Enhanced Collagen Production Research Articles

Milk-Based Ointment Accelerates Wound Healing: A Comparative Study in Rabbits

Background: Wound healing is a multi-stage process that restores tissue integrity following injury. While chemical treatments like phenytoin aid in healing, traditional remedies, such as milk-based applications, remain underexplored. Milk, particularly its proteins, is known for promoting tissue repair and collagen synthesis. This study evaluated the wound-healing efficacy of a milk-based ointment (MO) on open skin wounds in rabbits. Methods: Male New Zealand white rabbits were randomly assigned to six groups, including negative controls, placebo (eucerin), and 1% phenytoin, alongside three MO groups (2%, 5%, 10% concentrations). The treatments were applied twice daily for 14 days. Wound healing was assessed through macroscopic analysis, tensile strength measurement, hydroxyproline levels, and histological examination. Results: The 5% MO-treated group exhibited the fastest wound healing, achieving full closure in 15 days, outperforming both controls and the phenytoin-treated group (17 days). Hydroxyproline levels and tensile strength were significantly higher in the 5% MO group, indicating enhanced collagen production and stronger tissue regeneration. Histological analysis further confirmed accelerated epithelialization and granulation in MO-treated groups. Conclusion: The study demonstrated that milk-based ointments, particularly at a 5% concentration, significantly enhance wound healing, suggesting their potential as cost-effective, biocompatible alternatives to conventional chemical treatments like phenytoin. Further research is needed to explore clinical applications in humans.

Exploring the potential mechanisms of the ethyl acetate fraction of Hippophae rhamnoides L. seeds as a natural healing agent for wound repair

Ethnopharmacological relevanceSea buckthorn (Hippophae rhamnoides L.) has been designated a "medicine food homology" fruit by the National Health Commission of China due to its nutritional value. In traditional Chinese ethnomedicine, Hippophae rhamnoides L. is commonly used to treat nonhealing wounds such as burns, sores, and gastric ulcers. The aim of this study was to explore the healing effects of the ethyl acetate extract of sea buckthorn seeds (SBS-EF) on burn wounds. Aim of the studyThe primary objectives of this research were to determine the most effective medicinal site of action for treating burns with sea buckthorn seeds (SBS) and to investigate the underlying material basis and mechanisms of their therapeutic effects. Materials and methodsThe effects of different components of SBS-EF on the proliferation and migration of human skin fibroblasts (HSFs) were evaluated via MTT assays, scratch assays, transwell assays, and hydroxyproline secretion analysis. SBS-EF displayed the greatest activity amongst the extracts. Subsequent analyses included network pharmacology methodology, molecular docking studies, ultraperformance liquid chromatography UPLC-Orbitrap-Exploris-120-MS and a severe second-degree burn rat model to investigate the chemical constituents and potential therapeutic mechanisms of the SBS-EF. ResultsIn vitro studies demonstrated the efficacy of SBS-EF in promoting HSF growth and migration. UPLC-Orbitrap-Exploris-120-MS analysis revealed that SBS-EF had ten major constituents, with flavonoids being the predominant compounds, especially catechin, quercetin, and kaempferol derivatives. Network pharmacology and molecular docking analyses indicated that SBS-EF may exert its healing effects by modulating the Wnt/β-catenin signalling pathway. Subsequent in vivo experiments demonstrated that SBS-EF accelerated burn wound healing in rats, increased hydroxyproline expression in skin tissue, facilitated skin structure repair, and enhanced collagen production and organisation over a 21 d period. Additionally, exposure to SBS-EF upregulated WNT3a and β-catenin while downregulating GSK-3β levels in rat skin tissue. ConclusionsThe wound healing properties of SBS-EF were attributed to its ability to enhance HSF growth and migration, increase hydroxyproline levels in the skin, promote collagen accumulation, reduce scarring, and decrease the skin water content. SBS-EF may also provide therapeutic benefits for burns by modulating the Wnt/β-catenin signalling pathway, as evidenced by its effective site and likely mechanism of action in the treatment of burned rats.

