secondary spinal cord damage and delivers potent neuroprotective activity, establishing it as a promising therapeutic strategy for SCI.
Airway barrier dysfunction is a hallmark of chronic lung diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease, and is often shaped by polymicrobial rather than single-species interactions with the host tissue. However, extended host-microbe co-culture with rapid-colonizing airway pathogens such as Pseudomonas aeruginosa is difficult to sustain in accessible in vitro systems, limiting mechanistic study of polymicrobial barrier and inflammatory dynamics. Here we developed and validated an aqueous two-phase system (ATPS) that spatially confines bacterial communities over a human bronchial epithelial-endothelial transwell co-culture, extending the stable co-culture window to 24 h while preserving assayable barrier and cytokine readouts. Using a validation-by-recapitulation approach, the platform reproduced established in vivo phenomena: P. aeruginosa-driven barrier disruption, attenuation of pathogenic effects by the commensals R. mucilaginosa and L. casei with preserved junctional architecture, and S. pneumoniae exacerbation of barrier permeability accompanied by elevated IL-8 despite apparent junctional preservation. This accessible ATPS-based biomaterials platform requires no microfluidic or iPSC-derived components and provides a tractable foundation for mechanistic studies of polymicrobial interactions at the airway epithelial barrier.
OBJECTIVE:Degenerative disc disease remains a primary cause of chronic back pain, yet current surgical treatments are often limited by the mechanical mismatch between implants and native intervertebral disc (IVD) tissue. This study investigates additively manufactured functionally graded Gyroid structures based on thermoplastic polyurethane (TPU) as biomimetic IVD replacements, focusing on the influence of geometry and material gradients on mechanical performance.
Methods: Gyroid-based constructs were fabricated by multi-material fused filament fabrication using TPU filaments of different stiffness. Their mechanical performance was evaluated under static and dynamic compressive loading. Finite element analysis was performed to investigate stress distribution within the Gyroid architecture, while micro-computed tomography (µCT) was used to assess manufacturing-related defects and structural integrity before and after 700,000 loading cycles.
Results: All investigated structures exhibited stable and reproducible mechanical behavior. However, only a single geometric configuration reached the targeted physiological load range of 4000-8000 N, irrespective of the material combination. The incorporation of an additional compliant TPU phase did not significantly alter the global force-deformation response compared with two-material configurations, indicating that structural geometry predominantly governs the compressive mechanical behavior. Dynamic testing demonstrated consistent damping capacities of approximately 20% across all configurations together with stable stiffness, storage modulus, and loss modulus during fatigue loading. Finite element analysis revealed homogeneous load distribution with localized stress concentrations at the curved Gyroid junctions. Quantitative µCT analysis showed no measurable increase in micro-porosity, void fraction, or interfacial defects after 600,000 loading cycles.
Conclusion: The findings demonstrate that the mechanical performance of TPU-based Gyroid IVD constructs is primarily governed by architectural design rather than material gradients under compressive loading. The combined experimental, numerical, and µCT analyses confirm the mechanical robustness and structural stability of the proposed functionally graded Gyroid structures, highlighting architecture-driven design as a promising strategy for mechanically compatible intervertebral disc replacements.
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CRISPR-based designer nucleases can facilitate genome engineering targeting almost any genomic locus. However, safe and efficient methods for delivering gene editors into primary human cells and tissues remain a central challenge. In this study, we employed a PepFect14 (PF14) analog, PF14-K, to deliver high-fidelity Cas9-ribonucleoproteins and non-viral repair templates into primary human skin cells to mediate gene editing and repair targeting genes underlying the group of genetic skin blistering disorders epidermolysis bullosa (EB). Peptide-RNP nanoparticles enabled consistent gene editing of >70% in primary wild type fibroblasts and >50% in primary wild type keratinocytes. In more difficult-to-transfect primary EB skin cells, this strategy facilitated up to 68% exon deletion-mediated reframing targeting COL7A1 and 37% precise homology-directed repair of a prevalent LAMB3 mutation. Compared to electroporation, the gold standard for ex vivo delivery, PF14-K enabled similar total yields of edited cells. Deliverable PF14-K nanoparticles are highly cost-effective, as they can be formed on the benchtop through a simple mix-and-incubate approach, with future potential to deliver base and prime editors.
