Regenerative Medicine Research Articles

Densely vascularized thick 3D tissue shows enhanced protein secretion constructed with intermittent positive pressure

Constructing a dense vascular endothelial network within engineered tissue is crucial for successful engraftment. The present study investigated the effects of air-compressing intermittent positive pressure (IPP) on co-cultured mesenchymal stem cells and vascular endothelial cells and evaluated the potential of IPP-cultured cell sheets for transplantation therapy. The results demonstrated that the IPP (+) group exhibited a denser vascular endothelial network and significantly increased cell sheet thickness compared to the IPP (-) group. Furthermore, in vivo experiments showed that IPP-cultured cell sheets enhanced the secretion of Gaussian luciferase by genetically modified mesenchymal stem cells. These findings highlight the IPP method as a technique that simultaneously enables the thickening of planar tissues and the construction of vascular networks. This approach demonstrates promise for fabricating functional, transplantable, and thick tissues with dense vascularization and a high capacity for protein secretion, paving the way for novel applications in regenerative medicine.

Recent advances in electrochemiluminescence sensing for in vitro cell analysis: a review.

Electrochemiluminescence (ECL) is a chemiluminescence phenomenon triggered by electrochemical reactions and is widely used for (bio)chemical analyses and electrochemical bioimaging. Compared to fluorescence sensing, ECL sensing reduces background noise by eliminating autofluorescence associated with excitation light. In addition, compared with conventional electrochemical imaging with scanning electrochemical microscopes, ECL imaging is faster as it requires no scanning. Furthermore, unlike electrode arrays, ECL devices can function without complex wiring, simplifying their construction. These characteristics render ECL sensing a useful analytical tool. Recently, ECL sensing has been widely used for in vitro cell analysis due to high demand for biochips in regenerative medicine, drug screening, and microphysiological systems. This review focuses on recent advancements in ECL-based cell analysis with applications for the detection of H2O2, respiration activity, cell adhesion, lipid membranes, and bipolar electrochemistry-based devices.

Therapeutic Reprogramming toward Regenerative Medicine.

Therapeutic reprogramming represents a transformative paradigm in regenerative medicine, developing new approaches in cell therapy, small molecule drugs, biologics, and gene therapy to address unmet medical challenges. This paradigm encompasses the precise modulation of cellular fate and function to either generate safe and functional cells ex vivo for cell-based therapies or to directly reprogram endogenous cells in vivo or in situ for tissue repair and regeneration. Building on the discovery of induced pluripotent stem cells (iPSCs), advancements in chemical modulation and CRISPR-based gene editing have propelled a new iterative medicine paradigm, focusing on developing scalable, standardized cell therapy products from universal starting materials and enabling iterative improvements for more effective therapeutic profiles. Beyond cell-based therapies, non-cell-based therapeutic strategies targeting endogenous cells may offer a less invasive, more convenient, accessible, and cost-effective alternative for treating a broad range of diseases, potentially rejuvenating tissues and extending healthspan.

Leveraging stringency and lifecycle thinking to advance environmental sustainability in health technology regulation.

Regulatory actors, particularly market authorization agencies, health technology assessment agencies, and health care procurement agencies, exert a powerful influence on the adoption and use of health technologies (eg, medicines and medical devices). With health care being responsible, directly and indirectly, for an estimated 4.6% of global greenhouse gas emissions, alongside other environmental harms, these actors have recognized the need to address the environmental impacts of health technologies. In this commentary, we utilize concepts of regulatory stringency and lifecycle thinking, considering scope, prescriptiveness, and performance requirements, to analyze recent efforts to incorporate environmental sustainability into the regulation of medicines and medical devices. While we acknowledge recent progress, we argue that there is significant, untapped potential for developing more fulsome and effective regulatory mechanisms to improve the environmental sustainability of health technologies.

Beyond Earth’s Gravity: Navigating Legal Hurdles in Space-Based Drug Research and Development

For over 20 years, scientists aboard the International Space Station (the “ISS”) have been expanding the boundaries of scientific knowledge. Leveraging microgravity and other extreme conditions unique to space, these scientists have made significant discoveries in cellular behavior, tissue engineering, gene expression, organism growth patterns, and regenerative medicine. This article aims to introduce the pharmaceutical and biotechnology communities to the exciting possibilities and challenges of conducting research and development (“R&D”) in space. The scientific advantages of space-based drug R&D are compelling. Experiments conducted aboard the ISS National Lab, along with ground-based studies, reveal unique features that cannot be replicated under normal gravity conditions. For instance, space-based drug research has shown that microgravity conditions enable more efficient 3D cell cultures, improved protein crystal growth, and open up new possibilities for 3D printing of biomaterials, cells, tissues, and organs.

