Controlled Release Systems Research Articles

A biocompatible drug controlled release system based on β-cyclodextrin crosslinked magnetic lactose/ZIF-8 metal-organic frameworks for cancer treatment

Natural saccharides (Chitosan, Lactose, alginate, and β-cyclodextrin) have recently attracted much attention from researchers as drug delivery systems for cancer therapy. In this regard, for the first time, we designed a new targeted carrier based on magnetic lactose-modified ZIF-8 metal-organic frameworks crosslinked with β-cyclodextrin (M-Lactose@ZIF-8-β-CD) for the pH-responsive controlled release of anticancer drugs, hydrophilic doxorubicin (DOX), and hydrophobic curcumin (CUR) to MCF-7 breast cancer cells. The encapsulation efficiency of M-Lactose@ZIF-8-β-CD was found to be 95.16% for DOX and 65.01% for CUR. The in vitro release studies showed a pH-responsive controlled release of DOX and CUR from M-Lactose@ZIF-8-β-CD at pH 5, which confirmed the performance of the prepared carrier in the cancerous microenvironments. The release mechanism of both drugs was well described by the Korsmeyer-Peppas and Fickian diffusion. In addition, in vitro cytotoxicity, hemolysis, and antioxidant investigations clearly showed that the prepared M-Lactose@ZIF-8-β-CD carriers had good biocompatibility, high blood compatibility, and excellent antioxidant activity due to the presence of natural saccharides in carriers. Based on these findings, the M-Lactose@ZIF-8-β-CD can be applied as a promising targeted co-drug delivery carrier for cancer therapy.

Accelerated innervation of biofabricated skeletal muscle implants containing a neurotrophic factor delivery system

IntroductionVolumetric muscle loss (VML) is one of the most severe and debilitating conditions in orthopedic and regenerative medicine. Current treatment modalities often fail to restore the normal structure and function of the damaged skeletal muscle. Bioengineered tissue constructs using the patient’s own cells have emerged as a promising alternative treatment option, showing positive outcomes in fostering new muscle tissue formation. However, achieving timely and proper innervation of the implanted muscle constructs remains a significant challenge. In this study, we present a clinically relevant strategy aimed at enhancing and sustaining the natural regenerative response of peripheral nerves to accelerate the innervation of biofabricated skeletal muscle implants.MethodsWe previously developed a controlled-release neurotrophic factor delivery system using poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF). Here, we incorporate this neurotrophic factor delivery system into bioprinted muscle constructs to facilitate innervation in vivo.ResultsOur results demonstrate that the neurotrophic factors released from the microspheres provide a chemical cue, significantly enhancing the neurite sprouting and functional innervation of the muscle cells in the biofabricated muscle construct within 12 weeks post-implantation.DiscussionOur approach provides a clinically applicable treatment option for VML through accelerated innervation of biomanufactured muscle implants and subsequent improvements in functionality.

Medicinal cannabis delivery systems: A perspective

In recent years, cannabis derivatives have been proposed for the treatment of various medical conditions, including pain, inflammation, epilepsy, sleep disorders, multiple sclerosis, anorexia, schizophrenia, neurodegenerative diseases, nausea, and cancer. While the benefits of cannabis derivatives, primarily cannabinoids, have been demonstrated and continue to be studied, their use presents various challenges associated with their low water solubility, rapid metabolism, erratic and poor bioavailability, and erratic pharmacokinetics, which directly affect their efficacy. In this context, a great deal of research is being carried out to overcome these drawbacks by designing delivery systems capable of improving solubility/bioavailability, potency, and efficacy, while addressing the purity and quality issues required by the pharmaceutical industry. This article aims to critically review the major trends and challenges in designing controlled-release cannabinoid delivery systems and their potential application in the pharmaceutical industry.

