Evaluation of the efficacy, safety and satisfaction rates of platelet-rich plasma, non-cross-linked hyaluronic acid and the combination of platelet-rich plasma and non-cross-linked hyaluronic acid in patients with burn scars treated with fractional CO2 laser: A randomized controlled clinical trial.

Skin scarring can result from burns, injuries, stretch marks and acne, leading to cosmetic and functional difficulties. Treatments for burn scars encompass a range of options, such as lasers, corticosteroid injections, surgery and regenerative techniques such as platelet-rich plasma (PRP). Hyaluronic acid-based products offer skin hydration and shield against aging effects. A study is being conducted to evaluate how effective PRP injection, hyaluronic acid and their combination improve burn scars and their effects on quality of life and potential disabilities. In our study, PRP and non-cross-linked hyaluronic acid treatments were compared in 10 individuals with burn scars between 2022 and 2023. Patients received CO2 fractional laser treatment followed by injections in scar areas. Evaluations included the Vancouver scar scale (VSS), biometric assessments, ultrasounds and satisfaction ratings. Two therapy sessions were conducted at 1-month interval, and assessments were done before treatment, 1 month after the first session, and 3 months after the first session. Biometric assessments showed significant improvements in various parameters (tewametry, corneometry, erythema index, melanin index, cutometry, thickness and density) in the intervention groups compared to the placebo group (p <0.05). PRP-non-cross-linked hyaluronic acid, PRP and non-cross-linked hyaluronic acid treatments exhibited the best clinical responses with significant differences between groups (p <0.05). Dermal thickness did not show significant improvement during treatment sessions, and changes among subjects were not significantly different. The colorimetry parameter improved in all groups except the placebo group, with no significant difference between intervention groups. The VSS significantly decreased in all treatment groups except the placebo group. PRP, non-cross-linked hyaluronic acid and especially the combination of these two treatment options are very effective in treating burn scars.

Efficacy and safety of non-cross-linked hyaluronic acid compound in the treatment of keratosis pilaris: A split-body randomized clinical trial.

BACKGROUND: Keratosis pilaris (KP) is a prevalent benign dermatological condition characterized by small bumps at the hair follicles alongside surrounding redness, significantly impacting both aesthetics and mental well-being. OBJECTIVE: This study investigated the potential benefits of a non-cross-linked hyaluronic acid (HA) compound for treating KP. METHODS: A split-body, investigator-blinded, randomized, intraindividual comparative clinical trial was conducted. The non-cross-linked HA compound was injected into KP-affected regions on both upper arms. The treatment was delivered across four sessions scheduled at 4-week intervals. Blinded physicians and patients assessed differences in erythema, skin roughness, and overall scores between treated and control areas at the final follow-up visit. At the 12th and 24th weeks post-treatment, a four-point scale was utilized to assess subjects' perceived treatment efficacy. Additionally, dermoscopic images, histological alterations, and adverse events were monitored. RESULTS: Physician assessments revealed a significant reduction in roughness and overall scores for treated areas compared to controls. Patient self-assessments also reflected improvements in roughness, redness, and overall scores for treated sides at the final visit, with 35.71% of patients demonstrating sustained improvement in redness and 71.43% reporting persistent improvements in roughness at 24th weeks post-treatment. The dermatoscopic examinations revealed a notable enhancement in both the quantity of follicular plugs and the extent of erythema among the subjects in the treatment group. Histopathological outcomes also demonstrated improvement. CONCLUSION: This study suggests that the non-cross-linked HA compound effectively improves skin roughness and promotes hair shaft growth in KP treatment, demonstrating a favorable safety profile. These findings position it as a potentially viable alternative therapy in clinical practice.

Clinical efficacy and safety of composite non-cross-linked hyaluronic acid for treating tear trough-lower eyelid bag deformity.