Unveiling the native architecture of adult cardiac tissue using the 3D-NaissI method

Accurately imaging adult cardiac tissue in its native state is essential for regenerative medicine and understanding heart disease. Current fluorescence methods encounter challenges with tissue fixation. Here, we introduce the 3D-NaissI (3D-Native Tissue Imaging) method, which enables rapid, cost-effective imaging of fresh cardiac tissue samples in their closest native state, and has been extended to other tissues. We validated the efficacy of 3D-NaissI in preserving cardiac tissue integrity using small biopsies under hypothermic conditions in phosphate-buffered saline, offering unparalleled resolution in confocal microscopy for imaging fluorescent small molecules and antibodies. Compared to conventional histology, 3D-NaissI preserves cardiac tissue architecture and native protein epitopes, facilitating the use of a wide range of commercial antibodies without unmasking strategies. We successfully identified specific cardiac protein expression patterns in cardiomyocytes (CMs) from rodents and humans, including for the first time ACE2 localization in the lateral membrane/T-Tubules and SGTL2 in the sarcoplasmic reticulum. These findings shed light on COVID-19-related cardiac complications and suggest novel explanations for therapeutic benefits of iSGLT2 in HFpEF patients. Additionally, we challenge the notion of "connexin-43 lateralization” in heart pathology, suggesting it may be an artifact of cardiac fixation, as 3D-NaissI clearly revealed native connexin-43 expression at the lateral membrane of healthy CMs. We also discovered previously undocumented periodic ring-like 3D structures formed by pericytes that cover the lateral surfaces of CMs. These structures, positive for laminin-2, delineate a specific spatial architecture of laminin-2 receptors on the CM surface, underscoring the pivotal role of pericytes in CM function. Lastly, 3D-NaissI facilitates the mapping of native human protein expression in fresh cardiac autopsies, offering insights into both pathological and non-pathological contexts. Therefore, 3D-NaissI provides unparalleled insights into native cardiac tissue biology and holds the promise of advancing our understanding of physiology and pathophysiology, surpassing standard histology in both resolution and accuracy.

Regulation of stem cell function by NAD.

Nicotinamide adenine dinucleotide (NAD+), a coenzyme in cellular metabolism, has never ceased to capture the fascination of scientists since its discovery in 1906. The expansion of NAD+’s function from cellular metabolism to DNA repair, gene regulation, cell signaling, and aging reflects the central role of cellular metabolism in orchestrating the diverse cellular pathways. In the past decade, NAD+ has emerged to be a key regulator of stem cells, opening the door to potential approaches for regenerative medicine. Here we reflect on how the field of NAD+ regulation of stem cells has evolved since a decade ago, when sirtuins, NAD+-dependent enzymes, were shown to be critical regulators of stem cells. We review the recent development on how NAD+ is regulated in stem cells to influence fate decision. We discuss the difference in NAD+ regulation of normal and cancer stem cells. Finally, we consider the consequences of NAD+ regulation of stem cells for health and diseases.

Biomimetic Hydrogels - Tools for Regenerative Medicine, Oncology, and Understanding Medical Gas Plasma Therapy.

Biomimetic hydrogels enable biochemical, cell biology, and tissue-like studies in the third dimension. Smart hydrogels are also frequently used in tissue engineering and as drug carriers for intra- or extracutaneous regenerative medicine. They have also been studied in bio-sensor development, 3D cell culture, and organoid growth optimization. Yet, many hydrogel types, adjuvant components, and cross-linking methods have emerged over decades, diversifying and complexifying such studies. Here, an evaluative overview is provided, mapping potential applications to the corresponding hydrogel tuning. Strikingly, hydrogels are ideal for studying locoregional therapy modalities, such as cold medical gas plasma technology. These partially ionized gases produce various reactive oxygen species (ROS) types along with other physico-chemical components such as ions and electric fields, and the spatio-temporal effects of these components delivered to diseased tissues remain largely elusive to date. Hence, this work outlines the promising applications of hydrogels in biomedical research in general and cold plasma science in particular and underlines the great potential of these smart scaffolds for current and future research and therapy.