High-density culturing of the dermal fibroblast cells on hydrogel-based soft microcarriers for cell therapy application

Dermal fibroblasts play a pivotal role in cell therapy, serving as versatile cells essential for tissue repair and regeneration. Their unique ability to produce extracellular matrix components contributes significantly to the efficacy and success of various cell-based therapies in treating skin-related conditions and wounds. Scaling up the production of dermal fibroblasts poses a challenge due to their limited lifespan in culture and the need to maintain their specialized functions over multiple generations. Bioreactors offer a promising solution by providing controlled environments that optimize cell growth, allowing for higher yields of dermal fibroblasts while preserving their functionality and minimizing the limitations associated with traditional culture methods. To overcome the critical challenges in large-scale cell manufacturing, we fine-tuned the composition of our existing smart microcarrier, Cytogel, and tailored its chemical and physical properties to cultivate dermal fibroblasts. The fibroblast cell attachment rate to the new optimized formulation is more than 90%, followed by 60% thermal detachment efficiency in 1 h. Additionally, cells harvested from Cytogel displayed superior CD90 expression and enhanced collagen production compared to fibroblasts cultured in tissue flasks in both static and dynamic bioreactor cultures. Overall, our developed hydrogel-based microcarriers exhibited significant promise for efficient cell expansion, offering a groundbreaking approach for industrial-scale cell culture for cell therapeutic applications.

Exosomes from adipose-derived stem cells regulate macrophage polarization and accelerate diabetic wound healing via the circ-Rps5/miR-124-3p axis.

Adipose-derived stem cells (ADSCs) hold promising application prospects in the treatment of diabetic wounds, although the underlying mechanisms of repair have not been fully elucidated. This research aimed to elucidate the mechanisms by which ADSCs promote wound healing. Exosomes from ADSCs were isolated and circRps5 level was identified. To investigate the role of circRps5 in the regulation, exosomes from differently treated ADSCs were used. Different exosomes were injected into the edge of the wound in diabetic mice, and the effects on wound healing status, pathology, collagen, cytokines, and macrophage phenotype were assessed. Raw264.7 cells were co-treated with high glucose and exosomes, and then cell phenotype and autophagy were examined in vitro, followed by the evaluation of miR-124-3p's impact on cell phenotype. Exosomes from ADSCs were isolated and identified using nanoparticle tracking analysis and exosome markers. Overexpression of circRps5 accelerated wound healing, reduced inflammatory response, enhanced collagen production, and promoted the M2 transformation of macrophages. In high glucose-induced macrophages, its overexpression also inhibited excessive autophagy. When macrophages overexpressed miR-124-3p, the induction of the M2 phenotype was suppressed. Luciferase reporter assay proved the combination of circRps5 and miR-124-3p. This study identifies that circRps5 carried by ADSC-Exos promotes macrophage M2 polarization through miR-124-3p. These findings provide valuable insights into the mechanism of ADSC-Exos for treating refractory diabetic wounds, laying a solid theoretical groundwork for future clinical development.

Can Human Growth Hormone Accelerate Tendon and Ligament Injury Recovery?

Studies involving human fibroblasts and use of human growth hormone (HGH) administration for injury recovery are limited. It is plausible that if the administration of HGH to human cells increased cellular proliferation and differentiation, then HGH might be able to assist in accelerating recovery from injury. HGH will increase proliferation and differentiation of human tendon and ligament fibroblasts in vitro based on both a single-dose and a sustained-dose model of HGH administration. Basic science cellular study. Human tendon and ligament tissue were harvested from 24 patients. Tissue samples were digested with type I collagenase to isolate the target cell types. HGH was administered directly to isolated cells at doses ranging from 100 pg/mL to 10 µg/mL, either in a single-dose or a sustained-dose model. Proliferation was analyzed at days 4 and 7. Differentiation of ligament and tendon fibroblasts was assessed at day 14. Administration of a single-dose of HGH to both cell types demonstrated similar or inferior cellular proliferation compared with controls after 7 days. For the sustained-dosing model of ligament fibroblasts, only the 100 ng/mL concentration demonstrated at least statistically similar or improved proliferation compared with controls. When examining the 100 ng/mL HGH concentration with larger sample sizes, cellular proliferation was not improved over controls for any cell type for the single- or sustained-dosing models. Proliferation for tendon fibroblasts was either similar or inferior to the control group at all concentrations of HGH. There was no clear dose-response relationship demonstrating enhanced collagen production with administration of HGH to suggest it enhances injury recovery. HGH administered to human tendon and ligament fibroblasts does not appear to positively affect cellular proliferation and differentiation. This study does not support the use of HGH for accelerating recovery from injury.