Multilayer Nanocarrier for the Codelivery of Interferons: A Promising Strategy for Biocompatible and Long-Acting Antiviral Treatment

Background: Interferons (IFNs) are cytokines involved in the immune response with a synergistic regulatory effect on the immune response. They are therapeutics for various viral and proliferative conditions, with proven safety and efficacy. Their clinical application is challenging due to the molecules’ size, degradation, and pharmacokinetics. We are working on new drug delivery systems that provide adequate therapeutic concentrations for these cytokines and prolong their half-life in the circulation, such as nanoformulations. Methods: Through nanoencapsulation using electrospray technology and biocompatible and biodegradable polymers, we are developing a controlled release system based on nanoparticles for viral infections of the respiratory tract. Results: We developed a controlled release system for viral respiratory tract infections. A prototype nanoparticle with a core was created, which hydrolyzed the polyvinylpyrrolidone (PVP) shell , releasing the active ingredients interferon-alpha (IFN-α) and interferon-gamma (IFN-γ). The chitosan (QS) core degraded slowly, with a controlled release of IFN-α. The primary and rapid effect of the interferon combination ensured an antiviral and immunoregulatory response from day one, induced by IFN-α and enhanced by IFN-γ. The multilayer design demonstrated an optimal toxicity profile. Conclusions: This formulation is an inhaled dry powder intended for the non-invasive intranasal route. The product does not require a cold chain and has the potential for self-administration in the face of emerging viral infections. This novel drug has applications in multiple infectious, oncological, and autoimmune conditions, and further development is proposed for its therapeutic potential. This prototype would ensure greater bioavailability, controlled release, fewer adverse effects, and robust biological action through the simultaneous action of both molecules.

Studies of the Sorption-Desorption of Pesticides from Cellulose-Based Derivative Nanocomposite Hydrogels

This study analyzed the effect of cellulose derivatives, namely methylcellulose (MC) and carboxymethylcellulose (CMC), on the stability of zeolite in a polymeric solution that would synthesize a three-dimensional network of poly(methacrylic acid)-co-polyacrylamide (PMAA-co-PAAm). Additionally, it investigated the effect of pH on the release of paraquat (PQ) and difenzoquat (DFZ) herbicides. Similar to previous studies with hydrogels containing CMC, the presence of bi and trivalent salts, such as Ca+2 and Al+3, also drastically reduced their swelling degree from 6.7 g/g in NaCl (0.15 mol·L−1) to 2.1 g/g in an AlCl3 solution (0.15 mol·L−1) for the MC nanocomposite. The viscosity results may suggest that the formation of a polysaccharide-zeolite complex contributed to the zeolite stabilization. As for the adsorption results, all samples adsorbed practically the entire concentration of both herbicides in an aqueous solution. Finally, it was also observed that the valence of the salts and molecular weight of the herbicide affect the release process, where DFZ was the herbicide with the highest concentration released. Both nanostructured hydrogels with CMC and MC exhibited lower release at pH = 7.0. These results demonstrated that a more in-depth evaluation of the phenomena involved in the application of these materials in controlled-release systems could help mitigate the impact caused by pesticides.

Microfabrication of controlled release osmotic drug delivery systems assembled from designed elements

ABSTRACT Background This study investigates combining 3D printing with traditional compression methods to develop a multicomponent, controlled-release drug delivery system (DDS). The system uses osmotic tablet layers and a semipermeable membrane to control drug release, similar to modular Lego® structures. Methods The DDS comprises two directly compressed tablet layers (push and pull) and a semipermeable membrane, all contained within a 3D-printed frame. The membrane is made from cellulose acetate and plasticizers like glycerol and propylene glycol. Various characterization techniques, including Positron Annihilation Lifetime Spectroscopy (PALS), were employed to evaluate microstructural properties, wettability, morphology, and drug dissolution. Results Glycerol improved the membrane’s wettability, as confirmed by PALS. The system achieved zero-order drug release, unaffected by stirring rates, due to the push and pull tablets within the 3D-printed frame. The release profile was stable, demonstrating effective drug delivery control. Conclusion The study successfully developed a prototype for a controlled-release osmotic DDS, achieving zero-order release kinetics for quinine hydrochloride after 2 h. This modular approach holds potential for personalized therapies in human and veterinary medicine, allowing customization at the point of care.

New Intercalated Polymeric 2,4-Dichlorophenoxyacetic Acid Herbicide as Controlled Release Systems

New Intercalated Polymeric 2,4-Dichlorophenoxyacetic Acid Herbicide as Controlled Release Systems

Investigating the Feasibility of Xylitol and Gelatin for Controlled Release System in Drug Delivery using Calcium Alginate

Investigating the Feasibility of Xylitol and Gelatin for Controlled Release System in Drug Delivery using Calcium Alginate

Tailoring Fumaric Acid Delivery: The Role of Surfactant-Enhanced Solid Lipid Microparticles via Spray-Congealing.

