Injectable Gel Research Articles

Enhancing intrinsic TGF-β signaling via heparan sulfate glycosaminoglycan regulation to promote mesenchymal stem cell capabilities and chondrogenesis for cartilage repair

Osteoarthritis burdens patients due to the limited regenerative capacity of chondrocytes. Traditional cartilage repair often falls short, necessitating innovative approaches. Mesenchymal stem cells (MSCs) show promise for regeneration. Heparan sulfate glycosaminoglycans (HS-GAGs) regulate cellular functions, making them a target for cartilage repair. This study highlights how Heparinase III (HepIII) cleaves intact HS-GAGs in bone marrow-derived MSCs (BM-MSCs), enhancing their capabilities and specifically promoting chondrogenesis. HepIII-treated BM-MSCs cultured in a hanging drop device for three days, significantly increased cell number and aggregation into a cell sphere with early chondrogenesis. HepIII promoted BM-MSCs toward chondrogenesis, increasing type II collagen, intact HS-GAGs, and sulfated GAG content, while upregulating chondrogenic and heparan sulfate proteoglycan genes. Treatment with the TGF-β inhibitor (SB-431542) in HepIII-treated BM-MSCs demonstrated enhanced intrinsic transforming growth factor-β (TGF-β) signaling and fibronectin expression. This approach also boosted BM-MSC self-renewal, immunosuppressive potential, and modified acetylated histone signatures, offering a cost-effective strategy for cartilage repair by addressing inflammation, metabolic changes, and the high costs of traditional TGF-β methods. From the results, HepIII-treated BM-MSCs show potential for use in combination with other biopolymers as injectable gels to improve cartilage repair in osteoarthritis patients in the near future.

Platelet-rich fibrin in the management of oral mucosal lesions: a scoping review

ObjectivesOral mucosal lesions are prevalent and often cause pain, thus impacting patients' quality of life. Platelet-rich fibrin (PRF) has emerged as a promising autologous biomaterial for wound healing, yet comprehensive evidence regarding its efficacy in treating oral mucosal lesions is limited. This study aims to update the current evidence on the effectiveness of PRF in treating various types of oral mucosal lesions.Materials and methodsWe conducted a literature search in PubMed, Scopus, Embase, and Web of Science databases until April 2024. The search included studies that investigated the use of PRF in treating oral mucosal lesions. Twelve studies met the inclusion criteria, comprising three case reports, three randomized controlled trials, two animal studies, three split-mouth trials, and one retrospective study. We performed data extraction according to a predefined form.ResultsPRF was applied in two forms—membranes and injectable gels—to treat a range of oral mucosal lesions, including ulcerative, red and white, pigmented, and potentially malignant or malignant lesions. Compared to control groups or conventional treatments, PRF generally demonstrated superior outcomes regarding faster healing, lesion size reduction, symptom relief, and lower recurrence rates. Histological and molecular analyses from some studies also indicated PRF's regenerative and anti-inflammatory effects.ConclusionPRF shows promise as an effective and safe alternative to current treatments for oral mucosal lesions due to its autologous nature, ease of preparation, and wound-healing capabilities. However, further research is needed to standardize PRF preparation protocols and confirm its long-term efficacy across different lesion types.

Minimally Invasive Injectable Gel for Local Immunotherapy of Liver and Gastric Cancer.

Local immunotherapy represents a promising solution for preventing tumor recurrence and metastasis post tumor surgical resection by eliminating residue tumor cells as well as eliciting tumor-specific immune responses. Minimally invasive surgery has become a mainstream surgical method worldwide due to its advantages of aesthetics and rapid postoperative recovery. Unfortunately, the currently reported local immunotherapy strategies are mostly designed to be used after open laparotomy, which go against the current surgical philosophy of minimally invasive therapy and is not suitable for clinical translation. Aiming at this problem, a minimally invasive injectable gel (MIGel) is herein reported loaded with immunotherapeutic agents for gastric and liver cancer postoperative treatment. The MIGel is formed by crosslinking between oxidized dextran (ODEX) and 4-arm polyethylene glycol hydroxylamine (4-arm PEG-ONH2) through oxime bonds, which can be injected through a clinic-used minimally invasive drainage tube and adhered tightly to the tissue. The loaded oxaliplatin (OxP) and resiquimod (R848) can be released constantly over two weeks and resulted in over 75% cure rate in orthotopic mouse gastric and liver cancer model. Collectively, a concept of minimally invasive local immunotherapy is proposed and MIGel is designed for local intraperitoneal cancer immunotherapy through minimally invasive surgery, with good clinical translation potential.