NAD-Driven Sirtuin Activation by Cordyceps sinensis Extract: Exploring the Adaptogenic Potential to Promote Skin Longevity.

In recent years, there has been increasing interest in utilizing Traditional Chinese Medicine principles and natural bioactive compounds to combat age-related ailments and enhance longevity. A Cordyceps sinensis mycelium hydroethanolic extract (CsEx), which was standardized in cordycepin and adenosine using UHPLC-DAD, was investigated for its adaptogenic properties using in vitro assays and a double-blind, placebo-controlled clinical trial involving 40 subjects. The CsEx demonstrated activity at a concentration of 0.0006%, significantly increasing sirtuin expression (SirT1: +33%, SirT3: +10%, SirT6: +72%, vs. CTR, p < 0.05) and NAD+ synthesis in HaCat cells (+20% vs. CTR, p < 0.001). Moreover, the CsEx boosted ATP production by 68% in skin cells, correlating with higher skin energy values (+52.0% at D28, p < 0.01) in the clinical trial. Additionally, CsEx notably reduced cytosolic reactive oxygen species (ROS) by 30% in HaCaT cells (p < 0.05) and enhanced collagen production both in vitro (+69% vs. CTR, p < 0.01) and in vivo (+10% vs. D0, p < 0.01), confirmed by ultrasound examination. Furthermore, CsEx's stimulation of fibroblasts, coupled with its antioxidant and energizing properties, led to a significant reduction in wrinkles by 28.0% (D28, p < 0.001). This study underscores Cordyceps sinensis hydroethanolic extract's potential in regulating skin cell energy metabolism and positively influencing the mechanisms associated with skin longevity control.

Targeting S100A9 Prevents β-Adrenergic Activation-Induced Cardiac Injury.

Altered cardiac innate immunity is highly associated with the progression of cardiac disease states and heart failure. S100A8/A9 is an important component of damage-associated molecular patterns (DAMPs) that is critically involved in the pathogenesis of heart failure, thus considered a promising target for pharmacological intervention. In the current study, initially, we validated the role of S100A8/A9 in contributing to cardiac injury and heart failure via the overactivation of the β-adrenergic pathway and tested the potential use of paquinimod as a pharmacological intervention of S100A8/A9 activation in preventing cardiac dysfunction, collagen deposition, inflammation, and immune cell infiltration in β-adrenergic overactivation-mediated heart failure. This finding was further confirmed by the cardiomyocyte-specific silencing of S100A9 via the use of the adeno-associated virus (AAV) 9-mediated short hairpin RNA (shRNA) gene silencing system. Most importantly, in the assessment of the underlying cellular mechanism by which activated S100A8/A9 cause aggravated progression of cardiac fibrosis and heart failure, we discovered that the activated S100A8/A9 can promote fibroblast-macrophage interaction, independent of inflammation, which is likely a key mechanism leading to the enhanced collagen production. Our results revealed that targeting S100A9 provides dual beneficial effects, which is not only a strategy to counteract cardiac inflammation but also preclude cardiac fibroblast-macrophage interactions. The findings of this study also indicate that targeting S100A9 could be a promising strategy for addressing cardiac fibrosis, potentially leading to future drug development.

Antioxidant activity of Jeju lava seawater through translocation of Nrf2 in human fibroblast.

