Collagen Fragments Research Articles

Phase separation drives the folding of recombinant collagen

Recombinantly produced collagens present a sustainable, ethical, and safe substitute for collagens derived from natural sources. However, controlling the folding of the recombinant collagens, crucial for replicating the mechanical properties of natural materials, remains a formidable task. Collagen-like proteins from willow sawfly are relatively small and contain no hydroxyprolines, presenting an attractive alternative to the large and post-translationally modified mammalian collagens. Utilizing CD spectroscopy and analytical ultracentrifugation, we demonstrate that recombinant willow sawfly collagen assembles into collagen triple helices in a concentration-dependent manner. Interestingly, we observed that the lower concentration threshold for the folding can be overcome by freezing or adding crowding agents. Microscopy data show that both freezing and the addition of crowding agents induce phase separation. We propose that the increase in local protein concentration during phase separation drives the nucleation-step of collagen folding. Finally, we show that freezing also induces the folding of recombinant human collagen fragments and accelerates the folding of natural bovine collagen, indicating the potential to apply phase separation as a universal mechanism to control the folding of recombinant collagens. We anticipate that the results provide a method to induce the nucleation of collagen folding without any requirements for genetic engineering or crosslinking.

Urinary proteomic signature of mineralocorticoid receptor antagonism by spironolactone: evidence from the HOMAGE trial

Abstract Background Heart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) detects many sequenced peptides, for >70% derived from collagens. Purpose UPP and serum fibrosis markers were analysed together in patients at risk of HF with as objective to generate insights into the antifibrotic action of spironolactone. Methods In the open-label HOMAGE trial, patients were randomised to usual therapy combined or not with spironolactone 25-50 mg/d and followed for 9 months (n=290; 23.8% women; median age: 73 years). UPP was done by capillary electrophoresis coupled with mass spectrometry; 1498 urinary peptides with detectable signal in ≥30% of patients were analysed. Serum markers of COL1A1 synthesis (PICP and PICP/CITP) were measured. After rank normalisation of the biomarker distributions, between-group differences in their changes were assessed by multivariable-adjusted models. Correlations between the changes in urinary peptides and in serum PICP and PICP/CITP were compared between groups using Fisher Z transform. Results Among all the urinary peptides, only the changes in collagen fragments remained significantly different (p<0.05) between randomisation groups after accounting for baseline levels, covariables and multiple testing. Compared to the control group, spironolactone reduced 16 of 27 collagen-derived urinary peptides. From baseline to 9 months, serum PICP and the PICP/CITP ratio decreased from 79.0 to 75.4 µg/L and from 21.3 to 18.3, respectively (p≤0.0129), reflecting decreased COL1A1 synthesis. Spironolactone did not affect the correlations between changes in urinary COL1A1 fragments and the serum fibrosis markers. Conclusions Spironolactone downregulated urinary collagen-derived peptides, probably by shrinking the body-wide pool of collagens. Spironolactone did not affect the interaction between urinary and serum fibrosis markers, suggesting that collagen scaffolding is maintained, thereby explaining why some urinary collagen fragments increased. Combining urinary and serum fibrosis biomarkers opens new avenues for discovery of antifibrotic drugs and refines insight in the action of antifibrotic drugs.Figure 1Figure 2

Aging by autodigestion.

The mechanism that triggers the progressive dysregulation of cell functions, inflammation, and breakdown of tissues during aging is currently unknown. We propose here a previously unknown mechanism due to tissue autodigestion by the digestive enzymes. After synthesis in the pancreas, these powerful enzymes are activated and transported inside the lumen of the small intestine to which they are compartmentalized by the mucin/epithelial barrier. We hypothesize that this barrier leaks active digestive enzymes (e.g. during meals) and leads to their accumulation in tissues outside the gastrointestinal tract. Using immune-histochemistry we provide evidence in young (4 months) and old (24 months) rats for significant accumulation of pancreatic trypsin, elastase, lipase, and amylase in peripheral organs, including liver, lung, heart, kidney, brain, and skin. The mucin layer density on the small intestine barrier is attenuated in the old and trypsin leaks across the tip region of intestinal villi with depleted mucin. The accumulation of digestive enzymes is accompanied in the same tissues of the old by damage to collagen, as detected with collagen fragment hybridizing peptides. We provide evidence that the hyperglycemia in the old is accompanied by proteolytic cleavage of the extracellular domain of the insulin receptor. Blockade of pancreatic trypsin in the old by a two-week oral treatment with a serine protease inhibitor (tranexamic acid) serves to significantly reduce trypsin accumulation in organs outside the intestine, collagen damage, as well as hyperglycemia and insulin receptor cleavage. These results support the hypothesis that the breakdown of tissues in aging is due to autodigestion and a side-effect of the fundamental requirement for digestion.