Supramolecular Enzyme-Peptide Gels for Localized Therapeutic Biocatalysis.

Enzyme therapeutics are often compromised by poor accumulation within target tissues, necessitating high doses that can exacerbate off-target effects. We report an injectable supramolecular enzyme-peptide gel platform for prolonged local enzyme retention in vivo . The gel is based on CATCH(+/-) ( C o- A ssembling T ags based on CH arge-complementarity), cationic and anionic peptide pairs that form β-sheet fibrils upon mixing 1 . Enzymes recombinantly fused to CATCH(-) peptide integrate into CATCH(+/-) β-sheet fibrils during assembly, resulting in an enzyme-peptide gel. Catalytically-active gels were fabricated with four disparate enzymes: CATCH(-)-NanoLuc luciferase, CATCH(-)-cutinase, CATCH(-)-uricase, and CATCH(-)-adenosine synthase A. CATCH(-)-cutinase gels demonstrated tunability of the platform, while CATCH(-)-NanoLuc gels demonstrated prolonged tissue retention relative to soluble enzyme. CATCH(-)-uricase gels resolved localized inflammation in a gout model, while CATCH(-)-adenosine synthase A gels suppressed localized lipopolysaccharide-induced inflammation. Modular and tunable enzyme content, coupled with prolonged tissue retention, establish CATCH enzyme-peptide gels as a generalizable vehicle for effective local therapeutic biocatalysis.

Shear-thinning hydrogel for allograft cell transplantation and externally controlled transgene expression

This work establishes the design of a fully synthetic, shear-thinning hydrogel platform that is injectable and can isolate engineered, allogeneic cell therapies from the host. We utilized RAFT to generate a library of linear random copolymers of N,N-dimethylacrylamide (DMA) and 2-vinyl-4,4-dimethyl azlactone (VDMA) with variable mol% VDMA and degree of polymerization. Poly(DMA-co-VDMA) copolymers were subsequently modified with either adamantane (Ad) or β-cyclodextrin (Cd) through amine-reactive VDMA to prepare hydrogel precursor macromers containing complementary guest-host pairing pendant groups that, when mixed, form shear-thinning hydrogels. Rheometric evaluation of the hydrogel library enabled identification of lead macromer structures comprising 15 mol% pendants (Ad or Cd) and a degree of polymerization of 1000; mixing of these Ad and Cd functionalized precursors yielded hydrogels possessing storage modulus above 1000 Pa, tan(δ) values below 1 and high yield strain, which are target characteristics of robust but injectable shear-thinning gels. This modular system proved amenable to nanoparticle integration with surface-modified nanoparticles displaying Ad. The addition of the Ad-functionalized nanoparticles simultaneously improved mechanical properties of the hydrogels and enabled extended hydrogel retention of a model small molecule in vivo. In studies benchmarking against alginate, a material traditionally used for cell encapsulation, the lead hydrogel showed significantly less fibrous encapsulation in a subcutaneous implant site. Finally, this platform was utilized to encapsulate and extend in vivo longevity of inducible transgene-engineered mesenchymal stem cells in an allogeneic transplant model. The hydrogels remained intact and blocked infiltration by host cells, consequently extending the longevity of grafted cell function relative to a benchmark, shear-thinning hyaluronic acid-based gel. In sum, the new synthetic, shear-thinning hydrogel system presented here shows potential for further development as an injectable platform for delivery and in situ drug modulation of allograft and engineered cell therapies.

Bioactive Glial-Derived Neurotrophic Factor from a Safe Injectable Collagen-Alginate Composite Gel Rescues Retinal Photoreceptors from Retinal Degeneration in Rabbits.