Reactive oxygen species (ROS) are associated with various pathological conditions, including atherosclerosis and cancer. Photoaging, mainly caused by UVB-induced ROS, accelerates skin aging and collagen degradation. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates antioxidant enzymes and has demonstrated protective effects against chronic diseases. Jeju lava seawater (JLS), which is rich in minerals, is attracting attention for its health benefits. The current study investigates the antioxidant properties of JLS in human dermal fibroblasts (HDFs). experiments were conducted by culturing HDFs in JLS with different water hardness levels and irradiating UVB. The results show that JLS does not affect HDF viability, especially at high water hardness. JLS treatment enhances collagen production and upregulates Nrf2 and antioxidant enzymes such as NQO1 and HO-1. This mechanism involves the translocation of Nrf2 to the cell nucleus. JLS shows promise as an antioxidant, potentially mitigating the effects of oxidative stress and promoting collagen synthesis.

The Impact of Early Genes and Gene Editing Technology Associated with Clustered Repeats on the Development of Human Body Organs

Early growth response 1 (EGR-1) and homeobox (Hox) proteins play crucial roles in regulating genes within the body, promoting cell renewal, and expediting the wound healing process. Conversely, Clustered Regularly Interspaced Palindromic Re-peats/Associated (CRISPR-Cas) technology is primarily involved in gene editing. However, significant gaps persist in understanding the mechanisms of key genes like EGR-1, CRISPR/Cas, and HOX genes in organ development. Unveiling their mechanisms is crucial for advancing organ development and discovering new therapeutic strategies. This study aims to investigate the roles of EGR-1, CRISPR/Cas, and HOX genes in organ development and growth. The study used CRISPR/Cas to investigate the impact of catalase mutations on organ regeneration. Early embryonic mutants were generated by injecting gRNAs and Cas9 protein into zygotes, followed by tail amputation in larvae. Additionally, the study explored the role of specific Hox genes in axon elongation and Wnt signaling regulation. EGR-1, induced by TGF-β1, enhanced collagen production, underscoring its importance in wound healing. Integration of EGR-1, HOX proteins, and CRISPR-Cas revealed a regulatory complex influencing organ development. The integration of EGR-1, HOX proteins, and CRISPR-Cas revealed a regulatory complex. EGR-1 aids wound healing, HOX proteins influence fetal development and organ formation, and CRISPR-Cas enables precise genome modifications.

Plac8 regulates the fibrogenic ability of cardiac fibroblasts in mice with myocardial infarction

Cardiac fibroblasts (CFs) are of vital importance for post-myocardial infarction (MI) remodeling. This study explored the role of Placenta specific 8 (Plac8) in MI on the basis of single-cell RNA-Seq (scRNA-Seq) data (GSE136088) and micro-array data (GSE153485). Through bioinformatics analysis, Plac8 was finally identified as a key gene related to fibroblasts. In addition, primary CFs of the neonatal mice were isolated, cultured and treated with hypoxia for in vitro cell model construction. Hydroxyproline assay demonstrated enhanced collagen production in hypoxic CFs, and qRT-PCR revealed increased relative contents of type I and type III collagen (Col1a1 and Col3a1). Western blot showed increased protein expression level of α-smooth muscle actin (α-SMA), and transwell assay and wound-healing assay collectively suggested enhanced cell migration. Moreover, Plac8 was found to be upregulated in hypoxic CFs. Then, after transfection with siNC or siPlac8, it was revealed that down-regulating Plac8 protein expression in hypoxic CFs reduced the levels of collagen secretion, the number of activated CFs and the degree of cell migration, indicating the regulation of Plac8 on hypoxic CFs’ transformation into myofibroblasts, cell migration and collagen deposition. Excessive myocardial fibrosis can cause adverse cardiac remodeling, leading to malignant arrhythmia and even heart failure.

Possible benefits of food supplementation or diet in scar management: A scoping review.