Exploring medicine classification and accessibility: a qualitative study.

Brunei Darussalam's medicine control governance landscape is complex, driven by legislative directives and directed by the Brunei Darussalam Medicines Control Authority (BDMCA). While the medicine dispensing system in Brunei Darussalam, across both governmental and private sectors, is a critical component of the nation's healthcare, it remains under-researched, leaving gaps in understanding its distinctions, challenges, and opportunities. This study aimed to explore deep into the perspectives of pharmacists regarding the medicine dispensing systems in Brunei Darussalam, medicine accessibility, the classification and regulation of medicines, and the growing role of pharmacists. Using a narrative qualitative approach, we conducted in-depth one-on-one interviews with six pharmacists, delving into their personal experiences with topics such as medicine classification and the broader systems for medication provision. The collected narratives were analysed through a rigorous thematic analysis, following the framework established by Braun & Clarke. Five themes emerged from the data: nuances of Brunei Darussalam's medicine dispensing landscape across both public and private sectors; accessibility and regulatory framework of medicines both in Brunei Darussalam and abroad; prospective implementations to enhance the current system; and the evolving role and expectations of pharmacists in the current healthcare environment. Notably, a significant contribution of this study was the illumination of the differential perspectives between pharmacists operating in governmental versus private contexts. This study sheds light on the previously under-explored domain of Brunei Darussalam's medicine control governance and medicine dispensing system. By drawing from the first-hand experiences of practicing pharmacists, it offers actionable insights that could guide future policy developments, optimise medicine dispensation and regulation, and shape the evolving role of pharmacists in Brunei Darussalam.

DCE-MRI Detects OATP-expressing Transplanted Cells Using Clinical Doses of Gadolinium Contrast Agent.

Hepatic organic anion transporting polypeptides (OATPs) transport off-the-shelf, FDA-approved, hepatospecific Gd-based MRI contrast agents into cells that express the transporters enhancing signal on T1-weighted MRI. Studies have used MRI to identify OATP-overexpressing tumors and metastases transplanted in mice following the delivery of Gd-EOB-DTPA at 27-67-fold higher than clinical doses. With safety and regulatory concerns over Gd-based contrast agents, translating OATPs as an MRI reporter protein to humans for regenerative medicine will require substantially lower doses of agent. We engineered the MyC-CaP mouse tumor cell line to express rat OATP1B2, which influxes both Gd-EOB-DTPA and Gd-BOPTA, resulting in signal enhancement on T1-weighted MRI. We then inoculated mice with rat OATP1B2 and non-expressing cells bilaterally to generate tumors. 3-4weeks after inoculation, when tumors had formed, in-vivo MRI imaging was performed with delivery of 0.025mmol/kg or 0.25mmol/kg of the Gd-based contrast agents. We complemented static T1-weighted MRI and T1-mapping with dynamic contrast enhanced (DCE)-MRI and performed area under the curve (AUC) analysis to discriminate the two tumor types. While all OATP1B2-expressing tumors were easily visible at the high dose of 0.25mmol/kg on T1-weighted MRI and easy to distinguish from control tumors, OATP1B2-expressing tumors were hard to identify and distinguish from non-expressing tumors at the lower, clinical dose of 0.025mmol/kg with standard T1-weighted MRI or T1-mapping. However, AUC analyses of the DCE-MRI curves could identify and distinguish these tumors, needing 30 (Gd-EOB-DTPA) or 45 (Gd-BOPTA) minutes acquisition time. By performing AUC analyses of DCE-MRI curves following delivery of clinical concentration of MRI contrast agents, OATP1B2-expressing tumors could be identified and distinguished from control tumors, suggesting this imaging approach as a path to substantially reducing the amount of contrast agent needed to use OATPs as a clinically viable reporter protein for imaging regenerative medicine.

Functionalized conductive polymer composites for tissue engineering and biomedical applications- a mini review

Tissue engineering (TE) has emerged as a promising therapeutic strategy, employing artificial scaffolds to regenerate functional cardiac tissue and offering new hope for innovative treatment approaches. A straightforward method for producing biodegradable, conductive polymer-based composites involves blending conductive polymers directly with biodegradable ones. This approach’s flexibility enables the development of diverse biodegradable, conductive polymer scaffolds, which have been extensively explored in tissue engineering and regenerative medicine. While this technique successfully combines the advantages of both polymer types, it may face challenges such as potential compromises in conductivity and biodegradability. This review emphasizes the potential to tailor degradation rates and conductivity by selecting appropriate polymer types and ratios, ensuring adaptability for various biomedical applications.