The management of vision-threatening retinal diseases remains challenging due to the lack of an effective drug delivery system. Encapsulated cell therapy (ECT) offers a promising approach for the continuous delivery of therapeutic agents without the need for immunosuppressants. In this context, an injectable and terminable collagen-alginate composite (CAC) ECT gel, designed with a Tet-on pro-caspase-8 system, was developed as a safe intraocular drug delivery platform for the sustained release of glial-cell-line-derived neurotrophic factor (GDNF) to treat retinal degenerative diseases. This study examined the potential clinical application of the CAC ECT gel, focusing on its safety, performance, and termination through doxycycline (Dox) administration in the eyes of healthy New Zealand White rabbits, as well as its therapeutic efficacy in rabbits with sodium-iodate (SI)-induced retinal degeneration. The findings indicated that the CAC ECT gel can be safely implanted without harming the retina or lens, displaying resistance to degradation, facilitating cell attachment, and secreting bioactive GDNF. Furthermore, the GDNF levels could be modulated by the number of implants. Moreover, Dox administration was effective in terminating gel function without causing retinal damage. Notably, rabbits with retinal degeneration treated with the gels exhibited significant functional recovery in both a-wave and b-wave amplitudes and showed remarkable efficacy in reducing photoreceptor apoptosis. Given its biocompatibility, mechanical stability, controlled drug release, terminability, and therapeutic effectiveness, our CAC ECT gel presents a promising therapeutic strategy for various retinal diseases in a clinical setting, eliminating the need for immunosuppressants.

Transforming Cell-Drug Interaction through Granular Hydrogel-Mediated Delivery of Polyplex Nanoparticles for Enhanced Safety and Extended Efficacy in Gene Therapy.

The utilization of hydrogels for DNA/cationic polymer polyplex nanoparticle (polyplex) delivery has significantly advanced gene therapy in tissue regeneration and cancer treatment. However, persistent challenges related to the efficacy and safety of encapsulated polyplexes, stemming from issues such as aggregation, degradation, or difficulties in controlled release during or postintegration with hydrogel scaffolds, necessitate further exploration. Here, we introduce an injectable gene therapy gel achieved by incorporating concentrated polyplexes onto densely packed hydrogel microparticles (HMPs). Polyplexes, when uniformly adhered to the gene therapy gel through reversible electrostatic interactions, can detach from the HMP surface in a controlled manner, contrasting with free polyplexes, and thereby reducing dose-dependent toxicity during transfection. Additionally, the integration of RGD cell adhesion peptides enhances the scaffolding characteristics of the gel, facilitating cell adhesion, migration, and further minimizing toxicity during gene drug administration. Notably, despite the overall transfection efficiency showing average performance, utilizing confocal microscopy to meticulously observe and analyze the cellular states infiltrating into various depths of the gene therapy gel resulted in the groundbreaking discovery of significantly enhanced local transfection efficiency, with primary cell transfection approaching 80%. This phenomenon could be potentially attributed to the granular hydrogel-mediated delivery of polyplex nanoparticles, which revolutionizes the spatial and temporal distribution and thus the "encounter" mode between polyplexes and cells. Moreover, the gene therapy gel's intrinsic injectability and self-healing properties offer ease of administration, making it a highly promising candidate as a novel gene transfection gel dressing with significant potential across various fields, including regenerative medicine and innovative living materials.

Comparative analysis of in vivo bio-integration of three hyaluronic acid-based fillers for 26 weeks: a histological study

ABSTRACT Stabilized hyaluronic acid (HA), produced through diverse cross-linking technology and formulated as an injectable gel, has found widespread utilization in aesthetic industry. Cross-linked HA essentially constitutes a gel particle composition formed by numerous viscoelastic particulates. Various product formulations yield HA gels with distinct properties, including particle size, viscoelasticity, and interaction forces between particles. While previous studies have primarily concentrated on the biological safety and macroscopic expression of fillers, limited research exists on the internal mechanisms governing their macro-performance. This study selected three common dermal fillers for analysis, establishing an animal model to assess their in vivo interaction with surrounding tissues and explore their internal mechanisms. The findings revealed that particle size plays a crucial role in tissue integration.

