Sodium Hyaluronate Gel Research Articles

Determination of Free Polyethylene Glycol in Cross-Linked Sodium Hyaluronate Gel

Abstract: In this study we present a method for the determination of free polyethylene glycol in a gel. We detect the PEG residues of cross-linked sodium hyaluronate gel by spectrophotometry. The pretreatment of cross-linked sodium hyaluronate gel is special and the plot of working curve is unconventional. The precision, the recovery rate with marker, the reliability and repeatability of this method are tested and verified. The results indicated that the method has an excellent linear relationship in the range of 0-40.5µg mL-1. The regression equation is Y=0.0108X+0.2047 (R2=0.9994). The standard deviation of the detection method is 1.10% (n=9). The recovery rate with marker is 97.8% and the repeatability is perfect. In conclusion, the method possesses the properties of simple operation, quickness, excellent stability. Moreover this method can be applied for the quality control of gel products cross-linked by PEG and liquid samples containing PEG.

Recovery from rat sciatic nerve injury in vivo through the use of differentiated MDSCs in vitro

In this study, muscle-derived stem cells (MDSCs) whose differentiation into neuron-like cells was induced by ciliary neurotrophic factor (CNTF) and Salvia (Salvia miltiorrhiza) in vitro were used to repair rat sciatic nerve injuries in vivo, in order to investigate their multifunctional characteristics as pluripotent stem cells. The sciatic nerve in the right side of the lower limb was exposed under the anesthetized condition of 10% chloral hydrate (0.3 ml/100 g) injection into the abdominal cavity. The tissue which was 0.5 cm above the sciatic nerve bifurcation was broken using a hemostat. After induction, MDSCs were transferred in sodium hyaluronate gel and were placed into the damaged area. An untreated control group was also included in this study. The surgical area was sutured after washing with gentamycin sulfate solution. Sciatic nerve function index (SFI) was calculated, electrophysiological tests were performed and the recovery rate of gastrocnemius muscle wet weight was also calculated. Four weeks post-surgery, the SFI and the recovery rate of gastrocnemius muscle wet weight in the MDSC group were significantly higher than those in the control group (P<0.05). MDSCs whose differentiation is induced by CNTF and Salvia play an active role in the repair of peripheral nerve injury.

Dexamethasone Levels and Base-to-Apex Concentration Gradients in the Scala Tympani Perilymph After Intracochlear Delivery in the Guinea Pig

To determine whether intracochlearly applied dexamethasone will lead to better control of drug levels, higher peak concentrations, and lower base-to-apex concentration gradients in the scala tympani (ST) of the guinea pig than after intratympanic (round window [RW]) application. Local application of drugs to the RW results in substantial variation of intracochlear drug levels and significant base-to-apex concentration gradients in ST. Two microliters of dexamethasone-phosphate (10 mg/ml) were injected into ST either through the RW membrane, which was covered with 1% sodium hyaluronate gel or through a cochleostomy with a fluid tight seal of the micropipette. Perilymph was sequentially sampled from the apex at a single time point for each animal, at 20, 80, or 200 min after the injection ended. Results were mathematically interpreted by means of an established computer model and compared with previous experiments performed by our group with the same experimental techniques but using intratympanic applications. Single intracochlear injections of 20 minutes resulted in approximately 10 times higher peak concentrations (on average) than 2 to 3 hours of intratympanic application to the RW niche. Intracochlear drug levels were less variable and could be measured for over 220 minutes. Concentration gradients along the scala tympani were less pronounced. The remaining variability in intracochlear drug levels was attributable to perilymph and drug leak from the injection site. With significantly higher, less variable drug levels and smaller base-to-apex concentration gradients, intracochlear applications have advantages to intratympanic injections. For further development of this technique, it is of importance to control leaks of perilymph and drug from the injection site and to evaluate its clinical feasibility and associated risks.

