Injectable Hyaluronic Acid Research Articles

Safety and Effectiveness of a Novel Hyaluronic Acid Gel for Lip Augmentation.

To compare the safety and efficacy of a novel hyaluronic acid injectable gel with 0.3% lidocaine (test device) with that of a commercially available injectable hyaluronic acid gel with 0.3% lidocaine (comparator) for lip augmentation. Eligible patients (n = 158) with an overall score of very thin (n = 0) or thin (n = 1) on a 5-point Lip Fullness Grading Scale (LFGS) participated in the double-blind, randomized, multicenter study. Efficacy was assessed periodically over 6 months on a per protocol (PP) population (definitive) and a modified intent-to-treat (mITT) population (supportive). In the PP population, the mean change from baseline (day 56) in LFGS score was 1.52 for the test device and 1.53 for the comparator. This 56-day change was the primary efficacy endpoint. The 95% confidence interval (CI) limits for the mean difference in scores (test device minus comparator) were -0.33 and 0.31. In the mITT population, the corresponding 95% CI limits were -0.26 and 0.31. In both populations, the lower limits, -0.33 and -0.26, were higher than the prespecified -0.50, indicating that the test device was non-inferior to comparator. The adverse event profile was similar between the treatment groups. Ninety-three percent of patients treated with test device considered themselves improved, much improved, or very much improved at day 168 compared to 82% of those treated with comparator. The corresponding investigator improvement ratings were 100% and 76%, respectively. For lip augmentation, the efficacy and safety of the test device is non-inferior to comparator. J Drugs Dermatol. 2022;21(1):13-20 doi:10.36849/JDD.6548.

Injectable hyaluronic acid hydrogel loaded with BMSC and NGF for traumatic brain injury treatment.

Injectable hydrogel has the advantage to fill the defective area and thereby shows promise as therapeutic implant or cell/drug delivery vehicle for tissue repair. In this study, an injectable hyaluronic acid hydrogel in situ dual-enzymatically cross-linked by galactose oxidase (GalOx) and horseradish peroxidase (HRP) was synthesized and optimized, and the therapeutic effect of this hydrogel encapsulated with bone mesenchymal stem cells (BMSC) and nerve growth factors (NGF) for traumatic brain injury (TBI) mice was investigated. Results from in vitro experiments showed that either tyramine-modified hyaluronic acid hydrogels (HT) or NGF loaded HT hydrogels (HT/NGF) possessed good biocompatibility. More importantly, the HT hydrogels loaded with BMSC and NGF could facilitate the survival and proliferation of endogenous neural cells probably by neurotrophic factors release and neuroinflammation regulation, and consequently improved the neurological function recovery and accelerated the repair process in a C57BL/6 TBI mice model. All these findings highlight that this injectable, BMSC and NGF-laden HT hydrogel has enormous potential for TBI and other tissue repair therapy.

Safety and Effectiveness of a Novel Hyaluronic Acid Gel for Lip Augmentation

Objective: To compare the safety and efficacy of a novel hyaluronic acid injectable gel with 0.3% lidocaine (test device) with that of a commercially available injectable hyaluronic acid gel with 0.3% lidocaine (comparator) for lip augmentation. Methods: Eligible patients (n = 158) with an overall score of very thin (n = 0) or thin (n = 1) on a 5-point Lip Fullness Grading Scale (LFGS) participated in the double-blind, randomized, multicenter study. Efficacy was assessed periodically over 6 months on a per protocol (PP) population (definitive) and a modified intent-to-treat (mITT) population (supportive). Results: In the PP population, the mean change from baseline (day 56) in LFGS score was 1.52 for the test device and 1.53 for the comparator. This 56-day change was the primary efficacy endpoint. The 95% confidence interval (CI) limits for the mean difference in scores (test device minus comparator) were -0.33 and 0.31. In the mITT population, the corresponding 95% CI limits were -0.26 and 0.31. In both populations, the lower limits, -0.33 and -0.26, were higher than the prespecified -0.50, indicating that the test device was non-inferior to comparator. The adverse event profile was similar between the treatment groups. Ninety-three percent of patients treated with test device considered themselves improved, much improved, or very much improved at day 168 compared to 82% of those treated with comparator. The corresponding investigator improvement ratings were 100% and 76%, respectively. Conclusion: For lip augmentation, the efficacy and safety of the test device is non-inferior to comparator. J Drugs Dermatol. 2022;21(1):13-20 doi:10.36849/JDD.6548Hyaluronic Acid Gel

Approach to differentiate between hyaluronic acid skin quality boosters and fillers based on their physicochemical properties.