Orthosilicic acid inhibits human osteoclast differentiation and bone resorption.

Silicon (Si), which is present in the diet in the bioavailable form of orthosilicic acid (OSA) and is detected as a dissolution product of certain bone-substitute materials, is suggested to promote bone health, and enhance bone healing, respectively. Silicon has been shown to stimulate osteoblastic cell differentiation and function, although the effect of Si on human osteoclasts is unclear. The present study investigated the direct effects of Si on human osteoclast differentiation, gene expression, and bone resorption. Human CD14+ monocytes were isolated from buffy coats and cultured with M-CSF and RANKL in medium without or with Si (50 μg/ml; constituting 75% OSA). The effects of Si on osteoclast differentiation were evaluated by TRAP-staining and the expression levels of CtsK, CalcR, TRAP, and DC-STAMP measured by RT-qPCR. The effect of Si on the expression level of AQP9, which encodes a potential Si transporter, was also analyzed. Bone resorption was determined based on the number of resorption pits formed when the RANKL-stimulated monocytes were cultured on bone slices, and by the levels of type I collagen fragments released into the cell culture medium. Silicon significantly inhibited the number of TRAP+ multinucleated cells and the expression of osteoclast related genes but increased the late expression of AQP9. Furthermore, Si significantly inhibited the number of resorption pits and the amount of collagen fragments in the medium when cells were cultured on bone slices. Our results demonstrate that OSA inhibits RANKL-stimulated human osteoclast differentiation, gene expression of osteoclast phenotypic markers, and bone resorption.

Correction of Infraorbital Dark Circles Using Autologous Adipose-Derived Collagen Filler: A Novel Regenerative Option.

Numerous intrinsic and extrinsic factors, notably the aging process, contribute to the development of infraorbital dark circles. These features, commonly associated with old age and fatigue, are caused by a disruption of dermal melanin and impairment of skin barrier function. Common aesthetic concerns affecting patients with infraorbital dark circles are primarily owing to lean and translucent lower eyelid skin overlying the orbicularis oculi muscle. This study aimed to present a novel technique for correcting infraorbital dark circles utilizing an adipose-derived extracellular matrix concentrate-adipose collagen fragment (ACF)-to correct infraorbital dark circles. Female patients (n = 94) aged 20-38 who presented infraorbital dark circles were enrolled to assess the efficacy of this technique for an eight-month follow-up. Following intradermal injections with ACF filler, the clinical outcome was determined by responses to GAIS and patient satisfaction surveys. Statistical analysis was performed with the one-way ANOVA test, and a p value of < 0.05 was considered statistically significant. Patients (n = 92) completed a single treatment session and underwent an eight-month follow-up. Eighty patients (86%) reported being "highly satisfied" or "satisfied" with the outcome and responded that the technique resulted in brighter, tighter, and smoother infraorbital skin. Over 97% of patients were rated as "improved," "much improved" and "Very much improved" throughout the follow-up on GAIS by three independent surgeons (p < 0.05). The statistical analyses demonstrated the percentage differences among groups are highly significant (p < 0.0001). No irregularity or lump was observed during the follow-up. Two patients were excluded from the study due to having undergone cosmetic eyelid surgery. Intradermal ACF filler represents a novel approach to addressing infraorbital dark circles and yields significantly high patient satisfaction. ACF fillers provide a degree of bio-stimulation, and adipose-derived concentrate is a natural filler with regenerative effects used in periorbital rejuvenation. 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 .