Advancements in lung regeneration: from bench to bedside.

Lung disorders rank among the leading causes of mortality worldwide, presenting a critical challenge in healthcare. The underlying limited regenerative capacity of the lung makes this an unmet clinical need, often necessitating lung transplantation for patients with severe lung disease. However, the lack of viable donor organs underscores the urgent need for alternative therapeutic strategies. Addressing this challenge requires a comprehensive understanding of the structure of lung tissue and the complexities inherent in its regeneration. In this review, we explore recent breakthroughs in lung regenerative medicine, highlighting innovative approaches aimed at tackling lung and tracheal diseases. From stem cell and cell-based therapies to the utilization of biological and synthetic materials, as well as the strategic deployment of growth factors, a diverse array of strategies is being explored to rejuvenate lung function. By critical analysis of in vitro, preclinical, and clinical studies, this review aims to provide a comprehensive overview of the emerging technology of lung regeneration research, shedding light on promising avenues for future therapeutic interventions.

The Role of Bioactive Glasses in Modern Dentistry: From Remineralization to Regeneration

Aim: This review explores the potential of bioactive glasses in dentistry, focusing on their applications in dental restorations, implants, and tissue regeneration. The aim is to assess the challenges and opportunities in their use, as well as the future directions for enhancing their performance. Materials and Methods: A comprehensive review of recent literature was conducted to analyze the properties, applications, and limitations of bioactive glasses in dental materials. Studies on the composition, mechanical properties, biocompatibility, and long-term in vivo performance were included. Methods to enhance the mechanical strength of bioactive glasses, such as the formation of composites and advanced nano structuring, were also explored. Results: Bioactive glasses have shown great promise in promoting remineralization, supporting tissue regeneration, and bonding with hard tissues. However, challenges such as mechanical brittleness, high costs, and limited long-term stability have been identified. Research on enhancing mechanical strength through composites, as well as developing more cost-effective production methods, is ongoing. Conclusion: Bioactive glasses offer significant potential for improving dental treatments and advancing regenerative medicine. Future research should focus on enhancing their mechanical properties, developing personalized bioactive materials, and exploring their integration with stem cell therapies and growth factors. With continued development, bioactive glasses could revolutionize dental restorations, implants, and oral tissue regeneration, providing innovative solutions for oral healthcare.

Signaling Pathways Driving MSC Osteogenesis: Mechanisms, Regulation, and Translational Applications

Mesenchymal stem cells (MSCs) are crucial for skeletal development, homeostasis, and repair, primarily through their differentiation into osteoblasts and other skeletal lineage cells. Key signaling pathways, including Wnt, TGF-β/BMP, PTH, Hedgehog, and IGF, act as critical regulators of MSC osteogenesis, playing pivotal roles in maintaining bone homeostasis and facilitating regeneration. These pathways interact in distinct ways at various stages of bone development, mineralization, and remodeling. This review provides an overview of the molecular mechanisms by which these pathways regulate MSC osteogenesis, their influence on bone tissue formation, and their implications in bone diseases and therapeutic strategies. Additionally, we explore the potential applications of these pathways in bone tissue engineering, with a particular focus on promoting the use of MSCs as seed cells for bone defect repair. Ultimately, this review aims to highlight potential avenues for advancing bone biology research, treating bone disorders, and enhancing regenerative medicine.

Constructing a potential HLA haplo-homozygous induced pluripotent stem cell haplobank using data from an umbilical cord blood bank