The Comparison of Physicochemical Properties of Four Cross-Linked Sodium Hyaluronate Gels with Different Cross-Linking Agents

Abstract：PurposeThe physicochemical properties of four Cross-linked sodium hyaluronate gels(CHA) with different cross-linking agents were conpared.In order to research out the different stability and Enzyme-resistant properties of these CHA.Methods The CHA hydrogels were prepared with different cross-linking agents, such as PEG20000, PDE, BDDE and ADH. The optimal reaction conditions were determined by single factor experiment. Dynamic viscosity was tested by Stabinger method. Intrinsic viscosity was tested by Uzziah's viscosity method. The in vitro Enzyme-resistant properties of CHA-gels were analysed by carbazole and spectrophotometry. Results The concentrations of NaOH/HCl, concentrations of HA and the ratio of cross-linking agent to HA were significant conditions which influenced the physicochemical properties of CHA gels. PDE-CHA and PEG20000 gels have best Dynamic viscosity, PDE-CHA gel has best Intrinsic viscosity, ADH-CHA and BDDE-CHA gels have better Enzyme-resistant properties than PEG20000-CHA and PDE-CHA gels.Conclusion The CHA-gel prepared under optimal reaction conditions have different physical and chemical properties, which set foundation for developing double cross-linked gel with both excellent stability and Enzyme-resistant properties.

Sodium Hyaluronate Gel as Mitomycin C Vehicle to Reduce Potential Endothelial Toxicity in Pterygium Surgery

Jun, Li MD, PhD; Jing, Wang MD; Young, Alvin L MMedSc(Hons), FRCSIrel Author Information

Preparation of Cross-Linked Sodium Hyaluronate Gels with Different Molecular Weights of PEG and Research for its Viscoelasticity and Enzyme-Resistant Properties &lt;i&gt;In Vitro&lt;/i&gt;

Abstract: Purpose To screen out the optimal conditions of cross-linking reaction of preparing for an injectable cross-linked sodium hyaluronate gel(CHA-gel) with higher resistance to hyaluronidase and research for its viscoelasticity and anti-enzyme degradation properties. Methods The CHA hydrogels were prepared with different molecular weights of PEG as cross-linking agent, such as PEG400, PEG1000, PEG6000, PEG10000, PEG20000. The optimal preparing conditions were determined by single factor test and orthogonal experiment. The Enzyme-resistant degradation properties in vitro of CHA-gels were analysed by carbazole and spectrophotometry. Its viscoelasticity was also compared with natural HA-gel by Stabinger method. Results the results of range analysis and variance analysis show that the pH of CHA solution and the ratio of cross-linking agent to HA were significant factors. The optimal preparing conditions of the parameters are 1.5% of HA, 0.001mol/L NaOH, at 37°C, reacting 4hr and 1:15 PEG20000/HA (g/g). Under these conditions, the CHA-gel has excellent Enzyme-resistant properties, R=85.1%, an high percentage of enzyme-resistant property. Its viscoelasticity can reach 61.3×104mPa.s, three times as much as natural HA-gel. Conclusion The CHA-gel with excellent physicochemical properties can be prepared under the optimal conditions, which can set foundation for developing better mechanical and Enzyme-resistant properties products of CHA-gel.

Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment

Background and aimsThe mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in...

Assessment of sodium hyaluronate gel as vehicle for intracameral delivery of cefuroxime in endophthalmitis prophylaxis

Sodium cefuroxime is a second-generation cephalosporin widely used at 10mg/mL for endophthalmitis prophylaxis after cataract surgery. Sodium cefuroxime solution is usually conditioned in pre-filled syringes then frozen for storage. In the present study, 0.2% sodium hyaluronate gel, natural extracellular polymer used in wound healing, was compared to conventional saline solution (0.9% sodium chloride) as drug delivery systems for cefuroxime loading in pre-filled syringes. Therefore, the temperature (4 and 25 degrees C) and time of storage (up to 21 days) varied in order to appreciate both cefuroxime and vehicle stability. Furthermore, the kinetics of drug release from both hyaluronate gel and saline solution were compared since in vitro sets of dialysis experiments. Results indicated that cefuroxime loaded in either saline solution or hyaluronate hydrogel was found stable in pre-filled syringes stored at 4 degrees C for 21 days, whereas cefuroxime degradations products appeared from the 2nd day of storage at 25 degrees C. Both drug delivery systems were found bioequivalent, although statistically slower cefuroxime dialysis was evidenced by using sodium hyaluronate vehicle. Noteworthy, cefuroxime concentration in drug delivery systems during dialysis experiment remained greater than the minimum inhibitory concentrations reported for resistant strains. In conclusion, the present stability and release study confirmed that sodium hyaluronate hydrogel is a promising vehicle for cefuroxime intracameral delivery in endophthalmitis prophylaxis.