Comparative analysis of the physical and chemical properties of dried products "KalmaKS" from the skin of the Commander and Pacific squid

The modern system of high-quality nutrition for the population includes the use of natural compounds from secondary products of animal origin. In the course of scientific substantiation of using secondary products from the processing of cephalopods, dried products from the skin of Pacific (Todarodes pacificus) and Commander squid (Berryteuthis magister) have been studied, their protein and amino acid composition and functional and technological characteristics have been analyzed. In samples from the skin of the Pacific squid, a high content of glutamic and aspartic acids (8–10 %) is noted; in samples from the skin of the Commander squid – glycine (20 %), proline (10 %) and arginine. High indicators of solubility, water-holding capacity and stability of foam structures are due to the significant content of type I destructured collagen (in a sample from the skin of Commander squid), and hydrophilic amino acids and type III collagen fragments (in a product made from Pacific squid skin). Infrared drying of products promotes denaturation and gelatinization of collagen in the skin of Commander squid, which is confirmed by the brighter color characteristics of the samples and high moisture-binding capacity when the temperature rises to 40 and 60 °C; this fact indicates an increase in the hydrophilic properties of the products of destruction of collagen fractions. Products made from skin, which is a secondary product of squid processing, have high potential for use in the food industry as water-retaining, fat-binding, and fat-emulsifying components.

Urinary proteomic signature of mineralocorticoid receptor antagonism by spironolactone: evidence from the HOMAGE trial

ObjectiveHeart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70% derived from collagens. This study aimed to refine...

Plasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts

IntroductionThe pathogenesis of sarcoidosis involves tissue remodelling mediated by the accumulation of abnormal extracellular matrix, which is partly the result of an imbalance in collagen synthesis, cross-linking and degradation. During...

Airway extracellular LTA4H concentrations are governed by release from liver hepatocytes and changes in lung vascular permeability

Leukotriene A4 hydrolase (LTA4H) is a bifunctional enzyme, with dual activities critical in defining the scale of tissue inflammation and pathology. LTA4H classically operates intracellularly, primarily within myeloid cells, to generate pro-inflammatory leukotriene B4. However, LTA4H also operates extracellularly to degrade the bioactive collagen fragment proline-glycine-proline to limit neutrophilic inflammation and pathological tissue remodeling. While the dichotomous functions of LTA4H are dictated by location, the cellular source of extracellular enzyme remains unknown. We demonstrate that airway extracellular LTA4H concentrations are governed by the level of pulmonary vascular permeability and influx of an abundant repository of blood-borne enzyme. In turn, blood LTA4H originates from liver hepatocytes, being released constitutively but further upregulated during an acute phase response. These findings have implications for our understanding of how inflammation and repair are regulated and how perturbations to the LTA4H axis may manifest in pathologies of chronic diseases.

Type XII collagen is elevated in serum from patients with solid tumors: a non-invasive biomarker of activated fibroblasts

Understanding the tumor microenvironment (TME) and extracellular matrix (ECM) is crucial in cancer research due to their impact on tumor progression. Collagens, major ECM components, regulate cell signaling and behavior. Of the 28 reported collagens, type XII collagen is known to be vital for ECM organization. Over-produced by cancer-associated fibroblasts (CAFs), its upregulation correlates with poor survival in various cancers. This study aimed to develop an ELISA for quantifying circulating type XII collagen as a cancer biomarker. A specific ELISA targeting the C-terminal of type XII collagen was developed and used to analyze serum samples from cancer patients (n = 203) and healthy controls (n = 33). Additionally, type XII collagen expression was assessed in CAFs and normal fibroblasts (NFs) from different tissues, both under TGF-β stimulated and non-stimulated conditions. The nordicPRO-C12 ELISA demonstrated robustness and specificity for type XII collagen. PRO-C12 levels were significantly elevated in patients with various cancers compared to healthy controls and effectively distinguished between cancer patients and controls. Findings were validated using gene expression data. Furthermore, Western blot analysis revealed increased type XII collagen expression in both CAFs and NFs upon TGF-β1 stimulation, suggesting a potential role of TGF-β1 in modulating the expression of type XII collagen in cancerous and normal tissue microenvironments. This study unveils a promising avenue for harnessing PRO-C12 as a non-invasive serum biomarker, enabling the quantification of type XII collagen fragments in cancer patients. Further investigations are warranted to explore the potential of PRO-C12 across different cancer types and disease stages, shedding light on its multifaceted role in cancer development.

From Biomechanical Properties to Morphological Variations: Exploring the Interplay between Aortic Valve Cuspidity and Ascending Aortic Aneurysm.