Fumaric acid, a naturally occurring preservative with antimicrobial properties, has been widely used in the baking industry. However, its direct addition interferes with yeast activity and negatively impacts the gluten structure. This study investigates the potential of spray-congealing as a method for encapsulating fumaric acid within solid lipid microparticles. The selection of lipid carriers and surfactants is critical, so hydrogenated palm stearin, hydrogenated rapeseed oil, and Compritol ATO 888 (glyceryl behenate) were chosen as lipid carriers, and propylene glycol monostearate and glyceryl monolaurate were utilised as surfactants with varying concentrations. Rheological properties, encapsulation efficiency, particle size, moisture content, and thermal behaviour were assessed, along with the release profiles under different temperature conditions simulating the baking process. The findings indicate that the addition of surfactants significantly impacts the viscosity and stability of the molten mixtures, which in turn affects the spray-congealing process and the release of fumaric acid. The temperature-dependent and time-dependent release profiles demonstrate the potential for customising release kinetics to suit specific applications, such as the baking industry. This study may contribute to the development of a controlled-release system that synchronises with the baking process, thereby optimising fumaric acid's functionality while preserving the quality of baked goods.

How do various encapsulation techniques improve the oral delivery of food protein hydrolysates?

AbstractThe development of bioformulations based on food protein hydrolysates (FPHs) has gained significant traction in the food and pharmaceutical sectors due to their biophysical and biochemical properties, including health‐promoting effects, biocompatibility, and biodegradability. However, the oral delivery of FPHs presents notable technical challenges, largely due to their inherent limitations such as (bio)stability, permeability, bioavailability, and molecular size. This review provides a comprehensive overview of FPHs, including their structural characteristics, origins, methods of preparation, and associated health benefits. Additionally, it highlights the challenges related to their oral delivery. Recent advancements in the formulation and delivery of FPHs through biopolymeric controlled release systems—such as micro‐ and nanoparticles, hydrogels, biofunctional films and composites, and electrospun fibers—are discussed. We also explore lipid‐based delivery platforms, including liposomes, chitosomes, emulsions, Pickering emulsions, nanostructured lipid carriers, solid lipid nanoparticles, and surfactant‐based carriers. Furthermore, this article emphasizes the importance of controlled delivery and targeted release of FPHs following oral administration. The challenges in designing effective lipid/biopolymer‐based carriers for FPHs, along with future prospects and opportunities in this growing field, are also thoroughly examined.

Se-incorporated polycaprolactone spherical polyhedron enhanced vitamin B2 loading and prolonged release for potential application in proliferative skin disorders

Development of novel drug vehicles for vitamin B2 (VitB2) delivery is very important for designing controllable release system to improve epidermal growth and bone metabolism. In this work, selenium (Se)-incorporated polycaprolactone (PCL) spherical polyhedrons are successfully synthesized via a single emulsion solvent evaporation method which is utilized to load VitB2 to fabricate cell-responsive Se-PCL@VitB2 delivery systems. Their physicochemical properties are characterized by DLS, SEM, XRD, FTIR, and TGA-DSC. The release kinetics of VitB2 or Se from the samples are investigated in PBS solution (pH = 2.0, 5.0, 7.4, 8.0 and 12.0). The cytocompatibilities are also evaluated with normal BMSC and epidermal HaCat cells. Results exhibit that Se-PCL@VitB2 particles presents spherical polyhedral morphology (approximately (3.25 ± 0.46) μm), negative surface charge (-(54.03 ± 2.94) mV), reduced crystallinity and good degradability. Stability experiments imply that both VitB2 and Se might be uniformly dispersed in PCL matrix. And the incorporation of Se facilely promotes the loading of VitB2. The encapsulation efficiency and loading capacity are (98.42 ± 1.06)% and (76.25 ± 1.27) for Se-PCL@VitB2 sample. Importantly, it exhibits more prolonged release of both VitB2 and Se in neutral PBS solution (pH = 7.4) than other pH conditions. Presumably, the electrostatic interaction between Se, VitB2 and PCL contribute to its release mode. Cell experiments show that Se-PCL@VitB2 presents strong cytotoxicity to HaCat cells mainly due to the cytotoxic effect of Se anions and PCL degradation products. However, it exhibits weak inhibitory effect on BMSC cells. These note that the synthesized Se-PCL@VitB2 particles can be promising drug vehicles for potential application in epidermal proliferative disorders.