Middle Ear Application of a Sodium Hyaluronate Gel Loaded with Neomycin in a Guinea Pig Model

Establishing methods for topical administration of drugs to the inner ear have great clinical relevance and potential even in a relatively short perspective. To evaluate the efficacy of sodium hyaluronate (HYA) as a vehicle for drugs that could be used for treatment of inner ear disorders. The cochlear hair cell loss and round window membrane (RWM) morphology were investigated after topical application of neomycin and HYA into the middle ear. Sixty-five albino guinea pigs were used and divided into groups depending on the type of the treatment. Neomycin was chosen as tracer for drug release and pharmacodynamic effect. HYA loaded with 3 different concentrations of neomycin was injected to the middle ear cavity of guinea pigs. Phalloidin stained surface preparations of the organ of Corti were used to estimate hair cell loss induced by neomycin. The thickness of the midportion of the RWM was measured and compared with that of controls using light and electron microscopy. All animal procedures were pe rformed in accordance with the ethical standards of Karolinska Institutet. Neomycin induced a considerable hair cell loss in guinea pigs receiving a middle ear injection of HYA loaded with the drug, demonstrating that neomycin was released from the gel and delivered to the inner ear. The resulting hair cell loss showed a clear dose-dependence. Only small differences in hair cell loss were noted between animals receiving neomycin solution and animals exposed to neomycin in HYA suggesting that the vehicle neither facilitated nor hindered drug transport between the middle ear cavity and the inner ear. One week after topical application, the thickness of the RWM had increased and was dependent upon the concentration of neomycin administered to the middle ear. At 4 weeks the thickness of the RWM had returned to normal. HYA is a safe vehicle for drugs aimed to pass into the inner ear through the RWM. Neomycin was released from HYA and transported into the inner ear as evidenced by hair cell loss.

Sodium hyaluronate gels as a drug‐release system for corticosteroids: release kinetics and antiproliferative potential for glaucoma surgery

To evaluate the release kinetics, biocompatibility and antiproliferative potential of a concentrated hydrophilic steroid formulation from commercially available sodium hyaluronate gels as a potential adjunct in glaucoma surgery. Dexamethasone and sodium hyaluronate 1% (Healon) and sodium hyaluronate 2.3% (Healon 5) were mixed to yield sodium hyaluronate formulations containing dexamethasone in concentrations of 4-20 mg/ml (7.7-38 mm). Non-cumulative and cumulative release into balanced salt solution (BSS) or phosphate buffered saline (PBS) was measured spectrophotometrically over 2-6 days. For cytotoxicity assays, human tenon fibroblasts (HTFB) and human retinal pigment epithelium cells (ARPE19) were cultured in a serum-deficient medium to ensure a static milieu; 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay and Live/Dead cell-mediated cytotoxicity assay were used to exclude cytotoxicity. Cellular proliferative activity was monitored by 5'-bromo-2'-deoxyuridine (BrdU)-incorporation into cellular DNA. The release kinetics from sodium hyaluronate 1% and 2.3% were almost identical. Steady state was achieved after approximately 44 hrs in non-cumulative measurements. The release plotted as a function of the square root of time was consistent with a largely diffusion-controlled release system. No cytotoxicity could be observed. Dexamethasone-loaded sodium hyaluronate showed a significant antiproliferative effect on HTFB and ARPE19 cells. Dexamethasone-loaded sodium hyaluronate shows extended release of steroid over almost 2 days in concentrations high enough to inhibit the proliferation of HTFB and RPE cells without evoking cytotoxic effects. Thus, this formulation may be an easy-to-prepare adjunct in glaucoma surgery or other procedures in which cellular growth inhibition is desired.