The clinical indications, applications, and effect of the injectable hyaluronic acid range skin quality boosters (SQBs) are different than those of filler products. Material properties are increasingly being discussed for differentiation and in connection with clinical effects and esthetic indications. The aim of this study is to evaluate whether SQB products can be differentiated from filler products by their physicochemical material properties. Physicochemical properties (extrusion force, swelling degree, rheology, and cohesivity) of two SQBs (BELR , JUVVE ) were compared with those of fillers (BELB , JUVVT ) using the same manufacturing technology. Cohesivity was almost equal for SQBs and fillers. Few statistically significant differences in physicochemical properties were found. Properties of SQBs differed from fillers mainly in their delta of rheological properties and extrusion force. In this study, physicochemical differences between SQB and filler were determined and described, supporting the presence of two categories and their different clinical indications and applications.

Evaluation of the Number, Biophysical and Multipotent Characteristics of Adipose Derived Stem Cells Harvested by SEFFI Procedure and Interaction with Different Type of Hyaluronic Acids

Background: Injection of autologous adipose-derived stem cells (ADSCs) and a stromal vascular fraction (VSF) into dermal and subdermal layers promises regenerative advantages by improving skin volume and rejuvenation. Injectable hyaluronic acid (HA) is a temporary dermal filler that, by improving skin hydration, reduces the appearance of fine lines and wrinkles, facial folds and creates structure and volume to the face and lips. This study combined the grafting of micro fragmented fatty tissue with the hyaluronic acid filler procedure, using three different types of HA. Methods: Each sample of micro fragmented adipose tissue harvested using the superficial enhanced fluid fat injection (SEFFI) technique collected from 8 patients were equally divided into two specimens. One of these (EMU specimens) was emulsified by gently applying ten back-and-forth passages from one syringe to another to fluidify the tissue. The other one was not emulsified (Ctrl/NON-EMU specimen). Both EMU and NON-EMU specimens were divided into four aliquots: one served as control, and the others were combined with each of three tested hyaluronic acids. Afterward, we assessed the cellularity of mesenchymal phenotype (defined as the number of adherent cells with mesenchymal phenotype per milliliter of adipose tissue) and the in vitro capacity of differentiation in mesenchymal lineages. Results: Despite low cellularity from emulsified samples combined with HA, isolated cells could grow and expand in culture, thus proving their proliferative ability, showing “good quality” in all conditions (Ctrl/NON-EMU, EMU, and combined with HA). The cells could differentiate towards mesenchymal lineages, express mesenchymal markers by flow cytometry analysis, and maintain their stemness potential. Conclusion: The combination of emulsified harvested tissue with HA products can be exploited to counteract the loss of volume and skin aging of the human face and body. This approach to regenerative aesthetic treatment is a promising treatment for facial antiaging therapy.

Clinical experience with a new injectable hyaluronic acid designed to improve skin quality in a private clinic in Brazil: A retrospective cohort study.

BackgroundJuvéderm Volite is a skin‐conditioning hyaluronic acid (HA) gel for intradermal injection that provides longer‐lasting effects with a lower concentration of hyaluronic acid. Few studies evaluating its use for aesthetic purposes are available.AimTo examine the use and safety of Juvéderm Volite in daily clinical practice.MethodsA retrospective cohort study of subjects treated with Juvéderm Volite for aesthetic purposes from May 2018 to October 2019 in Rio de Janeiro. Data were extracted from the attending physician's records obtained at each medical appointment. Subjects were assessed according to their age group and treatment characteristics, which include the use of cannulas vs needles and the effectiveness and safety of associated treatments in a single session. Need for subsequent treatment was stratified by touch‐up treatment (<3‐month period) and repeat treatment (≥3‐month period). Safety assessment was based on the report of nodule formation and late hypersensitivity in patients. Appropriate statistical tests were used for data analysis.ResultsOne hundred and eight subjects were included in the study analysis. The total number of treatment sessions consisted of 159, with a mean follow‐up time of 300.3 days. Of the total 108 subjects, 8.4% required touch‐up treatment for optimum correction and repeat treatment occurred in 9.0%. No cases of adverse events were reported during the follow‐up period.ConclusionsThis study has shown, based on clinical observation, that Juvéderm Volite is a useful tool to improve skin quality, requiring fewer and less frequent maintenance treatments. No serious adverse events were reported during the follow‐up period.