The evidence regarding a potential role of food supplementation as an adjunct therapy in scar aftercare is limited. In this scoping review we aim to provide an overview of the possible beneficial role of supplementations in aftercare settings. After formulating the research question and accompanying key words, a comprehensive search for relevant publications was performed using PubMed and Web of Science. Two authors independently identified and checked each study against the inclusion criteria. All data was collected and summarized for further discussion. After screening, 11 studies were included in the qualitative synthesis. Four studies including human subjects showed a promising connection between scar improvement and supplementation of vitamin D, omega-3 fatty-acids or a Solanaceae-free diet and lower omega-6 fatty-acid intake. Most of the studies were performed on in-vitro models. Preliminary evidence confirmed the beneficial role of vitamin D. Curcumin- and quercetin-supplementation were linked to decreased fibroblast proliferation. Vitamin C enhanced collagen production in healthy as well as keloidal dermal fibroblasts. Chitin stimulated cell-proliferation in human fibroblasts and keratinocytes. The findings suggest early potential benefits of additional food supplementation in scar management for scars but provide no clear evidence. To establish guidelines or gather more evidence on food supplementation, studies involving human subjects (in vivo) are essential. The intricacies associated with nutritional studies in vivo present multifaceted challenges. It should be emphasized that substantial additional evidence is required before aspects such as timing and dosage of supplementation could be addressed for clinical application. Aim: This scoping review looks at whether taking food supplements might help with scar care alongside standard scar management following burn injury. Little information is thought to be available on this subject. An up-to-date review of the literature was undertaken to assimilate the body of evidence and determine if a consensus could be drawn.Method: A specific research question was designed and search conducted in scientific databases like PubMed and Web of Science. Two of our team members carefully selected and reviewed each study to determine which studies met the inclusion or exclusion criteria. All studies that met the inclusion criteria were then reviewed and the information collated to enable conclusions to be drawn.Results: Eleven studies met the inclusion criteria and were used to formulate the conclusions drawn. Four studies showed that taking vitamin D, omega-3 fatty acids, a diet without certain vegetables (Solanaceae), and eating less omega-6 fatty acids might help improve scars. It is important to note that most studies (seven out of 11) were carried out in a laboratory and not with real people. These lab studies showed that vitamin D might be helpful. Supplements like curcumin and quercetin seemed to slow down the growth of skin cells like fibroblasts and keratinocytes. Vitamin C aided collagen synthesis, which is important for healthy skin, in both normal and keloid scar cells. Another substance, chitin, was also found to help skin cells and keratinocytes grow better.Conclusion: Our findings point to some early possible benefits of taking extra nutrient supplements for managing scars but do not provide clear evidence. More research is required to enable the development of supplement recommendation and guidelines to be produced. Future research should focus on human trials but do keep in mind that carrying out supplement studies with people is more complicated. The evidence provided by this scoping review is insufficient to recommend the intake of any supplements or the imposition of dietary restrictions for the purpose of managing scars.

Epithelial-to-mesenchymal transition, inflammation, subsequent collagen production, and reduced proteinase expression cooperatively contribute to cyclosporin-A-induced gingival overgrowth development.

Drug-induced gingival overgrowth (DIGO), induced by certain immunosuppressive drugs, antihypertensive agents, and antiepileptic drugs, may contribute to the formation of deeper periodontal pockets and intractableness in periodontitis. To date, multiple factors such as enhanced matrix production, inflammation, and reduced matrix degradation might be involved in the pathogenesis of DIGO. We have previously reported that SPOCK-1, a heparan sulfate proteoglycan, could affect gingival thickening by promoting epithelial-to-mesenchymal transition (EMT) in gingival keratinocytes. However, few studies have investigated whether a combination of these factors enhances the DIGO phenotype in animal models. Therefore, we investigated whether SPOCK-1, periodontal inflammation, and cyclosporin-A (CsA) could cooperatively promote gingival overgrowth. We first confirmed that Spock-1 overexpressing (Spock1-Tg) mice showed significantly thicker gingiva and greater alveolar bone loss than WT mice in response to ligature-induced experimental periodontitis. DIGO was induced by the combination of CsA administration and experimental periodontitis was significantly enhanced in Spock1-Tg mice compared to that in WT mice. Ligature-induced alveolar bone loss in CsA-treated Spock1-Tg mice was also significantly greater than that in CsA-treated WT mice, while being accompanied by an increase in Rankl and Col1a1 levels and a reduction in matrix metalloprotease expression. Lastly, SPOCK-1 promoted RANKL-induced osteoclast differentiation in both human peripheral blood mononuclear cells and murine macrophages, while peritoneal macrophages from Spock1-Tg mice showed less TNFα and IL-1β secretion than WT mice in response to Escherichia coli lipopolysaccharide. These results suggest that EMT, periodontal inflammation, and subsequent enhanced collagen production and reduced proteinase production contribute to CsA-induced DIGO pathogenesis.