The use of sodium hyaluronate for the treatment of radiation recall dermatitis

Hyaluronic acid (HA) is a high-molecular weight polysaccharide, a glycosaminoglycan that enhances fibroblast movement and metabolism during wound healing, increasing collagen fibers forming granulation tissue. We describe a 42-year-old female, who developed radiation recall dermatitis following an allogeneic stem cell transplant from an unrelated donor (MUD-PBSCT). Her skin was treated with a topical sodium hyaluronate gel twice daily (RadiaplexRX, MPM Medical). There was marked improvement after 5 days of therapy without discontinuation of any of her therapeutic agents. At a time when the health care providers were faced with considerable treatment dilemmas, this patient demonstrated improvement in the symptoms of radiation recall dermatitis with the topical application of sodium hyaluronate and no change in her medication profile. This agent could successfully allow practitioners to treat radiation recall dermatitis without discontinuation of the recall trigger drug and thus jeopardizing the outcome of the treatment regimen.

Polyvinylpyrrolidone–sodium hyaluronate gel (Gelclair®): a bioadherent oral gel for the treatment of oral mucositis and other painful oral lesions

Background: Painful oral lesions in patients with cancer, HIV or aphthous ulcers can cause significant pain and discomfort. Those with oral mucositis (OM) resulting from high-dose chemotherapy or irradiation are the most at risk for painful lesions that lead to significant morbidity and mortality, decreased quality of life and increased economic costs. Numerous approaches have been taken to prevent and treat OM in the cancer patient but this condition remains a significant obstacle to cancer therapy. Small studies have been done in healing oral lesions arising from laser surgery and in wound healing but research is needed to support the use of polyvinylpyrrolidone–sodium hyaluronate gel (Gelclair®) in these clinical setting. Objective: The purpose of this paper is to review the benefit of polyvinylpyrrolidone–sodium hyaluronate gel, a topical oral mucosal barrier gel to prevent or diminish the pain of OM and other oral lesions. Methods: Primary resources in peer-reviewed journals, chapters in recognized textbooks and information from international and national oncology and dental medicine scientific meetings. Conclusions: Oncology patients receiving high-dose immunosuppressive therapy are the most at risk with painful OM. Current prevention and treatment options for OM have limited effectiveness. Although opioids are available for pain management, novel agents, to be used alone or in combination with other proven measures to decrease the severity and duration of OM, are emerging. Clinical studies in the use of polyvinylpyrrolidone–sodium hyaluronate to reduce the pain or disruption to the oral mucosa has merit. Few clinical trials or main publications have supported the use of this product. Robust randomized trials are needed to further support the clinical utility of this agent.

Marker retention in the cochlea following injections through the round window membrane

Local delivery of drugs to the inner ear is increasingly being used in both clinical and experimental studies. Although direct injection of drugs into perilymph appears to be the most promising way of administering drugs quantitatively, no studies have yet demonstrated the pharmacokinetics in perilymph following direct injections. In this study, we have investigated the retention of substance in perilymph following a single injection into the basal turn of scala tympani (ST). The substance injected was a marker, trimethylphenylammonium (TMPA) that can be detected in low concentrations with ion-selective microelectrodes. Perilymph pharmacokinetics of TMPA was assessed using sequential apical sampling to obtain perilymph for analysis. The amount of TMPA retained in perilymph was compared for different injection and sampling protocols. TMPA concentrations measured in fluid samples were close to those predicted by simulations when the injection pipette was sealed into the bony wall of ST but were systematically lower when the injection pipette was inserted through the round window membrane (RWM). In the latter condition, it was estimated that over 60% of the injected TMPA was lost due to leakage of perilymph around the injection pipette at a rate estimated to be 0.09 μL/min. The effects of leakage during and after injections through the RWM were dramatically reduced when the round window niche was filled with 1% sodium hyaluronate gel before penetrating the RWM with the injection pipette. The findings demonstrate that in order to perform quantitative drug injections into perilymph, even small rates of fluid leakage at the injection site must be controlled.

Histopathologic study of minced and injected expanded polytetrafluoroethylene (Gore-Tex) in quadriceps muscle of rats for injection laryngoplasty