BackgroundInduced pluripotent stem cells (iPSCs) can differentiate into any type of cell and have potential uses in regenerative medicine for the treatment of many diseases. However, reducing immune rejection is a key problem in the application of iPSCs that can be solved by the development of haplobanks containing specially selected iPSC lines.MethodsTo study the feasibility of constructing an HLA (human leukocyte antigen)-matched induced pluripotent stem cell haplobank in China, 5421 umbilical cord blood samples were randomly collected from the Umbilical Cord Blood Bank of Zhejiang Province, China. The HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci were genotyped using next-generation sequencing. Using HLA genotype data at the high-resolution level, the number of HLA homozygous donors needed to cover a certain percentage of the Chinese population and the feasibility of constructing a high-matching iPSC haplobank were estimated.ResultsThirteen HLA-A, -B, and -DRB1 and 11 HLA-A, -B, -C, -DRB1, and -DQB1 haplotype homozygotes were observed among the stored umbilical CB units which were as HLA zero-mismatched iPSC donors cumulatively matched 37.01% and 32.99% of 5421 potential patients respectively. The analysis showed that 100 distinct HLA-A, -B, and -DRB1 and HLA-A, -B, -C, -DRB1, and -DQB1 homozygous haplotypes would cover 72.74% and 67.87% of Chinese populations, respectively, and 600 HLA-A, -B, -C, -DRB1, and -DQB1 homozygous haplotypes would cover more than 90% of Chinese populations. PCA (principal component analysis) of published HLA data from different populations revealed that the frequency of these haplotypes in Asian populations is different from those in European populations.ConclusionThe results suggested that at least some HLA-homozygous iPSC lines developed from Chinese individuals will not only be useful for covering the Chinese population but will also cover other Asian populations. A high-matching iPSC haplobank generated from umbilical CB units may be an economical and effective option in an allogeneic model of iPSC therapy.

Modulating Polyphenol Activity with Metal Ions: Insights into Dermatological Applications

Background: The skin represents the first barrier of defense, and its integrity is crucial for overall health. Skin wounds present a considerable risk seeing how their progression is rapid and sometimes they are caused by comorbidities like diabetes and venous diseases. Nutraceutical combinations like the ones between polyphenols and metal ions present considerable applications thanks to their increased bioavailability and their ability to modulate intrinsic molecular pathways. Methods: The research findings presented in this paper are based on a systematic review of the current literature with an emphasis on nanotechnology and regenerative medicine strategies that incorporate polyphenols and metallic nanoparticles (NPs). The key studies which described the action mechanisms, efficacy, and safety of these hybrid formulations were reviewed. Results: Nanocomposites of polyphenol and metal promote healing by activating signaling pathways such as PI3K/Akt and ERK1/2, which in turn improve fibroblast migration and proliferation. Nanoparticles of silver and copper have antibacterial, angiogenesis-promoting, inflammation-modulating capabilities. With their ability to induce apoptosis and restrict cell growth, these composites have the potential to cure skin malignancies in addition to facilitating wound healing. Conclusions: Nanocomposites of polyphenols and metals provide hope for the treatment of cancer and chronic wounds. Their antimicrobial capabilities, capacity to modulate inflammatory responses, and enhancement of fibroblast activity all point to their medicinal potential. Furthermore, these composites have the ability to decrease inflammation associated with tumors while simultaneously inducing cell death in cancer cells. Clarifying their mechanisms, guaranteeing stability, and enhancing effective delivery techniques for clinical usage should be the focus of future studies.

Intrinsic and extrinsic modulators of human dental pulp stem cells: advancing strategies for tissue engineering applications.

This review focuses on dental pulp stem cells (DPSCs) which are mesenchymal stem cells (MSCs) and originating from the neural crest. These cells possess a high capacity for self-renewal and multilineage differentiation. Because of these traits, they represent promising sources for tissue engineering, regenerative medicine, and clinical applications. The objective of this study was to assess the extrinsic and intrinsic factors influencing DPSC characteristics and their potential in tissue engineering. This review discusses the external and internal factors affecting DPSC properties, including proliferation, migration, differentiation, and gene expression post extraction. Additionally, it explores the impact of the microenvironment-its composition and physical properties-and genetic and epigenetic regulation on DPSC behavior. Variations in the microenvironment and genetic regulation play pivotal roles in modulating DPSC functions, including their proliferation and differentiation potential. Intrinsic and extrinsic factors are key barriers to realizing the full therapeutic potential of DPSCs. A deeper understanding of the extrinsic and intrinsic factors affecting DPSC behavior is critical for optimizing their use in regenerative medicine, particularly for dental and craniofacial applications. Although DPSCs hold significant promise, challenges remain, and this review provides insights into the current limitations and future directions for DPSC-based therapies. Researchers and clinicians are offered a comprehensive resource for advancing the field.

Harnessing Theraoenergetics for Cartilage Regeneration: Development of a Therapeutic and Bioenergetic Loaded Janus Nanofiber Reinforced Hydrogel Composite for Cartilage Regeneration.