Injectable hyaluronic acid hydrogels encapsulating drug nanocrystals for long-term treatment of inflammatory arthritis.

Antiproliferative chemotherapeutic agents offer a potential effective treatment for inflammatory arthritis. However, their clinical application is limited by high systemic toxicity, low joint bioavailability as well as formulation challenges. Here, we report an intra‐articular drug delivery system combining hyaluronic acid hydrogels and drug nanocrystals to achieve localized and sustained delivery of an antiproliferative chemotherapeutic agent camptothecin for long‐term treatment of inflammatory arthritis. We synthesized a biocompatible, in situ‐forming injectable hyaluronic acid hydrogel using a naturally occurring click chemistry: cyanobenzothiazole/cysteine reaction, which is the last step reaction in synthesizing D‐luciferin in fireflies. This hydrogel was used to encapsulate camptothecin nanocrystals (size of 160–560 nm) which released free camptothecin in a sustained manner for 4 weeks. In vivo studies confirmed that the hydrogel remained in the joint over 4 weeks. By using the collagen‐induced arthritis rat model, we demonstrate that the hydrogel‐camptothecin formulation could alleviate arthritis severity as indicated by the joint size and interleukin‐1β level in the harvested joints, as well as from histological and microcomputed tomography evaluation of joints. The hydrogel‐nanocrystal formulation strategy described here offers a potential solution for intra‐articular therapy for inflammatory arthritis.

Comparative Physicochemical Analysis among 1,4-Butanediol Diglycidyl Ether Cross-Linked Hyaluronic Acid Dermal Fillers.

(1) Background: Injectable hyaluronic acid (HA) dermal fillers are used in several chirurgical practices and in aesthetic medicine. HA filler stability can be enhanced through different cross-linking technologies; one of the most frequently cross-linker used is 1,4-butanediol diglycidyl ether (BDDE), also present in the HA-BDDE dermal filler family of the company Matex Lab S.p.A. (Brindisi, Italy). Our overview is focused on their characterization, drawing a correlation between matrix structure, rheological and physicochemical properties related to their cross-linking technologies. (2) Methods: Four different injectable HA hydrogels were characterized through optical microscopic examination and rheological behavior investigation. (3) Results: The cross-linked HA dermal fillers showed a fibrous “spiderweb-like” matrix structure and an elastic and solid-like profile. (4) Conclusions: The comparative analysis represents a preliminary characterization of these injectable medical devices in order to identify their best field of application.

Hierarchically structured injectable hydrogels with loaded cell spheroids for cartilage repairing and osteoarthritis treatment

The repair of cartilage lesions faces challenges in the integration of biological and mechanical cues into scaffolds. Herein, injectable hyaluronic acid (HA) hydrogels were developed with inoculation of bone marrow mesenchymal stem cell (MSC) spheroids and short fiber fillers. Kartogenin (KGN)-loaded short fibers (Fk) are assembled into cell spheroids (Fk-CS) as cell growth substrates and depots of cell differentiation modulators. Celecoxib (CXB)-loaded short fibers (FC) in HA hydrogels (HA-FC) benefit mechanical reinforcement and sustained release of anti-inflammatory agent. After inoculation in hydrogels, Fk-CS up-regulate differentiation-related gene expressions (aggrecan, collagen II, and Sox9) and the sustained release of KGN promotes chondrogenic differentiation and extracellular matrix (ECM) production in the entire spheroids. Osteochondral defects and osteoarthritis model are surgically created and treated with intraarticular injection of Fk-CS-loaded hydrogels. Osteochondral defects are fully repaired with integrated surrounding tissues, and the chondrocyte morphology, ECM (sulfated glycosaminoglycane and collagen II) deposition, and compressive moduli are comparable to those of normal cartilage. Osteoarthritis-derived cartilage lesions are repaired by regenerated ECMs, and osteoarthritis progression is retarded by downregulating pro-inflammatory cytokines and proteinase expressions. Thus, hierarchically structured injectable hydrogels and cell spheroids provide biochemical and mechanical cues for MSC differentiation, ECM deposition, cartilage regeneration, and inflammation removal in the treatment of osteochondral defects and osteoarthritis.