CSMP: A Self-Assembled Plant Polysaccharide-Based Hydrofilm for Enhanced Wound Healing.

Wound management remains a critical healthcare issue due to the rising incidence of chronic diseases leading to persistent wounds. Traditional dressings have their limitations, such as potential for further damage during changing and suboptimal healing conditions. Recently, hydrogel-based dressings have gained attention due to their biocompatibility, biodegradability, and ability to fill wounds. Particularly, polysaccharide-based hydrogels have shown potential in various medical applications. This study focuses on the development of a novel hydrofilm wound dressing produced from a blend of chia seed mucilage (CSM) and polyvinyl alcohol (PVA), termed CSMP. While the individual properties of CSM and PVA are well-documented, their combined potential in wound management is largely unexplored. CSMP, coupled with sorbitol and glycerin, and cross-linked using ultraviolet light, results in a flexible, adhesive, and biocompatible hydrofilm demonstrating superior water absorption, moisturizing, and antibacterial properties. This hydrofilm promotes epithelial cell migration, enhanced collagen production, and outperforms existing commercial dressings in animal tests. The innovative CSMP hydrofilm offers a promising, cost-effective approach for improved wound care, bridging existing gaps in dressing performance and preparation simplicity. Future research can unlock further applications of such polysaccharide-based hydrofilm dressings.

Antioxidant, Anti-Inflammatory Effects and Ability to Stimulate Wound Healing of a Common-Plantain Extract in Alginate Gel Formulations.

Our study aimed to investigate the biological effects of a common-plantain (Plantago major L.) extract, encapsulated in alginate, on dermal human fibroblast cultures in vitro, in view of its potential use as a wound healing adjuvant therapy. Common-plantain extracts were obtained by infusion and ultrasound extraction, and their total polyphenolic content and antioxidant capacity were determined by spectrophotometry. The best extract, which was obtained by infusion, was further encapsulated in sodium alginate in two different formulations. Fourier Transform Infrared Spectroscopy (FTIR) was used to demonstrate the existing interactions in the obtained common-plantain extract in the alginate formulations. The encapsulation efficiency was evaluated based on the total polyphenol content. These alginate gel formulations were further used in vitro to determine their biocompatibility and antioxidant and anti-inflammatory effects by spectrophotometry and ELISA, as well as their ability to stimulate fibroblast migration (scratch test assay) at different time points. In addition, the collagen 1 and 3 levels were determined by Western blot analysis. The data showed that the microencapsulated plantain extract formulations induced an antioxidant, anti-inflammatory effect, enhanced collagen production and increased wound closure in the first 8 h of their application. These results are encouraging for the use of this alginate plantain extract formulation as an adjuvant for skin wound healing.

Optimal Changes Seen in Patients After Treatment With Poly- l -Lactic Acid: A Retrospective Descriptive Study.

Poly- l -lactic acid (PLLA) is a biostimulator that enhances collagen production and leads to volume restoration. It became popular because of its improvement of facial wrinkles and long-lasting effect, although the specific visible changes it causes in the facial area are not fully described. To identify and characterize the visible changes resulting from injecting PLLA into the facial area. A list of 678 patients who underwent 2 to 3 treatments with PLLA injections in this center between 2021 and 2022 were retrieved. After 2 rounds of evaluations, 31 independent international evaluators described the 3 main changes they observed in the before-and-after images (taken approximately 7 months after the last injection session) of the 12 patients with the most significant improvement. A total of 1,015 descriptions were received. They were divided into categories based upon similarity. The main detected changes were better contouring and enhancement of the lateral face, a lifting effect and secondary impact on the nasolabial fold, and improvement of skin texture and skin firmness. Poly- l -lactic acid injections were judged to be effective for contouring, lifting, and improving skin texture in the facial area. Further research is needed to validate these results and create an assessment scale for PLLA injections.

