Tissue engineering and regenerative medicine最新文献

Background: Underwater adhesion of polymeric adhesives is highly desirable in specific applications such as wound dressings, wearable devices, bioelectronic devices, biosensors, and water pipeline leakage repairing. However, underwater bonding is considerably different from bonding in air because interfacial water molecules substantially weaken the intimate contact adhesion between the adhesive and submerged surfaces, thus significantly limiting the application of adhesives in various fields.

Method: This review was compiled by searching relevant references on PubMed database (before April 2025) based on selected keywords.

Results: Recently, many wet adhesion technologies and diverse and flexible adhesive materials have been employed to address the weak adhesion strengths and inferior mechanical properties in underwater environments. Among several strategies, mussel-inspired catechol-based underwater adhesion has gained the attention of scientists because mussel-inspired tissue adhesives (TAs) demonstrate numerous advantages including many interactions with substrates, various designs of some interesting smart TAs, and excellent adhesion based on several interfacial interactions dominated by 3,4-dihydroxyphenylalanine, a catecholic amino acid in mussel adhesive proteins.

Conclusion: We discuss the mechanism of catechol-based underwater adhesion, classification of underwater adhesives, and characteristics, applications, advantages, and disadvantages of dopamine (DA)-modified polymeric TAs. Furthermore, we review stimuli-responsive TAs and the essential factors affecting the adhesions of DA-modified TAs in underwater environments. Finally, we discuss some current technical challenges and future perspectives for underwater adhesion.

Background: Dental pulp stem cells (DPSCs) are critical for periodontal tissue regeneration, yet their therapeutic potential is limited by suboptimal osteogenic differentiation. Liraglutide (LIRA), a glucagon-like peptide-1 receptor agonist, exhibits anti-inflammatory and bone-protective properties. This study aimed to investigate the modulatory effects of LIRA on DPSCs proliferation and osteogenic differentiation.

Methods: DPSCs were treated with LIRA to assess proliferation and osteogenic differentiation using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine staining, alkaline phosphatase (ALP), and alizarin red S (ARS) assays. Histone lactylation levels (total lactylation and H3K18la) were quantified by Western blot. Chromatin immunoprecipitation (ChIP) and dual-luciferase assays evaluated H3K18la enrichment at the dentin sialophosphoprotein (DSPP) promoter. DSPP overexpression was used in rescue experiments to validate the role of the H3K18la-DSPP axis.

Results: LIRA significantly enhanced DPSC proliferation and osteogenic differentiation, as evidenced by increased ALP activity, mineralization nodules, and upregulated osteogenic markers (DMP1, DSPP, RUNX2, OCN, OPN). LIRA elevated global lactylation and H3K18la levels, with ChIP assays showing H3K18la enrichment specifically at the DSPP promoter. Dual-luciferase and RT-qPCR confirmed LIRA-induced DSPP transcriptional activation. Oxamate reversed LIRA's effects, while Nala amplified them. DSPP overexpression rescued oxamate-mediated suppression of osteogenesis, confirming the H3K18la-DSPP regulatory mechanism.

Conclusion: This study demonstrates that LIRA promotes DPSC osteogenesis via histone lactylation-mediated DSPP transcriptional activation. The H3K18la-DSPP axis represents a novel metabolic-epigenetic pathway for enhancing periodontal regeneration.

Background: Achilles tendon injuries are among the most common lower-body tendon injuries, often resulting fromoveruse and repetitive motion. Current treatments, ranging from conservative therapies to biological grafts, have drawbacks, including limited regenerative capacity and the risk of graft rejection. To overcome these challenges, tissue engineering shows growing promise for Achilles tendon regeneration, with ongoing research focused on developing biomimetic constructs that utilize various materials and biologics. Since every tendon has unique biomechanical and physiological characteristics, it is crucial to conduct individualized evaluations through detailed research and to address key considerations for clinical translation.

Methods: This review focuses explicitly on advances in Achilles tendon tissue engineering for human medicine, assessing constructs made from natural, synthetic, and composite materials with/without biologics and discussing their clinical translation. Studies were searched in the PubMed database and Google Scholar, using the most relevant keywords, such as "Achilles tissue engineering", "Achilles biomimetic constructs", "Biomaterials for Achilles tendon", and "Clinical translation".

Results: Biomimetic constructs developed from various polymers and their combinations, when integrated with stem cells, demonstrate promising potential to reconstruct tissue microenvironments in vitro and to facilitate tissue repair and biomechanical functions in vivo. Carefully developing each element, including appropriate material structures, is essential for optimizing cell responses, biomechanical properties, and tissue repair in the Achilles tendon. Although the in vitro and in vivo advances reviewed in the paper contribute to clinical research, further studies with reproducible, long-term outcomes are needed to make the constructs clinically applicable in human medicine.