Coordinating Macrophage Targeting and Antioxidation by Injectable Nanocomposite Hydrogel for Enhanced Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA), an immune-mediated inflammatory disease, is characterized by a large number of infiltrated immune cells and abnormally elevated reactive oxygen species (ROS) in the joint. Various proinflammatory factors secreted by macrophages and the elevated ROS by inflammatory cells are deeply intertwined and together contribute to joint damage. Targeted and sustained anti-inflammation and antioxidation strategies are needed for RA treatment. To alleviate the oxidative stress and target the source of inflammatory cytokines, we developed a thermosensitive injectable hydrogel, Dex-DSLip/Cro@Gel, to coordinate the targeted anti-inflammatory and antioxidation effects. Within the injectable gel, dexamethasone (Dex)-loaded liposomes (Dex-DSLip), modified with dextran sulfate (DS), target macrophages via interaction with scavenger receptor A (SR-A). Simultaneously, crocin I (Cro) is loaded in the gel with a high loading capacity. The porous structure of Dex-DSLip/Cro@Gel successfully prolongs the retention time of both drugs and sustains the release of Dex and Cro. After intra-articular injection of Dex-DSLip/Cro@Gel in RA rats, the expression of inflammatory factors in the ankle joints was significantly reduced. Joint erythema and bone erosion were markedly alleviated. Through the synergistic effects of Dex and Cro, Dex-DSLip/Cro@Gel demonstrates targeted anti-inflammatory and antioxidation effects as well as mitigated bone erosion and long-term therapeutic effects for RA. This thermosensitive injectable nanocomposite hydrogel synergizes anti-inflammatory and antioxidation effects and targets the microenvironment in the joint, offering a new approach for RA treatment.

Safe and Effective Restoration of Jawline Definition With Hyaluronic Acid Injectable Gel VYC-25L: Results From a Randomized Controlled Study.

A well-defined jawline improves overall facial aesthetics, thus motivating patients to seek jawline augmentation. This study will evaluate the safety and effectiveness of the hyaluronic acid injectable gel VYC-25L for restoring jawline definition. A US multicenter, evaluator-blinded study randomized adults with grade 2 (moderate) or 3 (severe) Allergan Loss of Jawline Definition Scale (ALJDS) scores. Participants were randomized to VYC-25L treatment group or control group at study onset, with 12 months follow-up. The control group had the option to receive treatment after 6 months (primary endpoint completion). Effectiveness measures included month 6 ALJDS responders rate (proportion of participants with ≥1-grade improvement from baseline on both sides), FACE-Q Satisfaction With Lower Face and Jawline scores, and Global Aesthetic Improvement Scale (GAIS) responders (improved/much improved) as assessed by the investigator and participants. Injection site responses (ISRs) and adverse events (AEs) were monitored. At month 6, ALJDS responder rates were 69.0% versus 38.0% in the VYC-25L treatment (n = 157) and control (n = 49) groups, respectively (p = .0001). In the VYC-25L treatment group, FACE-Q scores improved by a mean of 45.9 points versus baseline at month 6 (p < .0001). Furthermore, 88.4% and 89.0% of participants in the VYC-25L treatment group were GAIS responders on month 6 by participant- and investigator-assessment, respectively. Most ISRs were mild or moderate and resolved within 2 weeks. Most treatment-related AEs were mild and resolved within a week. VYC-25L safely and effectively restores jawline definition through 1 year.

Injectable Biomimetic Gels for Biomedical Applications.

Biomimetic gels are synthetic materials designed to mimic the properties and functions of natural biological systems, such as tissues and cellular environments. This manuscript explores the advancements and future directions of injectable biomimetic gels in biomedical applications and highlights the significant potential of hydrogels in wound healing, tissue regeneration, and controlled drug delivery due to their enhanced biocompatibility, multifunctionality, and mechanical properties. Despite these advancements, challenges such as mechanical resilience, controlled degradation rates, and scalable manufacturing remain. This manuscript discusses ongoing research to optimize these properties, develop cost-effective production techniques, and integrate emerging technologies like 3D bioprinting and nanotechnology. Addressing these challenges through collaborative efforts is essential for unlocking the full potential of injectable biomimetic gels in tissue engineering and regenerative medicine.

Injectable Thermosensitive Gel CH-BPNs-NBP for Effective Periodontitis Treatment through ROS-Scavenging and Jaw Vascular Unit Protection.