Role of some structural features in EPS from microalgae stimulating collagen production by human dermal fibroblasts

ABSTRACTExopolysaccharides (EPS) from the microalgae Porphyridium cruentum, Chrysotila dentata, Pavlova sp., Diacronema sp., Glossomastix sp., Phaeodactylum tricornutum, and Synechococcus sp. were isolated and depolymerized. First, EPS were submitted to a high pressure pre-treatment step, followed by a solid acid-catalyzed hydrolysis step carried out in a batch or recycle fixed-bed reactor, using a strong acidic cation-exchange resin. Twenty-eight different EPS forms were thus obtained. After characterization of their main structural features (weight- and number-averaged molecular weight, polydispersity index, sulfate and uronic acid contents), we investigated the structure–function relationship of their pro-collagen activity. We found that native microalgae EPS were able to inhibit until 27% of human matrix metalloproteinase-1 (MMP-1) activity while the depolymerized forms were able to enhance collagen production by two different human fibroblast lines, used as cell models due to their major role in dermal collagen biosynthesis. The most active EPS forms, obtained by depolymerization in the recycle fixed-bed reactor of D. ennorea and Glossomastix sp. EPS, led to 390% increase in collagen production. Finally, principal component (PCA) and Pearson analyses indicated that MMP-1 inhibition was strongly correlated to the sulfate group content of EPS whereas collagen production by fibroblasts was mostly related to their proportion of low molecular weight polysaccharides (<10 kDa). Uronic acid content of EPS was also shown essential but only if the size of EPS was reduced in the first place. Altogether, these results gave new insights of the dermo-cosmetic potential of microalgae EPS as well as the key parameters of their activity.

Hyaluronic acid/alginate-based biomimetic hydrogel membranes for accelerated diabetic wound repair

The study aims to develop a new multifunctional biopolymer-based hydrogel membrane dressing by adopting a solvent casting method for the controlled release of cefotaxime sodium at the wound site. Sodium alginate enhances collagen production in the skin, which provides tensile strength to healing tissue. Moreover, the significance of extracellular molecules such as hyaluronic acid in the wound the healing cascade renders these biopolymers an essential ingredient for the fabrication of hydrogel membranes via physical crosslinking (hydrogen bonding). These membranes were further investigated in terms of their structure, and surface morphology, as well as cell viability analysis. A membrane with the most suitable characteristics was chosen as a candidate for cefotaxime sodium loading and in vivo analysis. Results show that the 3D porous nature of developed membranes allows optimum water vapor and oxygen transmission (>8.21 mg/mL) to divert excessive wound exudate away from the diabetic wound bed, MTT assay confirmed cell viability at more than 80%. In vivo results confirmed that the CTX-HA-Alg-PVA hydrogel group showed rapid wound healing with accelerated re-epithelization and a decreased inflammatory response. Conclusively, these findings indicate that CTX-HA-Alg-PVA hydrogel membranes exhibit a suitable niche for use as dressing membranes for healing of diabetic wounds.

Primary human osteoblast and mesenchymal stem cell responses to apatite/tricalcium phosphate bone cement modified with polyacrylic acid and bioactive glass.