Therapeutic challenges in endometrial carcinoma (EC) arise from the limited efficacy and toxicity of current treatments. Although exosome-based RNA interference shows promise, its clinical translation is hindered by inefficient cargo loading, low yields, and poor tumor targeting. We have engineered an exosome platform (cRGD-ExoM) that integrates the following innovations: Firstly, RNA motifs enable the enrichment of shRNA loading by over 80-fold for targeting of ferroptosis regulators (glutathione peroxidase 4/ferroptosis suppressor protein 1/ferritin heavy chain [GPX4/FSP1/FTH]). Secondly, Rab4 silencing amplifies exosome biogenesis via dysregulated endosomal recycling, enhancing tumor cell uptake by impairing endosome maturation-a dual-action mechanism that boosts both production and delivery. Thirdly, cRGD peptides confer αvβ3-integrin-specific targeting. cRGD-ExoM induces potent ferroptosis by increasing lipid peroxidation and downregulating GPX4/FSP1/FTH, significantly suppressing EC tumor growth in vivo without causing systemic toxicity. The platform's modular design allows for spatiotemporal control of loading, production, and targeting, demonstrating its scalability. This study provides new insights into the precision treatment of endometrial cancer by developing engineered, multifunctional, exosome-based therapeutic drugs that combine mechanism precision and translational feasibility in tumor treatment.
PURPOSE:Multidrug resistance (MDR) remains a severe challenge in the field of cancer treatment.Herein, two types of drug delivery system based on heparin named as H-F-DOX NPs (NPs-1) and H-F-Tat-DOX NPs (NPs-2) are demonstrated for efficiently reversing MDR. METHODS:NPs-1 and NPs-2 were developed by nanoprecipitation method to use succinylatedheparin as backbone and decorated with folate-targeting ligand or dual-targeting ligands of folate combined with cell-penetrating peptide Tat to release doxorubicin (DOX) for reversing MDR in A2780/R (ovarian doxorubicin-resistant cell line) and HCT-8/R (colorectal doxorubicin-resistant cell line). Cellular uptake assay, colocalization study, rhodamine 123 accumulation and cellular uptake mechanism were detected by flow cytometry and laser confocal microscope. The expression of P-gp was estimated by western blotting. Detection of intracellular adenosine triphosphate (ATP) level and reactive oxygen species (ROS) level were evaluated by luminescence assay and flow cytometry. RESULTS:The results of cytotoxicity, cellular uptake, colocalization, and detection of intracellular level of ATP and ROS level elucidated that NPs-2 could efficiently enter A2780/R and HCT-8/R cells through dual-targeting of cell penetrating peptide and folate, release more DOX into nucleus by the inhibition of drug efflux, significantly increase ROS level and reduce production of ATP level for inhibiting the proliferation of A2780/R and HCT-8/R cells. It is worth noting that the reversal coefficients of NPs-2 in A2780/R and HCT-8/R were 7.47 and 9.86. The endocytosis of NPs-2 in A2780/R and HCT-8/R depend on energy-dependent endocytosis, lipid raft and caveolae for efficient uptake and ATP production reduction. CONCLUSIONS:It demonstrates that NPs-2 could efficiently reverse MDR of ovarian and colorectal cancer in vitro. This strategy provides a novel approach by increasing endocytosis-mediated efficient cellular uptake and reducing energy production to construct smart drug delivery systems for reversing MDR.
Antibody-drug conjugates (ADCs) represent a breakthrough in tumor-targeted therapy, showing promise in both solid tumors and hematological malignancies. By 1 September 2025, more than 370 ADC candidates had entered clinical development, 17 unique products had received at least one regulatory approval worldwide, and more than 150 candidates had been discontinued. This study analyzes 3,077 ADC trials from Citeline Trialtrove, revealing that most trials are concentrated in the United States and China. At the data cutoff, 35
Neutrophils are the primary immune cell type present within the blood and the first to arrive at sites of inflammation. As such, neutrophils set the stage for how the inflammatory response progresses and resolves. In some cases of non-resolving inflammation, excessive neutrophil accumulation can cause tissue damage. Accordingly, maintaining tight control over their recruitment and behavior at sites of inflammation is paramount. Historically, corticosteroids have been used to modulate inflammation, but they are associated with systemic side effects that have limited their use. Here, we developed an iron-dexamethasone nanoparticle (DexOx NP) therapeutic that modulates neutrophil behavior and reroutes neutrophils away from sites of inflammation. DexOx NPs inhibit neutrophil activation, as indicated by prevention of L-selectin shedding and reduced neutrophil extracellular trap formation. Furthermore, treatment with DexOx NPs in a murine acute lung injury model significantly reduced the total number of neutrophils in the bronchoalveolar lavage fluid while avoiding the side effects of systemic soluble dexamethasone phosphate delivery. Thus, DexOx NPs represent a new option to control non-resolving neutrophilic inflammation.