Periodontitis, a prevalent inflammatory condition in the oral cavity, is closely associated with oxidative stress-induced tissue damage mediated by excessive reactive oxygen species (ROS) production. The jaw vascular unit (JVU), encompassing both vascular and lymphatic vessels, plays a crucial role in maintaining tissue fluid homeostasis and contributes to the pathological process in inflammatory diseases of the jaw. This study presents a novel approach for treating periodontitis through the development of an injectable thermosensitive gel (CH-BPNs-NBP). The gel formulation incorporates black phosphorus nanosheets (BPNs), which are notable for their ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator that promotes lymphatic vessel function within the JVU. These results demonstrate that the designed thermosensitive gel serve as a controlled release system, delivering BPNs and NBP to the site of inflammation. CH-BPNs-NBP not only protects macrophages and human lymphatic endothelial cells from ROS attack but also promotes M2 polarization and lymphatic function. In in vivo studies, this work observes a significant reduction in inflammation and tissue damage, accompanied by a notable promotion of alveolar bone regeneration. This research introduces a promising therapeutic strategy for periodontitis, leveraging the unique properties of BPNs and NBP within an injectable thermosensitive gel.

Cu–Tremella fuciformis polysaccharide–based tumor microenvironment–responsive injectable gels for cuproptosis-based synergistic osteosarcoma therapy

Cuproptosis affects osteosarcoma locally, and the exploitation of cuproptosis-related biomaterials for osteosarcoma treatment is still in its infancy. We designed and synthesized a novel injectable gel of Cu ion–coordinated Tremella fuciformis polysaccharide (TFP–Cu) for antiosteosarcoma therapy. This material has antitumor effects, the ability to stimulate immunity and promote bone formation, and a controlled Cu2+ release profile in smart response to tumor microenvironment stimulation. TFP–Cu can selectively inhibit the proliferation of K7M2 tumor cells by arresting the cell cycle and promoting cell apoptosis and cuproptosis. TFP–Cu also promoted the M1 polarization of RAW264.7 cells and regulated the immune microenvironment. These effects increased osteogenic gene and protein expression in MC3T3-E1 cells. TFP–Cu could significantly limit tumor growth in tumor-bearing mice by inducing tumor cell apoptosis and improving the activation of anti-CD8 T cell-mediated immune responses. Therefore, TFP–Cu could be a potential candidate for treating osteosarcoma and bioactive drug carrier for further cancer-related applications.

Impact of Injection-Based Delivery Parameters on Local Distribution Volume of Ethyl-Cellulose Ethanol Gel in Tissue and Tissue Mimicking Phantoms.

Local drug delivery aims to minimize systemic toxicity by preventing off-target effects; however, injection parameters influencing depot formation of injectable gels have yet to be thoroughly studied. We explored the effects of needle characteristics, injection depth, rate, volume, and polymer concentration on gel ethanol distribution in both tissue and phantoms. The polymer ethyl cellulose (EC) was added to ethanol to form an injectable gel to ablate cervical precancer and cancer. Tissue mimicking phantoms composed of 1% agarose dissolved in deionized water were used to establish overall trends between various injection parameters and the resulting gel distribution. Additional experiments were performed in excised swine cervices with a CT-imageable injectate formulation, which enabled visualization of the distribution without tissue sectioning. Needle type and injection rate had minimal impact on gel distribution, while needle depths ≥13 mm yielded significantly larger distributions. Needle gauge and EC concentration impacted injection pressure with maximum gel distribution achieved when the pressure was 70-250 kPa. Injection volumes ≤3 mL of 6% EC-ethanol minimized fluid leakage away from the injection site. Results guided the development of a speculum-compatible hand-held injector to deliver gel ethanol into the cervix. Needle depth, gauge, and polymer concentration are critical to consider when delivering injectable gels. This study addressed key questions related to the impact of injection-based parameters on gel distribution at a scale relevant to human applications including: 1) how best to deliver EC-ethanol into the cervix and 2) general insights about injection protocols relevant to the delivery of injectable gels in tissue.