Conclusion: Achilles tissue engineering continues to progress, driven by a deeper understanding of the injuries and the integration of regenerative tools. Furthermore, clinical considerations, such as long-term in vivo follow-up to assess biocompatibility and functional recovery, will be critical to achieving clinical outcomes.

Background: Regenerative cell sources such as bone marrow-multipotent stem cells (BM-MSCs) face poor survival after transplantation due to shear stress and anoikis in attachment-deprived conditions. Cell surface modification with type I collagen (Col I) may enhance cell survival in anoikis-inducing environment by mimicking cell-ECM interactions and activating Akt signaling. However, the relative contributions of biochemical versus mechanical signalling remain unclear.

Methods: BM-MSCs were surface-modified with 2, 4, or 8 layers (L) of Col I and cultured on poly-2-hydroxyethyl methacrylate-coated vessels for 3 days. Col I retention, Akt activation, and cytoskeletal changes were analyzed by immunofluorescence. YAP nuclear translocation was measured to assess mechanotransduction.

Results: Col I persisted up to 10 h in 4L and 8L groups but not in 2L. All surface-modified groups showed membrane-localized Akt phosphorylation, while controls did not. Only the 8L group demonstrated significant anoikis resistance from day 1, exhibiting distinct ring-like actin arrangement within 2 h and enhanced YAP nuclear localization, indicating activation of mechanotransduction-associated responses.

Conclusions: All surface-modified groups showed Akt phosphorylation, indicating biochemical signaling. The 4L group exhibited significantly higher survival by day 2, suggesting sustained biochemical signaling promotes survival. The 8L group showed superior survival from day 1 with increased YAP translocation and actin reorganization, demonstrating that mechanotransduction may contribute to an early survival advantage. This cell model enables differential investigation of biochemical and mechanical effects on cell survival.

Background: Xenogeneic menisci offer a promising biomaterial with high biocompatibility, closely resembling the native meniscus. However, to enable clinical application in humans, decellularization is essential to remove cellular components that may trigger graft rejection.

Method: We developed a combined decellularization protocol for bovine-derived meniscus tissue, integrating physical stimulation (sonication and vacuum), chemical treatments (hypotonic and hypertonic solutions, and sodium dodecyl sulfate [SDS]), and enzymatic digestion (trypsin and nucleases). The decellularization efficiency was confirmed not only by DNA reduction rate, but also by residual DNA, DNA fragmentation and histology. Subsequently, cytotoxicity, biocompatibility, and mechanical properties were assessed.

Results: This combined decellularization achieved a DNA removal efficiency of up to 94.94%, enabled rapid decellularization within 5 days, and preserved collagen content, resulting in a high-quality xeno meniscal implant (XMI).

Conclusion: The XMI produced through this combined decellularization process demonstrates strong potential as a scaffold for the treatment of meniscal injuries.

Background: Organoids are three-dimensional (3D) in vitro cell culture systems that grow and self-organize, with cells differentiating into functional types and forming miniature structures that replicate the architecture and function of in vivo organs. While the need for standardized organoid culture systems has been widely emphasized, the production of functionally complex and scalable lung organoids remains a significant challenge.

Methods: Here, we present a scalable lung organoid production platform using a 96-deep-well format with organoids derived from induced pluripotent stem cells (iPSCs). iPSCs were first differentiated into definitive endoderm (DE), followed by anterior foregut endoderm (AFE) in a two-dimensional (2D) culture system. The AFE cells were then transferred into deep wells to generate alveolar epithelial cells (AECs), and subsequently differentiated into SFTPA-positive lung cells within 3D organoids over a 15-day period.

Results: This new culture platform enables single cells to self-organize into organoids in a serum-free, antioxidant-enriched medium using a 96-deep-well plate. Compared to conventional organoid culture methods, this system significantly improves the consistency, uniformity, and reproducibility of organoid formation.

Conclusion: Notably, organoids generated in deep wells are functionally comparable to those cultured in Matrigel, but offer enhanced uniformity-an essential improvement for reliable drug screening applications.

Background: Alkaline phosphatase (ALP) is a well-established molecular marker of dermal papilla (DP) cells, and its activity closely correlates with their hair-inductive (trichogenic) capacity. This study aimed to identify downstream effectors regulated by ALP that contribute to trichogenicity, and to validate their functional significance in hair follicle neogenesis.