Background: This research explores the biomechanical and structural characteristics of ascending thoracic aortic aneurysms (ATAAs), focusing on the differences between bicuspid aortic valve aneurysms (BAV-As) and tricuspid aortic valve aneurysms (TAV-As) with non-dilated aortas to identify specific traits of ATAAs. Methods: Clinical characteristics, laboratory indices, and imaging data from 26 adult patients operated on for aneurysms (BAV-A: n = 12; TAV-A: n = 14) and 13 controls were analyzed. Biomechanical parameters (maximal aortic diameter, strain, and stress) and structural analyses (collagen fiber organization, density, fragmentation, adipocyte deposits, and immune cell infiltration) were assessed. Results: Significant differences in biomechanical parameters were observed. Median maximal strain was 40.0% (control), 63.4% (BAV-A), and 45.3% (TAV-A); median maximal stress was 0.59 MPa (control), 0.78 MPa (BAV-A), and 0.48 MPa (TAV-A). BAV-A showed higher tangential modulus and smaller diameter, with substantial collagen fragmentation (p < 0.001 vs. TAV and controls). TAV-A exhibited increased collagen density (p = 0.025), thickening between media and adventitia layers, and disorganized fibers (p = 0.036). BAV-A patients had elevated adipocyte deposits and immune cell infiltration. Conclusions: This study highlights distinct pathological profiles associated with different valve anatomies. BAV-A is characterized by smaller diameters, higher biomechanical stress, and significant collagen deterioration, underscoring the necessity for tailored clinical strategies for effective management of thoracic aortic aneurysm.

Allicin and Probiotics: Double-edged sword for the management of Striae distensae

Striae distensae (SD), commonly known as Stretch marks or striae, are one of the most common benign dermal lesions frequently seen in females that often cause a significant physical and psychological impact. A number of treatment modalities ranging from topicals to invasive approaches are commercially available, however, none of the available options is capable of complete eradication of SD. As effectiveness of most of the available topical formulations for SD is attributed to the combined effects of their antioxidant, anti-inflammatory and proliferative effects, allicin and probiotic based topical formulations are hypothesized to be effective in treatment and prevention of SD. Both allicin and probiotics are able to reduce the inflammatory response via suppression of transcription factor i.e., nuclear factor (NF)-κB, and pro-inflammatory cytokines and chemokines levels. Moreover, the antioxidant effect of allicin and probiotics is considered to decrease the reactive oxygen species induced fragmentation of collagen. Also, the effects of allicin on the collagen and elastin tissue as well as beneficial effects of probiotics and their metabolites on skin elasticity and skin hydration are expected to provide multiple target approach for the management of SD. Altogether, a combination formulation containing both allicin and probiotics is considered to be novel approach for the prevention and management of SD.

Identification of a human type XVII collagen fragment with high capacity for maintaining skin health

Collagen XVII (COL17) is a transmembrane protein that mediates skin homeostasis. Due to expression of full length collagen was hard to achieve in microorganisms, arising the needs for selection of collagen fragments with desired functions for microbial biosynthesis. Here, COL17 fragments (27–33 amino acids) were extracted and replicated 16 times for recombinant expression in Escherichia coli. Five variants were soluble expressed, with the highest yield of 223 mg/L. The fusion tag was removed for biochemical and biophysical characterization. Circular dichroism results suggested one variant (sample-1707) with a triple-helix structure at >37 °C. Sample-1707 can assemble into nanofiber (width, 5.6 nm) and form hydrogel at 3 mg/mL. Sample-1707 was shown to induce blood clotting and promote osteoblast differentiation. Furthermore, sample-1707 exhibited high capacity to induce mouse hair follicle stem cells differentiation and osteoblast migration, demonstrating a high capacity to induce skin cell regeneration and promote wound healing. A strong hydrogel was prepared from a chitosan and sample-1707 complex with a swelling rate of >30 % higher than simply using chitosan. Fed-batch fermentation of sample-1707 with a 5-L bioreactor obtained a yield of 600 mg/L. These results support the large-scale production of sample-1707 as a biomaterial for use in the skin care industry.

Detection of type I collagen fragments in the gingival crevicular fluid and saliva during orthodontic tooth movement

Detection of type I collagen fragments in the gingival crevicular fluid and saliva during orthodontic tooth movement

From Collagen Mimetics to Collagen Hybridization and Back.