Advancements in tissue engineering and regenerative medicine have highlighted different strategies of engineering and designing hydrogels to replicate the intricate structure of cartilage extracellular matrix (ECM) for effective cartilage regeneration. However, despite efforts to meet the elevated structural and mechanical demands of cartilage repair, researchers often overlook the challenging environmental conditions at damaged cartilage sites such as inflammation, hypoxia, and the limited availability of nutrients and energy, which are critical for supporting tissue regeneration. The insufficient oxygen, nutrient availability, and oxidative stress in avascular cartilage limit the oxidative phosphorylation-mediated bioenergetics in cells needed for energy demands required for anabolic biosynthesis, cell division, and migration during tissue repair. Thus, there is a need to develop an advanced approach to engineer a unique hydrogel system that not only provides intricate structural properties but also integrates therapeutics (like anti-inflammatory, reactive oxygen species (ROS) scavenging) and bioenergetics (like oxygen, energy demand) into the hydrogel, which may offer a holistic and effective solution for repairing cartilage defects under a harsh microenvironment. In this study, we engineered an innovative approach to develop a new class of theraoenergetic hydrogel system by reinforcing a Janus nanofiber (JNF) carrying therapeutic (MgO) and bioenergetic (polyglutamic acid), PGA) components into a dual network photo-crosslinkable hydrogel. Reinforcement of JNF microfragments and the photo-crosslinking dual network of synthesized gelatin methacryloyl (GelMA) and carboxymethyl chitosan (CMCh) not only enhances the hydrogel's mechanical properties by 800% to withstand mechanical load but also ensures a controlled release of magnesium, oxygen, and PGA over 30 days. Co-delivery of magnesium and bioenergetic PGA with oxygen helped synergistically to reduce intracellular ROS and inflammatory markers IL-6 and TNF-α, providing a supportive environment for enhancing cell mitochondrial oxidative metabolism leading to active proliferation and chondrogenic differentiation of stem cells to deposit glycosaminoglycan (GAG)-rich extracellular matrix to regenerate cartilage. The developed theraoenergetic hydrogel system represents a promising solution for regenerating cartilage under a harsh microenvironment to treat osteoarthritis, a rising global health burden.

Correlation in Stem Cell Technology, Tissue Engineering, and Regenerative Medicine

Correlation in Stem Cell Technology, Tissue Engineering, and Regenerative Medicine

Development and Characterization of Magnetic Nanoemulsion-Based Senolytic Peptides for Osteoarthritis Treatment

The formulation and characterization of a novel nanoemulsion (NE) delivery system for senomodulator peptides aimed at enhancing the treatment of osteoarthritis (OA) are reported, in combination with magnetic nanoparticles (MNPs), for improving targeted delivery and traceability. Osteoarthritis, a prevalent degenerative joint disease associated with aging, is currently not effectively treated by disease-modifying therapies, posing a consistent health burden on individuals and healthcare systems worldwide. Existing treatments, such as nonsteroidal anti-inflammatory drugs and intra-articular injections, are limited by inadequate local drug concentrations and rapid clearance, often necessitating costly joint replacement. Lipid-based NE composed of biocompatible and biodegradable vitamin E and sphingomyelin, associated with the senolytic peptide NE:TUB1, is able to target senescent cells implicated in OA progression. Improved cellular retention and therapeutic effects of the associated TUB1 peptide, compared to its free form, have been demonstrated, suggesting a significant enhancement in therapeutic potential. The incorporation of MNPs to obtain NE:TUB1-MNP formulations offers the advantage of being traceable in vivo through clinically available imaging technologies, with the potential to enhance targeting capabilities through magnetic guidance. The characterization of NE:TUB1-MNPs involved the assessment of their physical and chemical properties, interaction with cells, cytotoxicity profile, and nanoparticle uptake in vitro using human primary adipose-derived stem cells. NE and NE:TUB1-MNP are shown to be stable, non-toxic, and capable of efficient intracellular uptake. The inclusion of MNPs not only supports cell viability and proliferation but also facilitates medium and long-term product traceability within joints, offering a promising approach for localized treatment. The enhanced anti-senescent role of NE:TUB1-MNP formulations are highlighted, suggesting their potential utility in mitigating OA progression and possibly other degenerative diseases. In conclusion, the study presents a novel therapeutic approach for OA, NE:TUB1-MNPs, leveraging the synergistic effects of peptide-functionalized nanoemulsions and magnetic nanoparticles to improve targeted delivery and therapeutic outcomes. This innovative formulation could pave the way for new treatments for OA and other joint-related conditions, offering significant advancements in regenerative medicine.