Injectable hydrogel loaded with paclitaxel and epirubicin to prevent postoperative recurrence and metastasis of breast cancer

Post-operative recurrence and metastasis is a major challenge for breast cancer treatment. Local chemotherapy is a promising strategy that can overcome this problem. In this study, we synthesized an injectable hyaluronic acid (HA)-based hydrogel loaded with paclitaxel (PTX) nanoparticles and epirubicin (EPB) (PPNPs/EPB@HA-Gel). PPNPs/EPB@HA-Gel steadily released the encapsulated drugs to achieve long-term inhibition of tumor recurrence and metastasis in a murine post-operative breast tumor model, which prolonged their survival without any systemic toxicity. The drug-loaded hydrogel inhibited the proliferation and migration of tumor cells in vitro, and significantly increased tumor cell apoptosis in vivo. Therefore, PPNPs/EPB@HA-Gel can be used as a local chemotherapeutic agent to prevent postoperative recurrence and metastasis of breast cancer.

Skin wound healing promoted by novel curcumin-loaded micelle hydrogel.

BackgroundThe development of biomaterials with the ability to promote skin wound healing is an important topic in the field of biomedical science. In this study, a topical curcumin (Cur) gel [Cur/hyaluronic acid (HA)] was prepared by combining curcumin-loaded PCL-b-PEG-b-PCL (PECE) nanomicelles (PCEC/Cur) and HA to effectively promote skin wound healing. Continuous drug release from PCEC/Cur can provide long-term protection and treatment of skin wounds.MethodsThe study was completed in two stages. The first stage (in vitro): PCEC/Cur were prepared by thin film hydration method. The second stage (in vivo): 36 anesthetized rats were used to prepare a round full-thickness skin defect wound with a diameter of 23 mm on the dorsal side of the spine, and the rats were randomly divided into 4 groups with 9 rats in each group.ResultsThe results showed that wounds in the Cur/HA group were restored to normal after 14 days after operation, representing 96%±3% wound healing. Hematoxylin and eosin (HE) staining showed that hair follicles in the Cur/HA group were visible and that the re-epithelialization time was earlier. Masson staining showed that Cur/HA promoted the formation of collagen fibers. Immunohistochemical observation showed that angiogenesis and subsequent healing of the wound surface was enhanced in the Cur/HA group.ConclusionsThe injectable hyaluronic acid gel complex Cur/HA is a promising candidate material for a wound dressing to promote healing.

Subcutaneously Injectable Hyaluronic Acid Hydrogel for Sustained Release of Donepezil with Reduced Initial Burst Release: Effect of Hybridization of Microstructured Lipid Carriers and Albumin

The daily oral administration of acetylcholinesterase (AChE) inhibitors for Alzheimer’s disease features low patient compliance and can lead to low efficacy or high toxicity owing to irregular intake. Herein, we developed a subcutaneously injectable hyaluronic acid hydrogel (MLC/HSA hydrogel) hybridized with microstructured lipid carriers (MLCs) and human serum albumin (HSA) for the sustained release of donepezil (DNP) with reduced initial burst release. The lipid carrier was designed to have a microsized mean diameter (32.6 ± 12.8 µm) to be well-localized in the hydrogel. The hybridization of MLCs and HSA enhanced the structural integrity of the HA hydrogel, as demonstrated by the measurements of storage modulus (G′), loss modulus (G″), and viscosity. In the pharmacokinetic study, subcutaneous administration of MLC/HSA hydrogel in rats prolonged the release of DNP for up to seven days and reduced the initial plasma concentration, where the Cmax value was 0.3-fold lower than that of the control hydrogel without a significant change in the AUClast value. Histological analyses of the hydrogels supported their biocompatibility for subcutaneous injection. These results suggest that a new hybrid MLC/HSA hydrogel could be promising as a subcutaneously injectable controlled drug delivery system for the treatment of Alzheimer’s disease.