BACKGROUND: Tear trough-eye bag deformities may appear in young Asian patients due to the weak support of their facial skeletons. For these patients with better periorbital skin elasticity, the injection may be more suitable than surgery for treating tear trough-lower eyelid bag deformity. AIMS: Identify the clinical efficacy and safety of non-cross-linked HA in the treatment of tear trough-lower eyelid bag deformity. METHODS: In this study, we analyzed pre- and postinjection photographs of 55 patients treated with non-cross-linked hyaluronic acid (HA) for tear trough-lower eyelid bag deformity. RESULTS: The mean [SD] scores of modified Goldberg score suggested that the most significant improvement of preoperative and postoperative scores was in tear trough depression, followed by infraorbital triangular depression, orbital fat prolapse, loss of skin elasticity, and skin transparency. Only transient localized complications were observed, including bruising, swelling, and erythema. There were no serious complications, such as skin necrosis or visual impairment. CONCLUSIONS: Our study confirmed the beneficial efficacy and minor complications of composite non-cross-linked HA for the treatment of tear trough-lower eyelid bag deformity.

Evaluation and comparison of the efficacy and safety of cross-linked and non-cross-linked hyaluronic acid in combination with botulinum toxin type A in the treatment of atrophic acne scars: A double-blind randomized clinical trial.

INTRODUCTION: Acne vulgaris is a common skin condition that affects a significant percentage of adolescents, with scarring being one of its permanent complications. This study aims to compare the efficacy and safety of using botulinum toxin type A (BTA) in combination with cross-linked and non-cross-linked hyaluronic acid (HA) for the treatment of atrophic acne scars. METHOD: Our study is a randomized, double-blind clinical trial conducted on 16 patients with atrophic acne scars. The patients were randomly assigned to one of two groups: one group received a single session of BTA and crossed link HA combination, while the other group received two sessions of BTA and non-crossed link HA, 1 month apart. The patients were followed up at 3 and 6 months after baseline to evaluate the number and area of fine and large pores and spots, scar grading, patient satisfaction, and complications. RESULTS: The mean age of individuals in both the cross-linked HA and non-cross-linked HA groups was 32.75 ± 4.26 and 31.50 ± 8.48 years, respectively (p = 0.71). In terms of gender, three (37.5%) and seven (87.5%) individuals in the cross-linked and non-cross-linked HA groups were female, respectively (p = 0.11). There were no significant differences in the count and area of fine and large pores and spots between the two groups at baseline and the first follow-up session. However, in the second follow-up session, the non-cross-linked HA group had significantly better results than the cross-linked HA group in terms of large pores count and area (p = 0.01). In terms of changes over time, the non-cross-linked HA group showed significantly better improvements in the count and area of large pores compared to the cross-linked HA group (p = 0.03). Additionally, both groups experienced a significant decrease in the count and area of fine pores over time (p = 0.001), but the amount of changes was not statistically significant between the two groups (p = 0.06). Concerning acne grade, initially, 62.5% and 12.5% of cases in the cross-linked HA and non-cross-linked HA groups, respectively, had severe grades. However, in the last session, these percentages significantly decreased to 0% for both groups (p = 0.002 and 0.005, respectively). In terms of treatment complications, none of the patients experienced any adverse effects. CONCLUSION: The study demonstrated that both cross-linked HA and non-cross-linked HA were effective in reducing acne severity and improving the appearance of pores and spots. The treatments had similar effects on fine pores, spots, and overall acne severity. However, non-cross-linked HA appeared to have a better result on large pores compared to cross-linked HA.

Efficacy of autologous platelet-rich plasma combined with a non-cross-linked hyaluronic acid compound in the treatment of female androgenetic alopecia: A retrospective, case-series study.

BACKGROUND: Female androgenetic alopecia (FAGA) is a condition that affects women and involves the gradual loss of terminal hair in specific areas of the scalp. The limited treatment options for FAGA necessitate the development of new strategies. This study aimed to evaluate the potential benefit of using a combination therapy composed of autologous platelet-rich plasma (PRP) and a non-cross-linked hyaluronic acid (HA) compound in the treatment of FAGA. METHODS: This was a retrospective, case-series study, which enrolled nine female patients with FAGA between September 2021 and December 2022. The non-cross-linked HA compound (Hearty®, Imeik Technology Development Co., Ltd.) and PRP were implanted into the areas of hair loss over four treatment sessions separated by 4-week intervals. Patients were monitored for overall improvement in their hair loss, hair count, treatment satisfaction, and adverse events at 1, 3, and 6 months follow-up. RESULTS: The improvement rates, subjectively evaluated by the study physician, were 88.89% at the 1-month and 100% at the 3-month follow-up, relative to baseline. Moreover, the quantitative evaluation results showed that the FAGA patients' hair density increased by 54.51% at the 1-month and by 77.25% at the 3-month follow-up. CONCLUSION: The combination of PRP and non-cross-linked HA compound appeared to be a certain positive effective procedure for FAGA without serious adverse event. We envisage that this work will contribute to the development of new treatment options for women suffering from this condition.