Brain organoids provide three-dimensional human cellular systems that can reproduce selected features of early neural development, regional patterning, cellular diversification, and emerging neural activity more effectively than conventional two-dimensional cultures. However, their translational value depends not only on morphological resemblance to brain tissue, but also on whether construction strategies, functional validation, reproducibility, and application-specific model fitness are appropriately aligned. This structured narrative review synthesizes representative engineering strategies for brain organoid construction and examines how cell source, embryoid body formation, extracellular matrix support, patterning strategy, culture platform, vascularization, and cellular complexity influence functional validation and translational applicability. We further organize functional assessment into a hierarchical validation framework that includes morphology and growth, lineage and regional identity, tissue viability, synaptic maturation, electrophysiological activity, neurochemical signaling, BBB-like function, and omics-based benchmarking. These advances support the use of brain organoids in developmental biology, neurological disease modeling, drug screening, neurovascular research, and exploratory biohybrid interfaces, although their interpretation remains constrained by immature cellular states, incomplete vascular perfusion, batch variability, and limited standardization. Overall, this review reframes brain organoids as engineered biological platforms whose value should be judged by the alignment among construction strategy, biological benchmark, functional readout, and intended translational application. The emphasis is comparative conceptual synthesis of engineering strategies and multi-layer functional validation rather than systematic quantitative meta-analysis.
DNA and RNA methylation are key epigenetic and epitranscriptomic modifications involved in gene regulation, genome stability, RNA metabolism, and disease progression. Aberrant methylation patterns in cell-free DNA and RNA have emerged as valuable biomarkers for cancer detection, disease monitoring, and therapeutic stratification. However, conventional methods such as bisulfite sequencing, methylation-specific PCR, MeRIP-seq, SCARLET, and LC-MS/MS often require harsh processing, high sample input, complex instrumentation, or lack site-specific resolution, limiting their clinical and point-of-care applications. CRISPR-based diagnostics provide a promising alternative by combining programmable nucleic acid recognition with collateral cleavage-mediated signal amplification. This review summarizes recent CRISPR strategies for detecting DNA and RNA methylation, including chemical conversion-assisted assays, restriction enzyme-mediated detection, direct amplification-free sensing based on methylation-modulated Cas activity, detection of oxidized cytosine derivatives, reverse transcription-mediated Cas12 detection of m6A, and structure-sensitive Cas13 sensing. We highlight how methylation-dependent sequence conversion, enzyme accessibility, polymerase behavior, and nucleic acid structure can be translated into CRISPR-readable signals. Finally, we discuss current translational challenges and emerging opportunities in point-of-care methylation diagnostics, integrated DNA-RNA profiling, engineered Cas effectors, AI-guided assay design, and CRISPR-compatible methylome analysis.
The objective of this investigation is to develop a dressing film with a blood-repellent surface to improve hemostatic performance while minimizing excessive blood loss from absorption and potentially reducing clot-dressing adhesion. As a result, a modified technique was utilized to fabricate a hydrophobic film made of PVA and neem seed oil (NSO). The developed film underwent multiple physicochemical studies to determine its structure and properties. The films exhibited increasing hydrophobicity with neem oil incorporation, as evidenced by water contact angle values rising from 47.8° (pure PVA) to 93.56° (PVA with 4% NSO), which suggests a potential reduction in adhesion risk. Kirby-Bauer agar diffusion assays demonstrated inhibition zones of up to 14 ± 0.1 mm againstP. aeruginosa, indicating preliminary antibacterial activity. Hemostatic evaluation revealed enhanced red blood cell and platelet adhesion, with the optimized PVA/NSO (A4) film exhibiting a blood clotting index approximately 28% lower than that of the gauze control, indicating enhanced in vitro clotting efficiency compared with the gauze control. Qualitative assessment demonstrated that the films maintained good flexibility and structural integrity under bending, twisting, and stretching. Biodegradation studies showed weight loss of 25.7% for PVA/NSO films after 28 d, confirming environmental compatibility. Collectively, these results demonstrate that PVA/NSO composite films possess hydrophobicity, antibacterial activity, mechanical stability, and superior hemostatic performance, making them promising candidates for wound dressing and rapid hemostasis applications.