A dual macrophage polarizer conjugate for synergistic melanoma therapy

Tumor associated macrophages (TAMs) play a paradoxical role in the fate of aggressive tumors like melanoma. Immune modulation of TAMs from the tumor-permissive M2 phenotype to antitumoral M1 phenotype is an emerging attractive approach in melanoma therapy. Resiquimod is a TLR7/8 agonist that shifts the polarization of macrophages towards M1 phenotype. Bexarotene (BEX) is a retinoid that induce the expression of phagocytic receptors in macrophages besides its ability to downregulate the M2 polarization. However, the clinical use of both agents is hindered by poor pharmacokinetic properties. Here, for the first time we repurposed BEX based on its immunomodulatory properties and combined it with RES by designing hyaluronic acid (HA) conjugates of both drugs that act synergistically as a dual macrophage polarizer to promote the M1 phenotype and suppress the M2 phenotype. This combination enhanced the macrophage secretion of proinflammatory cytokines (IL-6 and TNF-α), while suppressing the production of tumor promoting cytokine CCL22. It enhanced the macrophage phagocytic ability and showed superior inhibitory effects against B16F10 cells. In vivo studies on a mouse melanoma model confirmed the superiority of the dual conjugate compared to the single HA-drug conjugates in suppressing the tumor growth. Immunoprofiling of the excised tumors revealed a significant increase in the M1/M2 ratio of TAMs in mice treated with the dual conjugate. Our intravenously injectable HA conjugate of RES and BEX provides a promising immunotherapeutic combination strategy for resetting the M1/M2 ratio, supporting the tumoricidal activity of TAMs for effective melanoma treatment.

Diacerein-Loaded Hyaluosomes as a Dual-Function Platform for Osteoarthritis Management via Intra-Articular Injection: In Vitro Characterization and In Vivo Assessment in a Rat Model.

The application of intra-articular injections in osteoarthritis management has gained great attention lately. In this work, novel intra-articular injectable hyaluronic acid gel-core vesicles (hyaluosomes) loaded with diacerein (DCN), a structural modifying osteoarthritis drug, were developed. A full factorial design was employed to study the effect of different formulation parameters on the drug entrapment efficiency, particle size, and zeta potential. Results showed that the prepared optimized DCN- loaded hyaluosomes were able to achieve high entrapment (90.7%) with a small size (310 nm). The morphology of the optimized hyaluosomes was further examined using TEM, and revealed spherical shaped vesicles with hyaluronic acid in the core. Furthermore, the ability of the prepared DCN-loaded hyaluosomes to improve the in vivo inflammatory condition, and deterioration of cartilage in rats (injected with antigen to induce arthritis) following intra-articular injection was assessed, and revealed superior function on preventing cartilage damage, and inflammation. The inflammatory activity assessed by measuring the rat’s plasma TNF-α and IL-1b levels, revealed significant elevation in the untreated group as compared to the treated groups. The obtained results show that the prepared DCN-loaded hyaluosomes would represent a step forward in the design of novel intra articular injection for management of osteoarthritis.

Physicochemical Properties of Injectable Hyaluronic Acid: Skin Quality Boosters

AbstractIn addition to clinical research on the efficacy and compatibility of injectable hyaluronic acid (HA) based fillers, ample in vitro research on the physicochemical properties of these materials is published. Different HA‐based product ranges are also available as skin quality boosters (SQBs) to improve skin quality. The aim of this study is to investigate the physicochemical properties of specific HAs for improving skin quality, as, to the best of the authors' knowledge, no data is published on this topic to date. This paper may provide a better understanding of clinical performance and differentiation between these SQBs. Five HA injectable hydrogels (Belotero Revive, Juvederm Volite, Restylane Skinbooster Vital, Viscoderm Hydrobooster, and Profilho) from the SQB product ranges of different companies and manufacturing technologies are investigated for their extrusion force, swelling degree, rheological performance, and cohesivity. There are significant differences in extrusion force, swelling degree, rheological performance, and cohesivity between the assessed SQBs. HA concentration (mg mL−1) exhibits statistically significant positive correlations with extrusion force, swelling degree, tan delta, and cohesivity. This study provides a physicochemical characterization of different SQBs and information to improve understanding of this type of product.