Preparation of ternary hybridized chitosan microspheres with photothermal effect for pH-sensitive long-lasting controlled release system and its release mechanism.

To enhance the effective utilization of drugs and diminish the number of medications for patients, it is vital to investigate controlled long-acting drug release systems and their release mechanisms. In this study, chitosan microspheres were synthesized by cross-linking pH-sensitive Schiff bases, and Zif-8, a pH-sensitive component, was encapsulated within them. Furthermore, MXene was incorporated as a third component to augment the strength and photothermal synergistic characteristics of the microspheres. By adjusting the ratio of each component, the optimal ternary heterogeneous functional pH-controllable long-lasting drug release system was obtained. The optimal coating and the most effective adsorption-release effect were achieved. The release mechanism was examined under varying pH and temperature conditions. The release process was found to be divided into three stages. The initial phase was predominantly governed by the Fick diffusion mechanism, whereas the subsequent phases were primarily regulated by the pH-induced co-decomposition of CS and Zif-8, and the individual decomposition of CS, respectively. The drug was observed to be released in a linear manner during the latter two stages of the experiment. This was evidenced by the persistent release of ciprofloxacin hydrochloride in response to pH changes, and further supported by the results of tests on its antimicrobial properties. The drug release persisted for over three days at pH5.4 and could be utilized repeatedly, exhibiting promising applications in drug delivery. Moreover, the drug's photothermal properties offer the possibility of developing synergistic therapeutic programs.

Comparative Study of Single and Coaxial Electrospun Antimicrobial Cross-Linked Scaffolds Enriched with Aloe Vera: Characterization, Antimicrobial Activity, Drug Delivery, Cytotoxicity, and Cell Proliferation on Adipose Stem Cells and Human Skin Fibroblast.

The preparation of materials with application in the biomedical field needs to attend some characteristics such as biocompatibility, nontoxicity, adequate mechanical properties, and the ability to mimic the extracellular matrix. Scaffolds for use in cell culture were prepared based on gelatin, polylactic acid (PLA), aloe vera mucilage, and tetracycline. Fibers were prepared in single and coaxial configuration and then cross-linked with glutaraldehyde saturated vapor. The fibers were obtained with cylindric morphology and changed to ribbon morphology and porous membranes, similarly to the extracellular matrix, when cross-linked. Membranes prepared by coaxial electrospinning showed core-shell structures when observed by transversal images, which is beneficial for controlled drug release. Characterization techniques such as scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy demonstrated the cross-linking due to the increase in diameter, formation of imine groups, and improvement of thermal stability. Antibiotic release tests showed that the prevalent release mechanism is diffusion and can be controlled considering the encapsulation effect, when fibers are prepared with a coaxial configuration, increasing the drug release time, making it a suitable material for controlled release. The biological evaluation of the scaffolds was carried out in two cell lines: mammalian adipose stem cells (ASCs), used as a primary cell culture, and Detroit 548 human skin fibroblasts as a dermal cell model. Aloe vera enriched scaffolds showed better activity in contact with both cell lines, exhibiting cell viability values greater than 90% and favorable results in live-dead assays when no damaged cells were observed. Cell proliferation was evaluated using Detroit 548 human skin fibroblast on gelatin-based scaffolds by the staining of the adhered cells; the images showed good confluence and morphology of the cells on the aloe vera and antibiotic loaded membranes for both of the studied configurations. Antibiotic loaded membranes presented antimicrobial activity against S. aureus, and this behavior increased when aloe vera is included. According to the results, the scaffolds prepared on single configuration enriched with aloe vera and tetracycline could be used in dermal tissue engineering as burn dressings, diabetic foot apposite, and skin substitutes, and the scaffolds prepared with a coaxial configuration are recommended for controlled release systems of antibiotics as treatments for chronic wounds such as diabetic foot and burn healing.