Methods: A cytokine array was employed to screen ALP-dependent secreted factors in three-dimensional (3D) cultured human DP spheres. The expression of C-C motif chemokine ligand 5 (CCL5) and its receptor C-C chemokine receptor type 1 (CCR1) was confirmed by quantitative real-time PCR and immunohistochemistry in human hair follicles and murine skin. Functional roles of CCL5 in DP spheres and CCR1 in mouse epidermal cells were evaluated using siRNA-mediated knockdown followed by in vivo patch hair regeneration assays.

Results: ALP knockdown significantly reduced CCL5 expression in DP spheres. Silencing of CCL5 in DP spheres markedly decreased their hair-inductive capacity, while CCR1 knockdown in epidermal cells impaired hair follicle formation. Combined knockdown of CCL5 in DP cells and CCR1 in epidermal cells completely abolished hair follicle neogenesis.

Conclusion: These findings identify CCL5 as a critical downstream mediator of ALP-regulated trichogenicity in human DP spheres, with CCR1 serving as its essential receptor in epidermal cells. The ALP-CCL5-CCR1 axis represents a promising therapeutic target for promoting hair regeneration.

Background: The tumor microenvironment (TME) is a major obstacle to effective cancer therapy, driving tumor progression, metastasis, and resistance to conventional treatments. Mesenchymal stem cells (MSCs) have attracted increasing interest as therapeutic vehicles due to their intrinsic tumor-homing capability; however, the therapeutic efficacy of unmodified MSCs remains limited.

Methods: This review examines recent engineering strategies for enhancing MSC therapeutic functionality in TME modulation and precision cancer therapy. Relevant literature was surveyed with focus on nanotechnology-enabled approaches. We analyze key TME features including hypoxia, immunosuppression, and physical barriers, and how various engineering strategies address these challenges.

Results: Engineered MSCs have been successfully transformed into therapeutic "bio-factories" through genetic modification, enabling sustained secretion of cytokines, enzymes, or therapeutic proteins. In parallel, payload-based strategies have established MSCs as effective "Trojan horse" carriers for nanomaterials, chemotherapeutic agents, and oncolytic viruses, allowing precise delivery and active remodeling of the TME. These approaches collectively enhance tumor targeting, therapeutic efficacy, and spatial control within solid tumors.

Conclusion: The integration of MSC biology with nanotechnology provides a powerful platform for regulating the TME and achieving precision oncology. While challenges related to safety, protumorigenic effects, and manufacturing scalability remain, recent advances are rapidly addressing these barriers. Engineered MSC-based therapies hold great promise to revolutionize cancer treatment and overcome the longstanding challenges of solid tumor therapy.

Background: Sensorineural hearing loss caused by ototoxic agents remains irreversible due to the limited regenerative capacity of cochlear hair cells. Exosome-based therapies derived from mesenchymal stem cells (MSCs) offer a promising, cell-free alternative to protect auditory structures by modulating oxidative stress and inflammation. In this study, we evaluated the therapeutic potential of exosomes isolated from nanoparticle (NP) labeled, N-acetylcysteine primed tonsil-derived mesenchymal stem cells (T-MSCs), hereafter referred to as SPISOME-NAC, in kanamycin-induced ototoxicity models.

Methods: T-MSCs were labeled with positively charged PLGA-PEI clustered SPIONs, with or without NAC pretreatment. Antioxidant enzyme activity (SOD, CAT, GSH), ROS levels, and PRDX1 expression were assessed in vitro. Exosomes were isolated and analyzed via nanoparticle tracking analysis. Their therapeutic efficacy was evaluated in both ex vivo cochlear explants and mouse model of kanamycin-induced ototoxicity. Hair cell survival was quantified via Myosin VIIa immunostaining, and auditory function was assessed using auditory brainstem responses (ABR). Pro-inflammatory cytokines (TNF-α, IL-1, IL-6) were measured via qRT-PCR.

Results: NAC pretreatment significantly enhanced cell viability, increased GSH activity, and reduced intracellular ROS and PRDX1 levels in NP-labeled T-MSCs. Exosomes derived from NAC-pretreated cells (SPISOME-NAC) conferred superior protection to cochlear hair cells, particularly in the basal turn, and significantly improved hearing thresholds in vivo. Furthermore, SPISOME-NAC treatment downregulated inflammatory cytokines in cochlear tissue.

Conclusion: SPISOME-NAC exhibit enhanced antioxidant and anti-inflammatory properties, providing functional protection in an ototoxicity-induced hearing loss model. By preventing ROS-mediated mitochondrial damage and apoptosis in cochlear hair cells, NAC interrupts a key pathogenic mechanism in ototoxicity, preserving auditory structure and function. These findings support NAC-primed exosomes as a novel therapeutic strategy for sensorineural hearing loss.