Toward Physicochemical and Rheological Characterization of Different Injectable Hyaluronic Acid Dermal Fillers Cross-Linked with Polyethylene Glycol Diglycidyl Ether.

(1) Background: Injectable hyaluronic acid (HA) dermal fillers are used to restore volume, hydration and skin tone in aesthetic medicine. HA fillers differ from each other due to their cross-linking technologies, with the aim to increase mechanical and biological activities. One of the most recent and promising cross-linkers is polyethylene glycol diglycidyl ether (PEGDE), used by the company Matex Lab S.p.A., (Brindisi, Italy) to create the HA dermal filler PEGDE family. Over the last few years, several studies have been performed to investigate the biocompatibility and biodegradability of these formulations, but little information is available regarding their matrix structure, rheological and physicochemical properties related to their cross-linking technologies, the HA content or the degree of cross-linking. (2) Methods: Seven different injectable HA hydrogels were subjected to optical microscopic examination, cohesivity evaluation and rheological characterization in order to investigate their behavior. (3) Results: The analyzed cross-linked dermal fillers showed a fibrous “spiderweb-like” matrix structure, with each medical device presenting different and peculiar rheological features. Except for HA non cross-linked hydrogel 18 mg/mL, all showed an elastic and cohesive profile. (4) Conclusions: The comparative analysis with other literature works makes a preliminary characterization of these injectable medical devices possible.

Prevention and Management of Filler Induced Iatrogenic Stroke of the Eye [Formula: see text

In the past few decades, minimally-invasive esthetic treatments and the use of injectable Hyaluronic Acid Gels and other filling agents to treat facial esthetics have increased dramatically. Although extremely rare, a filler can cause ocular and orbital ischemia by retrograde flow from the ophthalmic artery when injected in any of the anastomosis of the face. Once filler reaches the central retinal artery, blindness is inevitable, and no treatment is effective. While the risk of blindness happening with any filler injection is rare, the life-altering irreversible consequence of a procedure that was anticipated to be simple and beautifying is a reality that each injector must be prepared for with every injection. The parameters associated with an iatrogenic stroke of the eye are the site of injection, the injection technique, patient characteristics, and the material injected. Understanding the interplay of each of these variables might help us reduce the possibility of blindness during the injection of a soft-tissue cosmetic filler. Here, we explore the causes of Hyaluronic Acid Gels Filler embolic phenomena, review the natural course of the process, and discuss appropriate immediate interventions. We also (1) propose an education plan for injectors and describe how to carry out a focused ophthalmologic examination and procedural activities for a referral to an ophthalmologist, (2) outline steps to prevent emboli during filler injection, and (3) how to manage and support a patient with a sudden loss of vision during or immediately after a Hyaluronic Acid Gels filler treatment.

Injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cord.

Biomaterials are being developed as therapeutics for spinal cord injury (SCI) that can stabilize and bridge acute lesions and mediate the delivery of transgenes, providing a localized and sustained reservoir of regenerative factors. For clinical use, direct injection of biomaterial scaffolds is preferred to enable conformation to unique lesions and minimize tissue damage. While an interconnected network of cell-sized macropores is necessary for rapid host cell infiltration into—and thus integration of host tissue with—implanted scaffolds, injectable biomaterials have generally suffered from a lack of control over the macrostructure. As genetic vectors have short lifetimes in vivo, rapid host cell infiltration into scaffolds is a prerequisite for efficient biomaterial-mediated delivery of transgenes. We present scaffolds that can be injected and assembled in situ from hyaluronic acid (HA)-based, spherical microparticles to form scaffolds with a network of macropores (∼10 μm). The results demonstrate that addition of regularly sized macropores to traditional hydrogel scaffolds, which have nanopores (∼10 nm), significantly increases the expression of locally delivered transgene to the spinal cord after a thoracic injury. Maximal cell and axon infiltration into scaffolds was observed in scaffolds with more regularly sized macropores. The delivery of lentiviral vectors encoding the brain-derived neurotrophic factor (BDNF), but not neurotrophin-3, from these scaffolds further increased total numbers and myelination of infiltrating axons. Modest improvements to the hindlimb function were observed with BDNF delivery. The results demonstrate the utility of macroporous and injectable HA scaffolds as a platform for localized gene therapies after SCI.