Clinical and Market Analysis of NanoBEO: A Public-Worth, Innovative Therapy for Behavioral and Psychological Symptoms of Dementia (BPSD)-Emerging Evidence and Its Implications for a Health Technology Assessment (HTA) and Decision-Making in National Health Systems.

According to scientific literature, some 99% of patients affected by Alzheimer's disease (AD) suffer from behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms (NPSs). In particular, agitation is one of the most difficult disorders to treat. States of agitation represent a very serious problem as they make these subjects dangerous for themselves and others and worsen as the disease advances. To date, there are no specific solutions for treating agitation. The only authorized drug is risperidone (as well as brexpiprazole, approved by the FDA on 11 May 2023), which can be used for no longer than 6-12 weeks because it increases the risk of death-owing to cardiocerebrovascular accidents-by 1.6-1.7 times. In order to address the latter noteworthy unmet medical need, NanoBEO was produced. The aim of the present work is to generate the health technology assessment (HTA) of this nanotechnological device. The latter consists of a controlled release system, based on solid lipid nanoparticles loaded with bergamot essential oil (BEO). The results of the present research assessed the current evidence in the field of non-pharmacological treatments for this condition, including relevant primary preclinical and clinical data studies supporting the use of this device and the production of the operative plan for its launch on the market. The findings offer recommendations for decision-making on its implementation in dementia. NanoBEO represents a public-worth innovation in this neglected area, marking a significant advancement in the history of dementia, moving from academic research to product development.

Controlled release of atrazine from a polyurethane matrix for improved agricultural use

This study investigated the controlled release kinetics of the herbicide atrazine (ATZ) from a polyurethane (PU) matrix. To address the environmental concerns associated with the widespread use of atrazine, particularly its high mobility due to low adsorption and stability, this research evaluated the potential of PU as a matrix for a controlled release system (CRS). The PU/ATZ film was fabricated via the casting method and characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and Fourier transform infrared spectroscopy (FTIR). In vitro release tests were performed to assess the atrazine release profile, employing mathematical models, including Korsmeyer-Peppas and Higuchi, to elucidate the release mechanisms. The findings demonstrated that the PU matrix effectively facilitated controlled release, with approximately 30% of atrazine released over 96 h. The Korsmeyer‒Peppas model yielded the best fit for the release kinetics, indicating that the release mechanism follows Fickian diffusion.

Impact of Drug Delivery Systems on Radiological Imaging Quality; A Comparative Analysis Through Systematic Review

Background: Smart, or controlled release systems are one of the major developments in pharmacology which has the potential of improving the efficacy of a drug while reducing the toxic impact it has on the rest of the body. These systems include all the nano-technological strategies and controlled release strategies targeted at delivering drugs to the tissues. Aim: Verify and quantify the effects of different drug delivery systems throughout the quality of radiological imaging. Thus, the study aims to determine the most useful strategies referring to the improvement of the contrast, Method: From PubMed, Scopus, and Web of Science databases starting from 2019 to 2024, an electronic search yielded 6858 articles, out of which only relevant English articles were considered. The search criteria included articles and reviews concerning advanced drug delivery system, while exclusion factors were low methodological quality of the studies and articles published in languages other than English. In total, 8 papers were identified that met the criteria for further qualitative analysis, which creates a reasonable and strong foundation for the synthesis of the developments in question. Results: Evidently, progressive nanocarriers and SDDS were established to improve significantly the quality of radiological imaging over conventional DDS. Liposomes, micelles, and quantum dots, which are examples of nanocarriers, as well as SDDS, exhibited enhanced targeting precision, increased bioavailability, and enhanced contrast in imaging. However, the following drawbacks were highlighted: Toxicity of the materials, biocompatibility problems, and high costs of fabrication. Conclusion: The current reviewed works are revealing major progresses in the drug delivery systems such as liposomes, micelles and quantum dots nanocarriers employed for the targeted and stimuli-responsive delivery of the drug molecules. Some of the key findings pointed towards the effectiveness of such microsystems in increasing drug solubility and bioavailability, reducing systemic toxicity and in overhauling therapeutic outcomes in cancer treatment and other health applications.