ConspectusFacilitated by the unique triple-helical protein structure, fibrous collagens, the principal proteins in animals, demonstrate a dual function of serving as building blocks for tissue scaffolds and as a bioactive material capable of swift renewal in response to environmental changes. While studies of triple-helical collagen mimetic peptides (CMPs) have been instrumental in understanding the molecular forces responsible for the folding and assembly of triple helices, as well as identifying bioactive regions of fibrous collagen molecules, single-strand CMPs that can specifically target and hybridize to denatured collagens (i.e., collagen hybridizing peptides, CHPs) have proven useful in identifying the remodeling activity of collagen-rich tissues related to development, homeostasis, and pathology. Efforts to improve the utility of CHPs have resulted in the development of new skeletal structures, such as dimeric and cyclic CHPs, as well as the incorporation of artificial amino acids, including fluorinated proline and N-substituted glycines (peptoid residues). In particular, dimeric CHPs were used to capture collagen fragments from biological fluid for biomarker study, and the introduction of peptoid-based collagen mimetics has sparked renewed interest in peptidomimetic research because peptoids enable a stable triple-helical structure and the presentation of an extensive array of side chain structures offering a versatile platform for the development of new collagen mimetics.This Account will cover the evolution of our research from CMPs as biomaterials to ongoing efforts in developing triple-helical peptides with practical theranostic potential in targeting denatured and damaged collagens. Our early efforts in functionalizing natural collagen scaffolds via noncovalent modifications led to the discovery of an entirely new use of CMPs. This discovery resulted in the development of CHPs that are now used by many different laboratories for the investigation of pathologies associated with changes in the structures of extracellular matrices including fibrosis, cancer, and mechanical damage to collagen-rich, load-bearing tissues. Here, we delve into the essential design features of CHPs contributing to their collagen binding properties and practical usage and explore the necessity for further mechanistic understanding of not only the binding processes (e.g., binding domain and stoichiometry of the hybridized complex) but also the biology of collagen degradation, from proteolytic digestion of fibrils to cellular processing of collagen fragments. We also discuss the strengths and weaknesses of peptoid-based triple-helical peptides as applied to collagen hybridization touching on thermodynamic and kinetic aspects of triple-helical folding. Finally, we highlight current limitations and future directions in the use of peptoid building blocks to develop bioactive collagen mimetics as new functional biomaterials.

Collagen peptides affect collagen synthesis and the expression of collagen, elastin, and versican genes in cultured human dermal fibroblasts.

Collagen is one of the major proteins of the skin and it is particularly important for its strength and resilience. Skin aging is a natural process that is characterized by the decrease and fragmentation of collagen in the dermis. Oral supplementation with collagen peptides has been clinically shown to have a positive effect on the skin condition. However, the mechanisms of aging-related changes synthesized by cells exposed to collagen are currently not well understood. Therefore, in this in vitro study, the mechanisms associated with collagen, elastin, and versican in human dermal fibroblasts were investigated after exposure to collagen peptides. The effects of different concentrations of collagen peptides on cell viability and metabolism were analyzed. For gene expression analysis, human dermal fibroblasts were treated with collagen peptides. This was then followed by RNA extraction and DNA synthesis. Gene expressions of collagen type 1 (COL1A1), elastin (ELN), and versican (VCAN) were quantified by quantitative reverse transcription polymerase chain reaction (RT-qPCR). In addition, collagen levels were analyzed by confocal scanning laser microscopy using immunostaining. Collagen peptides tested in the study increased the expression of the relevant COL1A1, ELN, and VCAN genes in human dermal fibroblasts (p < 0.005). Furthermore, confocal microscopy showed increased collagen expression in the dermal fibroblast culture after treatment with the collagen peptides (p < 0.005). These data provide cell-based evidence for the beneficial effects of exposure to collagen peptides on the skin's collagen content and on the molecules that provide firmness and elasticity. This may support the hypothesis that collagen peptides are important for maintaining extracellular matrix (ECM) structure and skin regeneration.

Circadian Regulation of Bone Remodeling.

Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided molecular evidence that bone remodeling is under the control of circadian rhythms. Circadian fluctuations have been reported in the serum and urine levels of bone turnover markers, such as digested collagen fragments and bone alkaline phosphatase. Additionally, the expressions of over a quarter of all transcripts in bones show circadian rhythmicity, including the genes encoding master transcription factors for osteoblastogenesis and osteoclastogenesis, osteogenic cytokines, and signaling pathway proteins. Serum levels of calcium, phosphate, parathyroid hormone, and calcitonin also display circadian rhythmicity. Finally, osteoblast- and osteoclast-specific knockout mice targeting the core circadian regulator gene Bmal1 show disrupted bone remodeling, although the results have not always been consistent. Despite these studies, however, establishing a direct link between circadian rhythms and bone remodeling in vivo remains a major challenge. It is nearly impossible to repeatedly collect bone materials from human subjects while following circadian changes. In addition, the differences in circadian gene regulation between diurnal humans and nocturnal mice, the main model organism, remain unclear. Filling the knowledge gap in the circadian regulation of bone remodeling could reveal novel regulatory mechanisms underlying many bone disorders including osteoporosis, genetic diseases, and fracture healing. This is also an important question for the basic understanding of how cell differentiation progresses under the influence of cyclically fluctuating environments.

Histological Changes of Porcine Animal Skin with Micro-focused Ultrasound.

As a noninvasive alternative therapy, microfocused ultrasound (MFU) has become a research hotspot in recent years for its potential to enhance skin laxity. While several clinical studies have explored the effects of MFU on improving skin laxity, there is limited literature available on the histological changes resulting from MFU treatments. It has been established that the skin structure and composition of the Bama miniature pigs closely resembles that of humans, including collagen content, type I collagen distribution, and elastin distribution. This study primarily focuses on examining the histological alterations in the skin tissue of Bama miniature pigs following MFU application. We also selected some typical clinical photographs of patients treated with MFU and compared the clinical effects with histological changes observed in porcine skin. The MFU device utilized in this study incorporates ultra-pulse technology and large focal area technology. Following the standard operating procedures provided by the manufacturer, different handles were used in different skin area of pigs. Biopsies were obtained immediately after treatment and 1 month after treatment. Significant histological changes were observed in the Bama miniature pigs skin, including collagen contraction and fragmentation, dilation and congestion of superficial dermal capillaries immediately after MFU treatment; dermal thickening, increased thickness and density of collagen fibers, elevated levels of elastin and type I collagen, as well as thickened fiber septa in the adipose layer 1 month later. These histological results corresponded to clinical findings in human, such as facial redness and swelling immediately after treatment, and improvement in facial relaxation after approximately 1 month after treatment. Collectively, these histological findings provide valuable evidence supporting the clinical application of MFU for enhancing skin laxity. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Cell Senescence-Independent Changes of Human Skin Fibroblasts with Age.

Skin ageing is defined, in part, by collagen depletion and fragmentation that leads to a loss of mechanical tension. This is currently believed to reflect, in part, the accumulation of senescent cells. We compared the expression of genes and proteins for components of the extracellular matrix (ECM) as well as their regulators and found that in vitro senescent cells produced more matrix metalloproteinases (MMPs) than proliferating cells from adult and neonatal donors. This was consistent with previous reports of senescent cells contributing to increased matrix degradation with age; however, cells from adult donors proved significantly less capable of producing new collagen than neonatal or senescent cells, and they showed significantly lower myofibroblast activation as determined by the marker α-SMA. Functionally, adult cells also showed slower migration than neonatal cells. We concluded that the increased collagen degradation of aged fibroblasts might reflect senescence, the reduced collagen production likely reflects senescence-independent processes.

Bioactive polyethylene-coated nonwovens for wound healing application

Bioactive non-woven dressings can be prepared by dip coating of non-woven cloth in solutions containing bioactive polyethylene bearing pendant arms of polyethylene (PE5000) and modified PEG3400-biomolecules including linear Arg-Gly-Asp (RGD), collagen fragment (Gly-Pro-Hyp)3, laminin-derived peptide (AGQWHRVSVRWGC) (A5G81) and hyaluronic acid (HA). Obtainment of ultimate coating concentration for each type of non-woven cloth is achieved such that the technically demanding bioactive polyethylene does not delaminate from the non-woven cloth itself but is of sufficient quantity for bioactivity. Scanning electron microscopy images show uniform polyethylene deposition on the non-woven cloth. Good water absorption and permeability allow the use of such bioactive polyethylene coated non-woven cloth as wound dressings. Material biocompatibility is demonstrated using in vitro human skin fibroblast assays. In vivo porcine full thickness excisional wound model shows PE5000-coated non-woven cloth can remarkably accelerate skin regeneration to close the wounds faster than clinical gold standard dressing. Thus, the results presented here may provide a promising guide for bioactive polyethylene-modified non-woven materials for wound dressing applications.