Minimally invasive therapy for reconstruction of lost interdental papilla by using injectable hyaluronic acid filler.

Background and Aim:Reconstruction of interdental papillae (IDP) is among the most difficult periodontal therapy. Papillary recession is multifactorial, and several surgical, nonsurgical, and minimally invasive techniques have been suggested. The purpose of this study was to evaluate the clinical application of injectable hyaluronic acid (HA) gel for the reconstruction of IDP in Nordland and Tarnow's Class I and II papillary recession cases.Materials and Methods:In the present in vivo clinical trial, 7 patients (2 males, 5 females) with 25 defects were selected. A volume of 0.2 ml HA gel was injected at the respective areas and massaged for 2–3 min. Photographs were obtained, and the assessment of the data was performed clinically (CP-GM, interproximal width [IPW]) and by Image analysis software (black triangle height [BTH], black triangle width [BTW]). Comparison of mean values was performed using the analysis of variance, followed by Post hoc Bonferroni test. Value of P ≤ 0.05 was considered statistically significant.Results:Application of HA gel for the reconstruction of IDP was successful in 6 months. CP-GM, BTH, IPW, and BTW showed a statistically significant difference from baseline to 3 and 6 months interval (P = 0.01). Post hoc Bonferroni test for CP-GM, BTH, BTW, and IPW revealed a statistically significant difference from baseline to 3 months (P ≤ 0.05) and 6 months (P ≤ 0.05) and a nonsignificant difference at 3–6 months (P ≥ 0.05).Conclusion:Injectable HA gel is a promising minimally invasive therapy for enhancing papillary esthetics.

An Injectable Hyaluronic Acid Hydrogel Promotes Intervertebral Disc Repair in a Rabbit Model.

An in vivo model to study the effect of an injectable hyaluronic acid (HA) hydrogel following puncture-induced lumbar disc injury in rabbits. The aim of this study was to determine the efficacy of an injectable HA hydrogel to maintain disc height and tissue hydration, promote structural repair, and attenuate inflammation and innervation in the lumbar discs. Previously, we have demonstrated that HA hydrogel alleviated inflammation, innervation, and pain to promote disc repair. Nevertheless, the effect of an injectable HA hydrogel in the lumbar disc in a weight-bearing animal model was not performed. We have adopted a surgically puncture-induced disc injury at lumbar levels in a rabbit model. The discs were grouped into sham, puncture with water injection, and puncture with HA hydrogel injection. Postoperatively, we measured changes in disc height using x-ray. We used magnetic resonance imaging to assess disc degeneration on tissue hydration after euthanasia. Post-mortem, we determined histological changes, innervation (PGP9.5) and inflammation (interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]-α) in the discs. We have demonstrated a significant reduction of disc height and T2/T1ρ mapping with histological evidence of degenerative discs, increase of innervation and inflammation in puncture-induced disc injury over time. In the HA hydrogel group, disc height was increased at weeks four and eight. A slight increase of T2 mapping, but significantly in T1ρ mapping, was observed in the HA hydrogel group at week 8. We observed homogenous NP distribution and organised AF lamellae at week eight and a slight reduced innervation score in the treatment group. HA hydrogel significantly downregulated IL-6 expression at day 1. This, however, was only slightly reduced for IL-1β and TNF-α. An injectable HA hydrogel had the protective effects in suppressing the loss of disc height, promoting tissue hydration for structural repair, and attenuating inflammation and innervation to prevent further disc degeneration.Level of Evidence: N/A.