Prolonging Cyclamen Flower Vase Life via 8-HQS and AgNO3 Treatments in a Controlled Release System

The current study applied electrospun fibers containing 8-hydroxyquinoline-5-sulfonic acid (8-HQS) (100, 150, and 200 mg L−1) and silver nitrate (AgNO3) (15 and 20 mg L−1) to enhance the longevity and qualitative parameters of two cyclamen cultivars. The results indicated that the vase life of the flowers treated with 20 mg L−1 AgNO3 and 200 mg L−1 8-HQS was higher than that of the other treatments (16 days). Cyclamens treated with 8-HQS (100 mg L−1) + AgNO3 (15 mg L−1) and 8-HQS (100 mg L−1) + AgNO3 (20 mg L−1) had lower polyphenol oxidase (PPO) activity than the control group. Also, it was observed that the higher phenylalanine ammonia-lyase (PAL) enzyme activity of cyclamens in the 8-HQS (150 mg L−1) + AgNO3 (15 mg L−1) treatment was longer than that of the other treatments and control groups. Treatment with 100 mg L−1 8-HQS and 20 mg L−1 AgNO3 showed higher peroxidase (POD) activity than the different treatments. This research indicated that adding AgNO3 and 8-HQS to electrospun fibers is a promising method for enhancing the longevity and maintaining the quality of these cut flowers.

Effect of inulin on structural, physicochemical, and in vitro gastrointestinal tract release properties of core-shell hydrogel beads as a delivery system for vitamin B12

In this study, core-shell hydrogel beads were developed as a controlled-release delivery system for vitamin B12. Vitamin B12-loaded microgels (MG) were prepared using gellan gum (GG). Core-shell hydrogel beads were produced by incorporating MG into pea protein isolate (PPI) and sodium alginate (AL) matrix filled/coated with different concentrations (0 %, 1 %, 3 %, 5 %, and 10 %) of inulin (IN). Based on XRD analysis, MG was successfully incorporated into core-shell hydrogel beads. In FE-SEM and FT-IR analyses, the smoother surface and denser structure of the beads were observed as IN concentration increased due to hydrogen bonds between IN and the beads. The encapsulation efficiency increased from 68.64 % to 82.36 % as IN concentration increased from 0 % to 10 %, respectively. After exposure to simulated oral and gastric conditions, core-shell hydrogel beads exhibited a lower cumulative release than MG, and a more sustained release was observed as IN concentration increased in simulated intestinal conditions.

Recent Advances in Biopesticide Formulations for Targeted Insect Pest Management: A Review

The increasing environmental and health concerns associated with the use of synthetic chemical pesticides have driven the need for alternative, eco-friendly pest management solutions. Biopesticides, derived from natural sources such as plants and microorganisms, offer a promising solution, as they are less toxic, decompose quickly, and target specific pests with minimal impact on non-target organisms. Recent advancements in biopesticide formulations, including nano pesticides, controlled release formulations (CRFs), hydrogels, polymer-coated granules, and tablets, are enhancing the effectiveness, stability, and environmental safety of these products. The integration of nanotechnology and controlled release systems in biopesticides is opening new avenues for sustainable agriculture. This review discusses the various biopesticide formulation technologies, highlighting their advantages, disadvantages, and future prospects.

Leveraging the Physicochemical Attributes of Biomimetic Hydrogel Nanocomposites in Stem Cell Differentiation.

The field of tissue engineering has witnessed significant advancements with the advent of hydrogel nanocomposites (HNC), emerging as a highly promising platform for regenerative medicine. HNCs provide a versatile platform that significantly enhances the differentiation of stem cells into specific cell lineages, making them highly suitable for tissue engineering applications. By incorporating nanoparticles, the mechanical properties of hydrogels, such as elasticity, porosity, and stiffness, are improved, addressing common challenges such as short-term stability, cytotoxicity, and scalability. These nanocomposites also exhibit enhanced biocompatibility and bioavailability, which are crucial to their effectiveness in clinical applications. Furthermore, HNCs are responsive to various triggers, allowing for precise control over their chemical properties, which is beneficial in creating 3D microenvironments, promoting wound healing, and enabling controlled drug delivery systems. This review provides a comprehensive overview of the production methods of HNCs and the factors influencing their physicochemical and biological properties, particularly in relation to stem cell differentiation and tissue repair. Additionally, it discusses the challenges in developing HNCs and highlights their potential to transform the field of regenerative medicine through improved mechanotransduction and controlled release systems.