Carboxymethyl chitosan and dialdehyde cellulose nanocrystal based injectable self-healing emulsion gel

The study aims to demonstrate a general method for producing emulsion gels with self-healing properties. Specifically, the self-healing emulsion gels were fabricated by crosslinking carboxymethyl chitosan (CMC) stabilized emulsion with dialdehyde cellulose nanocrystal (DACNC). The reversible imine bonds between primary amino groups from CMC and aldehyde groups from DACNC endow the emulsion gel with self-healing properties. The compressive strength of the emulsion gels was greatly increased from 37.43 kPa 83.7 kPa by encapsulating emulsion droplets (φ = 0 %–40 %.) in the gel matrix. Moreover, the emulsion gels exhibited much better self-healing and injectability ability compared to hydrogel because the emulsion droplets interacted with the 3D gel matrix, which were observed by cryo-SEM and CLSM. The emulsion droplets distributed in the gel matrix improved the mobility and interfacial contact area of CMC and DACNC. Water contact measurement confirmed that the CMC/DACNC self-healing emulsion gels showed a hydrophilic surface. The CMC/DACNC emulsion gels could maintain a good structural stability as the oil loss was <1 % after centrifugation. This research provides a method to keep the structural stability of emulsion gels by inducing self-healing ability and modified cellulose nanocrystals, which could extend the shelf life and application area of emulsion gels.

An injectable antibacterial hydrogel with bacterial-targeting properties for subcutaneous suppuration treatment

Purulent infections present challenges to medical procedures and burden patients with drainage procedures. An injectable antibacterial hydrogel can be directly administered to the infected tissue through a syringe, making it one of the most effective strategies for treating subcutaneous infections. In this study, we utilized an injectable hydrogel (PHP gel) with targeted bactericidal properties for surgery-free treatment of subcutaneous infections. The PHP gel was cross-linked using the Schiff base reaction between amino-functionalized polyhydromethylpyrimidine (PHP-NH2) and oxidized dextran (o-Dex). PHP-NH2 possesses the ability to kill bacteria through electrostatic interactions, while o-Dex enhances bacterial targeting by binding to lectins on the bacterial outer membrane via sugar units. In vitro experiments demonstrated that the PHP gel effectively eradicated 100 % of pathogenic bacteria within 2 h. Moreover, when used in vivo for treating purulent subcutaneous infections, the injectable PHP gel exhibited remarkable efficacy by preventing infection progression and eliminating pustule tissue within 24 h. Importantly, no significant adverse effects on blood or organ systems were observed in mice treated with PHP gel. Therefore, this polysaccharide- and polyhydropyrimidine- based hydrogel material holds immense potential as a novel antibacterial agent for managing purulent subcutaneous infections.

Evaluation of the Filling Effects and Safety of an Injectable Gel Based on A Multi-Crosslinked Hyaluronan (Mu.C.H) Technology for the Correction of Facial Ageing Defects

Background: Hyaluronic acid (HA) plays a crucial role in skin health: it moisturizes, supports connective tissue and supports collagen production. With increasing age, HA levels decrease leading to wrinkles and a loss of facial volume. Hyal System DUO, an HA-based filler, addresses these defects through a unique combination of auto-crosslinked HA and BDDE-crosslinked HA. Purpose: To evaluate the safety, tolerability, and long-term performance of the HA-based filler in correcting facial wrinkles and restoring volume, turgor and elasticity to the skin. Materials and Methods: In a single-center observational study, 27 subjects were examined who were treated with the HA-based dermal filler in various areas of the face. Performance was assessed at six visits using the Wrinkle Severity Rating Scale (WSRS), the Facial Volume Loss Scale (FVLS), and the Global Aesthetic Improvement Scale (GAIS). Safety was monitored by recording adverse events. Results: The HA-based filler showed significant and sustained performance in reducing wrinkles and restoring facial volume over the entire study period. Subject satisfaction was consistently high, with self-reported improvements consistent with physician’s assessments. Adverse events were mild and transient, demonstrating the safety of the product. The cross-linking technologies in this HA-based filler contributed to its lasting effect, providing a natural improvement for facial rejuvenation.

Evaluation of the Filling Effects and Safety of an Injectable Gel Based on A Multi-Crosslinked Hyaluronan (Mu.C.H) Technology for the Correction of Facial Ageing Defects

Background: Hyaluronic acid (HA) plays a crucial role in skin health: it moisturizes, supports connective tissue and supports collagen production. With increasing age, HA levels decrease leading to wrinkles and a loss of facial volume. Hyal System DUO, an HA-based filler, addresses these defects through a unique combination of auto-crosslinked HA and BDDE-crosslinked HA. Purpose: To evaluate the safety, tolerability, and long-term performance of the HA-based filler in correcting facial wrinkles and restoring volume, turgor and elasticity to the skin. Materials and Methods: In a single-center observational study, 27 subjects were examined who were treated with the HA-based dermal filler in various areas of the face. Performance was assessed at six visits using the Wrinkle Severity Rating Scale (WSRS), the Facial Volume Loss Scale (FVLS), and the Global Aesthetic Improvement Scale (GAIS). Safety was monitored by recording adverse events.