Objective Gore-Tex has not yet been used as an injection material, and no animal study has been performed. The purpose of this study was to investigate the histopathological and volumetric changes of minced and injected expanded polytetrafluoroethylene (Gore-Tex) in the quadriceps muscle of rats to find out its possibility as an injection material in future injection laryngoplasty. Design A prospective study was performed in 13 Wistar rats. Methods The 50 ± 5 mg Gore-Tex vascular graft was minced until it was fine enough to pass through a 16G injection cannula. To create viscosity in order to avoid precipitation, minced Gore-Tex was mixed with sodium hyaluronate (SH) gel. 0.5 ml of this mixture was injected into the middle part of the right quadriceps muscle of each subject. Then, pure SH (0.5 ml) was injected into the middle part of the left quadriceps muscle of each subject. To compare the volumetric and histopathological changes of the injection area occupied by the materials over the time, two rats were sacrificed 1 day after the procedure, four rats after 1 month, four rats after 3 months and three rats after 6 months. Results In pure SH: SH was observed as an effusion in the muscle of one subject on the first day only. We did not detect SH in the muscle in the first, third and sixth months and, as a result, there was no augmentation. Inflammation and fibrosis was not detected in any of these applications of SH. In minced Gore-Tex + SH gel mixture: SH was again eliminated from the muscle in a very short period of time, but the remaining Gore-Tex created a 15.8% volumetric gain. Fibrosis and capsule formation began in the first month and, in the sixth month; we observed connective tissue surrounding the Gore-Tex material. Ingrowth of connective tissue into the Gore-Tex, though not present in the first month, occurred partially in the third and significantly in the sixth month. In addition, we observed foreign body granuloma formation after the third month. Conclusions Pure SH, though easily applicable, was immediately eliminated leaving no trace. In the relatively difficult applications of Gore-Tex mixed with SH, however, there was residual Gore-Tex present in all subjects throughout the study. Gore-Tex may be an applicable material for injection laryngoplasty.

Hyaluronate Gel Stapedotomy

To evaluate hearing results and postoperative dizziness after stapedotomy with application of sodium hyaluronate gel (HG) to the oval window niche during fenestration of the footplate. Case-control study comparing 27 stapedotomies with HG and 32 stapedotomies without HG. Preoperative and postoperative audiometric data, postoperative dizziness (vertigo or dysequilibrium), and nystagmus. Postoperative hearing results were not statistically different for the 2 groups. There were no cases of postoperative sensorineural hearing loss greater than 10 dB. Early postoperative dizziness (chi(2) = 4.08, P = 0.043) and nystagmus (chi(2) = 5.05, P = 0.024) were reduced in the HG group. HG stapedotomy is safe and effective and results in less early postoperative dizziness and nystagmus when compared with the standard technique of stapedotomy. The application of HG to the oval window niche to prevent blood from entering or perilymph from escaping the vestibule during fenestration of the stapes footplate may contribute to a quicker recovery in outpatient otosclerosis surgery.

Prevention of Peritendinous Adhesions Following Flexor Tendon Injury With Seprafilm

Peritendinous adhesions are the most important complication of flexor tendon injury. In this study, Seprafilm was used for the prevention of peritendinous adhesions following flexor tendon repair. Seprafilm Bioresorbable Membrane (Genzyme Corporation, Cambridge, MA) contains sodium hyaluronate and carboxymethyl cellulose. Thirty New Zealand white male rabbits were divided equally into 3 groups. In all groups, the deep flexor tendon of the third finger of the left back foot was cut and repaired by Kessler-Tajima suture technique. In the first study group following tendon repair, Seprafilm was wrapped around the repaired tendon. In the second study group, sodium hyaluronate gel was injected to the operation field after tendon repair. In the control group, no external material was applied to the field. The study groups had better range of motion. Histopathologically, study groups had less adhesions compared with the control groups. As a result, it was concluded that in rabbit the peritendinous adhesions following flexor tendon repairs could be lowered with Seprafilm and hyaluronic acid.