Piezoelectric hydrogels have emerged as a class of biomaterials that have garnered significant attention in bone tissue engineering in recent years. Their unique property lies in their ability to generate electrical charges under mechanical deformation. This piezoelectric effect is key to enhancing bone regeneration by mimicking the natural mechanical forces that stimulate osteogenesisin vivo. With their high water content, elasticity, biocompatibility, and capacity to modulate cellular responses through electrical stimulation (ES), they present an ideal choice for bone defect repair. Recent studies have demonstrated that ES can significantly promote osteoblast differentiation and bone formation, making piezoelectric hydrogels a critical factor in facilitating bone tissue regeneration. By integrating piezoelectric materials into hydrogels, they not only support cell growth but also actively promote bone healing through mechanoelectrical signaling. Specifically, this review (i) quantifies the range of piezoelectric coefficients and electrical outputs reported for hydrogels, (ii) critically compares fabrication methods with their scalability limitations, and (iii) outlines design guidelines for achieving stable, clinically translatable piezoelectric systems. By bridging materials science and bioelectric medicine, this review provides a roadmap for developing next-generation bone repair scaffolds. Unlike previous narrative reviews, our work provides a critical comparative assessment-quantitatively comparing piezoelectric coefficients, fabrication scalability, and translational bottlenecks.
Repairing osteochondral defects remains a significant clinical challenge due to the distinct requirements for regenerating both articular cartilage and the underlying subchondral bone. The goal of this study was to evaluate a multi-phase scaffold that combined melt electrowriting (MEW) and fused filament fabrication (FFF) to direct simultaneous subchondral bone and articular cartilage regeneration. To determine the optimal architecture for the chondral phase of the scaffold, an in vitro study first assessed chondrogenesis of MSCs within MEW polycaprolactone scaffolds with a range of pore sizes. All pore sizes supported cartilage-specific extracellular matrix deposition without significant differences in overall matrix accumulation. Subsequently, a hybrid scaffold was fabricated, comprising a supportive FFF shell and a bi-zonal MEW insert featuring a 600 µm pore architecture. The osseous region of the scaffold was selectively functionalized with an osteoconductive nano-needle hydroxyapatite (nnHA) coating. These constructs were implanted into critically sized caprine osteochondral defects and evaluated after six months in vivo. Histological analysis revealed that the hybrid MEW-FFF scaffolds promoted significantly more new subchondral bone formation compared to empty controls (40.2% ± 12.9% vs. 22.2% ± 13.1%). Furthermore, the hybrid scaffold supported more continuous bone regeneration throughout the defect depth, with immunohistochemical staining for collagen type II and X suggesting endochondral bone formation. Despite the enhanced subchondral bone healing, the scaffold did not significantly improve the quality of hyaline cartilage repair within the chondral region of the defect. These findings demonstrate the potential of nnHA-coated MEW-FFF hybrid scaffolds to stimulate robust subchondral bone regeneration in osteochondral defects, while underscoring the significant challenge of achieving simultaneous high-quality regeneration of both bone and articular cartilage.
Injectable hydrogels are widely investigated as carriers for mesenchymal stem cells (MSCs); however, the influence of ionic crosslinking strategy on injectability-relevant properties and earlyin vitrocell responses remains insufficiently defined from a design perspective. In this study, alginate-based hydrogels were prepared using three ionic crosslinking approaches-internal (CaCO3/ glucono-delta-lactone (GDL)), external (CaCl2), and combined gelation-and comparatively evaluated as delivery matrices for human adipose-derived MSCs. The hydrogels were characterized in terms of microstructural features, weight variation behavior, viscoelastic properties, protein diffusion, and early biological performance. Rheological analysis revealed a broad range of mechanical responses, with storage moduli varying from approximately 102-103Pa depending on the crosslinking mechanism. Internally-gelled hydrogels exhibited a softer, more deformable network and a wider linear viscoelastic region, while externally and double-crosslinked hydrogels showed increased stiffness but more brittle behavior. Microstructural observations indicated larger and more interconnected pores in internally crosslinked systems compared to the denser networks formed via external gelation.In vitrobiological assessments, including metabolic activity, DNA quantification, and post-injection viability, demonstrated that the crosslinking strategy significantly affected early cell fate. Notably, internally-crosslinked hydrogels supported higher cell viability and metabolic activity while maintaining superior post-injection cell survival (>95%), whereas double-crosslinked hydrogels showed lower viability following syringe delivery consistent with their higher stiffness and lower deformation tolerance. Overall, this comparative study highlights the trade-offs between mechanical integrity, handling during syringe delivery, and early biological performance in ionically-crosslinked alginate hydrogels. The findings provide practical design-oriented guidance for selecting alginate crosslinking strategies in injectable MSCs delivery systems where minimally invasive administration and early cell survival are critical considerations.