The Effects of a Non-crossed-linked Hyaluronic Acid Gel on the Aging Signs of the Face versus Normal Saline: A Randomized, Double-blind, Placebo-controlled, Split-faced Study.

Background: Skin bio-revitalization improves skin quality globally; it permits the rejuvenation of the skin by increasing hydration and by reconstructing an optimal physiological environment for the skin cells together with a micro-filling effect. Objective: To assess the comparative efficacy of a non-cross-linked hyaluronic acid (NCHA) preparation (M-HA®10, FILLMED Laboratories, France) on fine lines reduction and on skin hydration, radiance and mechanical properties, after three sessions of multiple intradermal injections, active versus placebo, on the face of subjects presenting aging signs. Methods: Thirty healthy subjects received filler injections on one side and a control solution (saline) on the contralateral side of the face. Fine lines depth, skin hydration, and mechanical properties were evaluated using instrumental methods. Skin radiance, cheek fold and crow's feet were scored clinically. In addition, Investigator and subject satisfaction rates were evaluated by the Global Aesthetic Improvement Scale and a subject self-assessment questionnaire. Results: Ten days after the last multi-injection session, the following significant results were observed compared to the control: a reduction of both crow's feet wrinkle depth (in the 110 to 1000µm range, -10% for NCHA and +7% for control) and clinical scoring of cheek wrinkles, and increases in skin radiance and hydration (+35%) and also skin firmness (+27%). The Investigator found that NCHA either improved or much improved the aesthetic aspect on 82% of subjects whereas no improvement was found on the saline side. Subjects found that NCHA significantly reduced wrinkles and increased both skin firmness and elasticity. Conclusion: Intradermal injection of NCHA can improve the quality of facial skin with aging signs by reducing fine wrinkles and improving hydration, firmness and radiance.

Clinical Efficacy and Safety of Non-Cross-Linked Hyaluronic Acid Combined with L-carnosine for Horizontal Neck Wrinkles Treatment.

Background Horizontal neck wrinkle formation is gaining more attention among cosmetic practitioners and clients. To date, hyaluronic acid products are one of the most common treatment options for this aesthetic concern. However, different therapeutic strategies should be given to solve the problem due to multiple etiological reasons. Given that oxidative damage plays a critical role in neck wrinkle formation, anti-oxidative compounds are now considered by physicians when making a treatment plan. Aims To evaluate the efficacy and safety of a non-cross-linked hyaluronic acid filler in combination with L-carnosine in treating horizontal neck wrinkles. Methods Thirteen patients with a Wrinkle Assessment Scale (WAS) of 2-5 for horizontal neck wrinkles were treated with L-carnosine-containing non-cross-linked hyaluronic acid. Participants were followed-up for 3 months after treatment. The post-treated WAS scores evaluated by physicians were collected when patient satisfaction was surveyed. Any post-treatment adverse events were recorded. Results With a single injection of the above filler, the physician-evaluated WAS scores improved by at least one score at one month and the improvement kept consistent as far as three months after injection. According to the last follow-up visit, 11/13 patients were satisfied with the treatment effect of their neck wrinkle. Moreover, adverse events were rare after filler injection, except for local complications that were considered common reactions to the filler injection procedure. Conclusion The non-cross-linked hyaluronic acid filler containing L-carnosine is safe and effective for treating horizontal neck wrinkles.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Non-cross-linked biological mesh in complex abdominal wall hernia: a cohort study.