Spectrophotometric analysis of molecular transport in gels

An automated spectrophotometric method has been developed for analyzing molecular transport out from and into gels. A Beckman DU7500 diode-array UV-visible spectrophotometer with gel scanner was modified to accept and longitudinally scan a quartz diffusion cell, 0.3×10×40 mm. Molecules of interest are identified and concentrations quantitated via analysis of spectrophotometric absorbance peaks relative to background absorbance of the gel. Thus, concentration profiles are obtained as functions of both position and time. Test data are fitted to a diffusion model via nonlinear least-squares regression. Precision and accuracy of the method were assessed via analysis of several test molecules and gels: (1) 30 mg/ml nonoxynol-9 (N9), contained in 1% sodium alginate gel cross-linked with 2.5 mM calcium chloride, permeating standardized, reconstituted bovine cervical mucus (BCM); (2) 2.5 mg/ml sodium fluorescein, contained in and permeating 10 mg/ml and 100 mg/ml gelatin gels; and (3) 1.0 mg/ml sodium ganciclovir, contained in and permeating 10 mg/ml sodium hyaluronate gel. Diffusion coefficients for (1) and (3) were 3.8×10 −7 and 54.1×10 −7 cm 2/s, respectively. All measurements of diffusion coefficients, partition coefficients, and solute loads obtained in this study were highly repeatable (most C.V.'s<8%). The mean diffusion coefficient for (2) was within 3% of values predicted from theory for the 100 mg/ml gel; the mean partition coefficient for (3) was within 2% of the expected value. This new technique is simpler than many traditional ones in that it does not require labeling of test molecules nor changes in refractive index of target materials. It is particularly well-suited to situations in which the target material is a gel, because no stirring of the target is necessary.

In Vitro Release Kinetics of Gentamycin from a Sodium Hyaluronate Gel Delivery System Suitable for the Treatment of Peripheral Vestibular Disease

For certain patients who experience intense vertigo arising from unilateral vestibular lesions, the primary therapy is a vestibular nerve section, an intracranial surgical procedure. One alternative to this treatment is therapeutic ablation of vestibular function on the unaffected side using an ototoxic agent. We prepared a biodegradable sustained-release gel delivery system using sodium hyaluronate that can be administered into the middle ear using only a local anesthetic. The gel contains gentamycin sulfate, the ototoxic agent of choice for treatment of unilateral vestibulopathy, and it exhibits diffusion-controlled release of the drug over a period of hours. The released gentamycin could then diffuse into the inner ear through the round membrane. This represents an important advance over previous formulations, which used only gentamycin sulfate solutions, in that it should allow more careful control of the dose, it should reduce loss of the drug from the middle ear site, and it should maintain intimate contact with the round membrane. By carefully controlling the dose, it should be possible to inhibit vestibular function while minimizing hearing loss. Herein we describe the in vitro release kinetics of gentamycin sulfate from sodium hyaluronate gels and find that the system obeys Fickian behavior.

Potential role of fibroblast growth factor in enhancement of fracture healing.

Fibroblast growth factors are present in significant amounts in bone and several studies have suggested that they may be involved in normal fracture healing. It is well established that fibroblast growth factors have mitogenic and angiogenic activity on mesoderm and neuroectoderm derived cells. Of particular interest as a member of the fibroblast growth factor family, basic fibroblast growth factor stimulates mitogenesis, chemotaxis, differentiation, and angiogenesis. It also plays an important role in the development of vascular, nervous, and skeletal systems, promotes the maintenance and survival of certain tissues, and stimulates wound healing and tissue repair. Animal studies have shown that the direct injection of fibroblast growth factor into fresh fractures stimulates callus formation, which provides mechanical stability to the fracture, accelerates healing, and restores competence. The matrix used to present the fibroblast growth factor at the fracture site plays a critical role in the effectiveness of the treatment. The evaluation of injectable basic fibroblast growth factor in a sodium hyaluronate gel for its effectiveness in stimulating fracture healing is described. When applied directly into a freshly created fracture in the rabbit fibula, a single injection of the basic fibroblast growth factor and hyaluronan results in the stimulation of callus formation, increased bone formation, and earlier restoration of mechanical strength at the fracture site. The hyaluronan gel serves as a reservoir that sequesters the basic fibroblast growth factor at the injection site for the length of time necessary to create an environment conducive to fracture healing. It is concluded that basic fibroblast growth factor and sodium hyaluronate act synergistically to accelerate fracture healing and that the combination is suitable for clinical evaluation as a therapy in fracture treatment.

Effect of highly concentrated gels of sodium hyaluronate on early phases of regeneration in the transected and tubulized rat sciatic nerve

Silicone regeneration chambers prefilled with sodium hyaluronate (HA) gels of different molecular weight (MW) and at different concentrations were used to tubulize the transected rat sciatic nerve. After two weeks, the tissue cables bridging the severed nerve ends within the silicone tubes were examined. Low MW HA gels had no significant effect while high MW HA gels reduced the diameter of the growing bridges.