In this work, three different modified cements, control apatite/beta-tricalcium phosphate cement (CPC), polymeric CPC (p-CPC), and bioactive glass added polymeric cement (p-CPC/BG) were evaluated regarding their physical properties and the responses of primary human osteoblast cells (HObs) and mesenchymal stem cells (MSCs). Although polyacrylic acid (PAA) increased compressive strength and Young's modulus of the cement, it could cause poor apatite phase formation, a prolonged setting time, and a lower degradation rate. Consequently, bioactive glass (BG) was added to PAA/cement to improve its physical properties, such as compressive strength, Young's modulus, setting time, and degradation. For in vitro testing, HObs viability was assessed under two culture systems with cement-preconditioned medium (indirect) and with cement (direct). HObs viability was examined in direct contact with cements treated by different prewashing conditions. HObs presented a more well spread morphology on cement soaked in medium overnight, as compared to other cements with no treatment and washing in PBS. In addition, the proliferation, differentiation, and total collagen production of both HObs and MSCs adhered to the cement were detected. Cells showed excellent proliferation on PAA/cement and PAA/BG/cement. Furthermore, the higher released Si ion and lower acidosis of PAA/BG/cement-conditioned medium resulted in an increase in osteogenic differentiation (HObs and MSCs) and enhanced collagen production (HObs in osteogenic medium and MSCs in control medium). Therefore, our findings suggest that BG incorporated PAA/apatite/β-TCP cement could be a promising formula for bone repair applications.

Fibroblast-targeting polymeric nanovehicles to enhance topical wound healing through promotion of PAR-2 receptor-mediated endocytosis.

The level of collagen production critically determines skin wound contraction. If an intelligent skin drug delivery technology that enables collagen production in a specific wound skin area is developed, a breakthrough in wound healing treatment would be expected. However, such an intelligent drug delivery technology has not yet been developed as much as in the field of anticancer therapy. In this study, we propose a smart drug delivery system using polymeric nanovehicles (PNVs), in which the periphery is conjugated with a fibroblast-targeting collagen-derived peptide, KTTKS (Lys-Thr-Thr-Lys-Ser). We showed that surface engineering of PNVs with simultaneous PEGylation and peptide patching improved the dispersibility of PNVs, while promoting selective cellular uptake to fibroblasts via PAR-2 receptor-mediated endocytosis. In vitro collagen production and in vivo wound healing assays revealed that curcumin-loaded fibroblast-targeting PNVs significantly enhanced collagen production and wound healing activities, thus promising effective skin tissue regeneration.

MicroRNA-29a inhibits collagen expression and induces apoptosis in human fetal scleral fibroblasts by targeting the Hsp47/Smad3 signaling pathway.

Members of the microRNA-29 (miR-29) gene family have been implicated as suppressors of collagen in several human diseases. The present study aimed to explore the function of miR-29a in human fetal scleral fibroblasts (HFSFs) and to investigate potential mechanisms by which the molecule regulates cellular functioning. First, HFSFs were transfected with miR-29a mimic, miR-29a inhibitor, or their corresponding controls. Then, cell proliferation and apoptosis were assessed using a CCK-8 assay and flow cytometry, respectively. Further, using real-time PCR, western blotting, and immunofluorescence staining, levels of miR-29a, heat shock protein 47 (Hsp47), COL1A1, Smad3, P-Smad3, Bax, and Bcl-2 were investigated. Next, empty vectors and SERPINH1-overexpressing vectors were used to transfect HFSFs. Western blotting and flow cytometry were performed to assess changes in levels of HFSF protein expression and apoptosis, respectively. Results indicated that the miR-29a mimic significantly inhibited Hsp47, Smad3, P-Smad3, and COL1A1 expression. Conversely, the miR-29a inhibitor enhanced the expression of the same genes. Furthermore, miR-29a overexpression inhibited HFSFs proliferation and enhanced the rate of HFSFs apoptosis. Consistent with this finding, miR-29a overexpression led to the downregulation of Bcl-2 and upregulation of Bax. In contrast, miR-29a suppression led to the upregulation of Bcl-2 and downregulation of Bax expression and reduced the rate of apoptosis. Additional research revealed that overexpression of Hsp47 prevented HFSFs apoptosis and enhanced collagen production. Findings that miR-29a overexpression reduces collagen expression levels, slows proliferation, and promotes apoptosis in HFSFs highlight the key role of miR-29a in scleral remodeling. The effects of miR-29a on scleral remodeling might mediate by targeting Hsp47 and repressing the Smad3 pathway.