PURPOSE: Complex abdominal wall hernia repair (CAWHR) is a challenging procedure. Mesh prosthesis is indicated, but the use of synthetic mesh in a contaminated area may add to overall morbidity. Biological meshes may provide a solution, but little is known about long-term results. The aim of our study was to evaluate clinical efficacy and patient satisfaction following Strattice™ (PADM) placement. METHODS: In this cohort study, all patients operated for CAWHR with PADM in three large community hospitals in Germany were included. Patients underwent abdominal examination, an ultrasound was performed, and patients completed quality-of-life questionnaires. The study was registered in ClinicalTrials.gov under Identifier NCT02168231. RESULTS: Twenty-seven patients were assessed (14 male, age 67.5 years, follow-up 42.4 months). The most frequent postoperative complication was wound infection (39.1%). In no case, the PADM had to be removed. Four patients had passed away. During outpatient clinic visit, six out of 23 patients (26.1%) had a recurrence of hernia, one patient had undergone reoperation. Five patients (21.7%) had bulging of the abdominal wall. Quality-of-life questionnaires revealed that patients judged their scar with a median 3.5 out of 10 points (0 = best) and judged their restrictions during daily activities with a median of 0 out of 10.0 (0 = no restriction). CONCLUSIONS: Despite a high rate of wound infection, no biological mesh had to be removed. In some cases, therefore, the biological meshes provided a safe way out of desperate clinical situations. Both the recurrence rate and the amount of bulging are high (failure rate 47.8%). The reported quality of life is good after repair of these complex hernias.

Dual-targeting and microenvironment-responsive micelles as a gene delivery system to improve the sensitivity of glioma to radiotherapy.

Dbait is a small double-stranded DNA molecule that has been utilized as a radiosensitizer to enhance the sensitivity of glioma to radiotherapy (RT). However, there is no effective drug delivery system to effectively overcome the blood-brain barrier (BBB). The aim of this study was to develop a gene delivery system by using the BBB and glioma dual-targeting and microenvironment-responsive micelles (ch-Kn(s-s)R8-An) to deliver Dbait into glioma for RT. Angiopep-2 can target the low-density lipoprotein receptor-related protein-1 (LRP1) that is overexpressed on brain capillary endothelial cells (BCECs) and glioma cells. In particular, due to upregulated matrix metalloproteinase 2 (MMP-2) in the tumor microenvironment, we utilized MMP-2-responsive peptides as the enzymatically degradable linkers to conjugate angiopep-2. The results showed that ch-Kn(s-s)R8-An micelles maintained a reasonable size (80-160 nm) with a moderate distribution and a decreased mean diameter from the cross-linking as well as exhibited low critical micelle concentration (CMC) with positive surface charge, ranging from 15 to 40 mV. The ch-K5(s-s)R8-An/pEGFP showed high gene transfection efficiency in vitro, improved uptake in glioma cells and good biocompatibility in vitro and in vivo. In addition, the combination of ch-K5(s-s)R8-An/Dbait with RT significantly inhibited the growth of U251 cells in vitro. Thus, ch-K5(s-s)R8-An/Dbait may prove to be a promising gene delivery system to target glioma and enhance the efficacy of RT on U251 cells.

Evaluation of changes in skin biophysical parameters and appearance after pneumatic injections of non-cross-linked hyaluronic acid in the face.

BACKGROUND: Pneumatic injections of non-cross-linked hyaluronic acid are effective in skin rejuvenation, however, the associated biophysical parameters and appearance have not been evaluated. OBJECTIVES: To determine the changes in skin biophysical parameters after facial pneumatic injections of non-cross-linked hyaluronic acid. PATIENTS AND METHODS: Twenty-eight healthy female volunteers received pneumatic injections of non-cross-linked hyaluronic acid into the face for consecutive 5 weeks. Skin biophysical parameter assessment and clinical evaluation were performed using the CK Multi-Probe Adapter and Visia system. Five of the volunteers also underwent retroauricular skin biopsy before and after the last treatment. The skin tissues were all stained with Masson-trichrome, Verhoeff-van Gieson stain, and hematoxylin-eosin to evaluate the changes in collagen, elastic fibers, and the epidermis, before and after the last treatment. RESULTS: Transepidermal water loss was significantly lower in week 4 (18.46 ± 4.70 g/h/m2) than at the baseline (22.03 ± 7.15 g/h/m2, p < 0.05). Skin texture was better in week 4 (599.29 ± 354.32) than at the baseline (668.43 ± 342.55, p < 0.05). Skin pores also improved significantly at week 4 (934.07 ± 458.78) compared to the baseline (1024.57 ± 415.31, p < 0.05). Skin wrinkles were improved at the 3-month follow-up (29.29 ± 11.11) compared to the baseline (35.83 ± 16.05, p < 0.05). CONCLUSION: Pneumatic injections of non-cross-linked hyaluronic acid improved skin TEWL, texture, pores, and wrinkles.