Abstract 3188: Chitosan-glycerol injectable gel for intratumoral retention of immunotherapeutics

Abstract A novel, injectable chitosan-glycerol hydrogel was developed and characterized. Upon injection with co-formulated therapeutics, the gel vastly improved molecule retention at the injection site, as compared to molecule delivery in less viscous media. Methods. The hydrogel was formed through a centrifugation process. 70% deacetylated, medium viscosity chitosan was dissolved in 0.1M HCl. Glycerol was then added, followed by vortexing. Next, 1x PBS and 1M NaOH were added to neutralize the mixture, which induced gelation. After hydrogel centrifugation at 10,000 rpm for 5 minutes, a hydrogel was separated from precipitate. Several formulation parameters were tested, including chitosan:glycerol volume ratio, chitosan concentration, chitosan degree of deacetylation, and chitosan molecular weight. The retention of model therapeutics, formulated in hydrogel or saline vehicles, following injection in agar-based tumor phantoms was quantified via absorbance and fluorescence readings. To assess biocompatibility, a non-contact cell viability assay was performed utilizing 3T3 fibroblasts seeded in the bottom of transmembrane wells with hydrogels added to the upper chamber. After 48 hours, cells were collected and counted utilizing trypan blue. New Data. A hydrogel for intratumoral therapeutic delivery was constructed with several desirable qualities, including biocompatibility and injectability through a 25-gauge needle. Different relative glycerol to chitosan volumes, from 5 to 95 w/v % glycerol, were tested to determine a range of gelation conditions. Glycerol volume most significantly impacted gelation conditions independent of chitosan concentration, with gelation occurring between 70-85% relative volume glycerol. Increasing chitosan solution concentration and chitosan molecular weight increased the range of chitosan:glycerol ratios resulting in gelation. The hydrogel improved load retention at the agar tumor phantom injection site for various sizes of model therapeutics compared to less viscous solutions. Cytotoxicity testing of the hydrogel showed a statistically insignificant difference between the live:dead cell ratios of the experimental and negative control groups. Conclusion. An injectable, biocompatible hydrogel was created through the neutralization and centrifugation of a chitosan-glycerol solution. The hydrogel displays physiological pH, injectability through a 25-gauge needle, biocompatibility, and vastly improved therapeutic load retention at the injection site compared to less-viscous delivery media. Chitosan-glycerol hydrogels may be useful for intratumoral delivery and retention of immunomodulators within the tumor microenvironment. Citation Format: Robert L. Kobrin, Siena M. Mantooth, David A. Zaharoff. Chitosan-glycerol injectable gel for intratumoral retention of immunotherapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3188.

Injectable Hydrogel Delivery System with High Drug Loading for Prolonging Local Anesthesia.

Peripheral nerve block is performed for precise pain control and lesser side effects after surgery by reducing opioid consumption. Injectable hydrogel delivery systems with high biosafety and moisture content have good clinical application prospects for local anesthetic delivery. However, how to achieve high drug loading and long-term controlled release of water-soluble narcotic drugs remains a big challenge. In this study, heterogeneous microspheres and an injectable gel-matrix composite drug delivery system are designed in two steps. First, heterogeneous hydrogel microspheres loaded with ropivacaine (HMS-ROP) are prepared using a microfluidic chip and in situ alkalization. An injectable self-healing hydrogel matrix (Gel) is then prepared from modified carboxymethylcellulose (CMC-ADH) and oxidized hyaluronic acid (OHA). A local anesthetic delivery system, Gel/HMS-ROP/dexmedetomidine (DEX), with long-term retention and drug release in vivo is prepared by combining HMS-ROP and Gel/DEX. The drug loading of HMS-ROP reached 41.1%, with a drug release time of over 160h in vitro, and sensory and motor blockade times in vivo of 48 and 36h, respectively. In summary, the sequential release and synergistic analgesic effects of the two anesthetics are realized using core-shell microspheres, DEX, and an injectable gel, providing a promising strategy for long-acting postoperative pain management.