The worldwide incidence of bone disorders is increasing at an alarming rate, especially among the elderly and those with increased obesity and poor physical activity. Therefore, bone tissue engineering, the process of regenerating diseased or damaged bone, is gaining increasing attention from the scientific community. One of the critical components for tissue engineering is the scaffold, an artificial extracellular matrix that promotes bone formation and regeneration activities. Due to the increasing demands for bone repair, bone tissue scaffolds have been extensively studied in state-of-the-art literature. Nevertheless, many areas related to scaffold manufacturing still offer huge scope for scientific research and development. One such area is the bioprinting of scaffolds, which combines the advantages of three-dimensional printing and biomaterials to create an ideal tissue growth support environment for bone tissue regeneration. This review highlights recent advances in the bioprinting of scaffolds for bone tissue engineering. Taking different biomaterial-based scaffolds as a starting point, the latest research progress and breakthrough points for enhancing the mechanical properties and bioactivities of scaffolds are summarized. Recent scientific breakthroughs related to the tailoring and creative design of scaffolds have been highlighted. New strategies and schemes for subsequent bone scaffold angiogenesis and osteogenesis promotion for new bone tissue regeneration are also discussed. This comprehensive review identifies the shift of research direction, where the biological requirements such as immune response and vascularization is prioritized over fabrication methods. Research gaps on vascularization bottlenecks, methodological and evaluation gaps, fabrication challenges and regulatory hurdles have been identified as well. Future direction of research includes AI assisted design, 4D printing, smart implants, organoid integration and benchmarking standardization of bone tissue implants.
Fertility preservation for women undergoing gonadotoxic treatments remains a critical clinical challenge. Ovarian tissue(OT) cryopreservation and transplantation are promising strategies. This review aims to map the biomaterials used in OT culture and cryopreservation, identify key knowledge gaps, and outline future research directions. Following the Arksey&O'Malley (2005) framework and the PRISMA-ScR guidelines, a literature search was conducted on PubMed and Web of Science. The review protocol was prospectively registered on the Open Science Framework (OSF.IO/NRZM7). Of 3,217 studies, 41 were included in the analysis: 32 were in vivo studies, 8 were in vitro, and 1 was clinical. The main biomaterials used for OT culture and cryopreservation included fibrin, alginate, collagen, hyaluronic acid, and extracellular matrix. Key preservation strategies involve encapsulating OT within biomaterial-based systems and enriching culture media with biomaterials. Hydrogels have demonstrated advantages by providing structural scaffolding and facilitating the diffusion of oxygen, nutrients, and bioactive supplements, thereby promoting angiogenesis and supporting OT functional restoration. Growing interest was noted in combinatorial approaches that integrate multiple biomaterials with stem cells, plasma proteins, and growth or antioxidant factors to enhance folliculogenesis and restore oestrous cycles. Despite progress, critical challenges persist, including capsule disintegration and the associated risk of immune sensitisation, as well as limited understanding of long-term tissue revascularisation and OT-biomaterial interactions. Overall, biobased materials strategies, particularly hydrogels, show promise for improving OT preservation and functionality, but further research is needed to optimise these materials and understand their long-term implications for fertility outcomes. Among the included studies, only one was a clinical study; the rest consisted of in vivo animal models and in vitro experiments. This limitation should be recognised, as it prevents direct application of the results to clinical practice. Consequently, further clinical research is crucial to confirm these strategies and facilitate their safe and effective implementation in fertility preservation protocols.
Scaffold-based periodontal tissue engineering offers a promising strategy for regenerating tissues destroyed by periodontitis, for which conventional treatments fall short. An ideal scaffold must not only possess good biocompatibility to establish a regenerative microenvironment but also address the complex pathological features of periodontitis, including persistent bacterial infection, hyperactive immune-inflammatory responses, and the demand for bone defect repair. Natural marine polysaccharides (such as alginate, carrageenan, fucoidan, chitin and its derivatives, and hyaluronic acid) exhibt excellent biocompatibility and degradability, along with inherent antibacterial, anti-inflammatory, immunomodulatory, and osteogenic properties, making them highly suited to the pathological demands of periodontal regeneration. Although these five classes of materials differ in chemical composition, they all combine intrinsic bioactivity with abundant modifiable sites, making them an ideal platform for constructing multifunctional periodontal regeneration scaffolds. Based on this, this review focuses on the microstructural characteristics and structure-activity relationships of marine polysaccharide, systematically summarizing their applications and research progress in the design of periodontal tissue regeneration scaffolds.