Effect of non-cross-linked calcium on characteristics, swelling behaviour, drug release and mucoadhesiveness of calcium alginate beads.

In this study, ibuprofen-loaded calcium alginate beads (CABs) with varying amounts of non-cross-linked calcium (NCL-Ca) were prepared using different washing methods. The influence of NCL-Ca on beads properties was investigated. Increasing the number or duration of washes led to significant decreases in the amount of NCL-Ca whereas the impact of the volume of washes was not significant. Approximately 70% of the initial amount of Ca(2+) was NCL-Ca which was removable by washing while only 30% was cross-linked (CL-Ca). Ca(2+) release from the CABs was bimodal; NCL-Ca was burst-released followed by a slower release of CL-Ca. Washing methods and the amount of NCL-Ca had significant influences on the encapsulation efficiency, beads weight, beads swelling, drug release profile and the mucoadhesiveness of CABs. This study highlighted the importance of washing methods and the amount of NCL-Ca to establish CABs properties and understand their behaviour in the simulated intestinal fluids (SIFs).

Therapeutic Potential of Human Adipose-Derived Stem/Stromal Cell Microspheroids Prepared by Three-Dimensional Culture in Non-Cross-Linked Hyaluronic Acid Gel.

UNLABELLED: Three-dimensional culture of mesenchymal stem/stromal cells for spheroid formation is known to enhance their therapeutic potential for regenerative medicine. Spheroids were prepared by culturing human adipose-derived stem/stromal cells (hASCs) in a non-cross-linked hyaluronic acid (HA) gel and compared with dissociated hASCs and hASC spheroids prepared using a nonadherent dish. Preliminary experiments indicated that a 4% HA gel was the most appropriate for forming hASC spheroids with a relatively consistent size (20-50 µm) within 48 hours. Prepared spheroids were positive for pluripotency markers (NANOG, OCT3/4, and SOX-2), and 40% of the cells were SSEA-3-positive, a marker of the multilineage differentiating stress enduring or Muse cell. In contrast with dissociated ASCs, increased secretion of cytokines such as hepatocyte growth factor was detected in ASC spheroids cultured under hypoxia. On microarray ASC spheroids showed upregulation of some pluripotency markers and downregulation of genes related to the mitotic cell cycle. After ischemia-reperfusion injury to the fat pad in SCID mice, local injection of hASC spheroids promoted tissue repair and reduced the final atrophy (1.6%) compared with that of dissociated hASCs (14.3%) or phosphate-buffered saline (20.3%). Part of the administered hASCs differentiated into vascular endothelial cells. ASC spheroids prepared in a HA gel contain undifferentiated cells with therapeutic potential to promote angiogenesis and tissue regeneration after damage. SIGNIFICANCE: This study shows the therapeutic value of human adipose-derived stem cell spheroids prepared in hyarulonic acid gel. The spheroids have various benefits as an injectable cellular product and show therapeutic potential to the stem cell-depleted conditions such as diabetic chronic skin ulcer.

Non-cross-linked polystyrene-supported 2-imidazolidinone chiral auxiliary: synthesis and application in asymmetric alkylation reactions.

Asymmetric alkylation reactions using non-cross-linked polystyrene (NCPS)-supported 2-imidazolidinone chiral auxiliaries were successfully investigated with excellent diastereocontrol (>99% de). The recovery and the recycling of this soluble polymer-supported chiral auxiliary were achieved in order to produce highly optical pure carboxylic acids.