Estimation of cancer cell migration in biomimetic random/oriented collagen fiber microenvironments

Increasing data indicate that cancer cell migration is regulated by extracellular matrixes and their surrounding biochemical microenvironment,playing a crucial role in pathological processes such as tumor invasion and metastasis.However,conventional two-dimensional cell culture and animal models have limitations in studying the influence of tumor microenvironment on cancer cell migration.Fortunately,the further development of microfluidic technology has provided solutions for the study of such questions.We utilize microfluidic chip to build a random collagen fiber microenvironment(RFM)model and an oriented collagen fiber microenvironment(OFM)model that resemble early stage and late stage breast cancer microenvironments,respectively.By combining cell culture,biochemical concentration gradient construction,and microscopic imaging techniques,we investigate the impact of different collagen fiber biochemical microenvironments on the migration of breast cancer MDA-MB-231-RFP cells.The results show that MDA-MB-231-RFP cells migrate further in the OFM model compared to the RFM model,with significant differences observed.Furthermore,we establish concentration gradients of the anticancer drug paclitaxel in both the RFM and OFM models and find that paclitaxel significantly inhibits the migration of MDA-MB-231-RFP cells in the RFM model,with stronger inhibition on the high concentration side compared to the low concentration side.However,the inhibitory effect of paclitaxel on the migration of MDA-MB-231-RFP cells in the OFM model is weak.These findings suggest that the oriented collagen fiber microenvironment resembling the late-stage tumor microenvironment is more favorable for cancer cell migration and that the effectiveness of anticancer drugs is diminished.The RFM and OFM models constructed in this study not only provide a platform for studying the mechanism of cancer development,but also serve as a tool for the initial measurement of drug screening.

Anti-abrasion collagen fiber-based membrane functionalized by UiO-66-NH_(2)with ultra-high efficiency and stability for oil-in-water emulsions separation

Membrane separation strategies offer promising platform for the emulsion separation.However,the low mechanical strength of membrane separation layers and the trade-off between separation flux and efficiency present significant challenges.In this study,we report a CFM@UiO-66-NH_(2)membrane with high separation flux,efficiency and stability,through utilizing a robust anti-abrasion collagen fiber membrane(CFM)as the multifunctional support and UiO-66-NH_(2)by an in-situ growth as the separation layer.The high mechanical strength of the CFM compensated for the weakness of the separation layer,while the charge-breaking effect of UiO-66-NH_(2),along with the size sieving of its constituent separating layers and the capillary effect of the collagen fibers,contributed to the potential for efficient separation.Additionally,the CFM@UiO-66-NH_(2)membrane exhibited superhydrophilic properties,making it suitable for separating oil-in-water microemulsions and nanoemulsions stabilized by anionic surfactants.The membrane demonstrated remarkable separation efficiencies of up to 99.960%and a separation flux of370.05 L·m^(-2)·h^(-1).Moreover,it exhibits stability,durability,and abrasion resistance,maintaining excellent separation performance even when exposed to strong acids and alkalis without any damage to its structure and performance.After six cycles of reuse,it achieved a separation flux of 417.97 L·m^(-2)·h^(-1)and a separation efficiency of 99.747%.Furthermore,after undergoing 500 cycles of strong abrasion,the separation flux remained at 124.39 L·m^(-2)·h^(-1),with a separation efficiency of 99.992%.These properties make it suitable for the long-term use in harsh operating environments.We attribute these properties to the electrostatic effect resulting from the amino group on UiO-66-NH_(2)and its in-situ growth on the CFM,which forms a size-screening separation layer.Our work highlights the potential of the CFM@UiO-66-NH_(2)membrane as an environmentally friendly size-screening material for the efficient emulsion wastewater separation.

Preparation,characterization and antioxidant activity analysis of three Maillard glycosylated bone collagen hydrolysates from chicken,porcine and bovine

Bone collagen hydrolysates(peptides)derived from byproduct of animal product processing have been used to produce commercially valuable products due to their potential antioxidant activity.Maillard glycosylated reaction is considered as a promising method to enhance the antioxidant activity of peptides.Hence,this research aims at investigating the Maillard glycosylation activity and antioxidant activity of bone collagen hydrolysates from different sources.In this study,3 glycosylated bone collagen hydrolysates were prepared and characterized,and cytotoxicity and antioxidant activity were analyzed and evaluated.The free amino groups loss,browning intensity,and fluorescence intensity of G-Cbcp(glycosylated chicken bone collagen hydrolysates(peptides))were the heaviest,followed by G-Pbcp(glycosylated porcine bone collagen hydrolysates(peptides))and G-Bbcp(glycosylated bovine bone collagen hydrolysates(peptides)).The results of amino acid analysis showed that amino acid composition of different bone collagen hydrolysates was significantly different and the amino acid decreased to different degrees after Maillard glycosylated reaction,which may lead to differences in Maillard glycosylated reaction activity.Furthermore,the 3 glycosylated hydrolysates showed no significant cytotoxicity.The results showed that glycosylation process significantly increased the antioxidant activity of bone collagen hydrolysates,and G-Cbcp showed the strongest antioxidant activity,followed by G-Pbcp and G-Bbcp.Therefore,compared with the bone collagen hydrolysates,3 glycosylated hydrolysates showed significant characteristic and structural changes,and higher antioxidant activity.

Corneal collagen cross-linking in patients with keratoconus from the Dresden protocol to customized solutions:theoretical basis

Keratoconus is an ectatic condition characterized by gradual corneal thinning,corneal protrusion,progressive irregular astigmatism,corneal fibrosis,and visual impairment.The therapeutic options regarding improvement of visual function include glasses or soft contact lenses correction for initial stages,gas-permeable rigid contact lenses,scleral lenses,implantation of intrastromal corneal ring or corneal transplants for most advanced stages.In keratoconus cases showing disease progression corneal collagen crosslinking(CXL)has been proven to be an effective,minimally invasive and safe procedure.CXL consists of a photochemical reaction of corneal collagen by riboflavin stimulation with ultraviolet A radiation,resulting in stromal crosslinks formation.The aim of this review is to carry out an examination of CXL methods based on theoretical basis and mathematical models,from the original Dresden protocol to the most recent developments in the technique,reporting the changes proposed in the last 15y and examining the advantages and disadvantages of the various treatment protocols.Finally,the limits of non-standardized methods and the perspectives offered by a customization of the treatment are highlighted.

Calcium-chelating peptides from rabbit bone collagen:characterization,identification and mechanism elucidation

This study aimed to characterize and identify calcium-chelating peptides from rabbit bone collagen and explore the underlying chelating mechanism.Collagen peptides and calcium were extracted from rabbit bone by instant ejection steam explosion(ICSE)combined with enzymatic hydrolysis,followed by chelation reaction to prepare rabbit bone peptide-calcium chelate(RBCP-Ca).The chelating sites were further analyzed by liquid chromatography-tandem mass(LC-MS/MS)spectrometry while the chelating mechanism and binding modes were investigated.The structural characterization revealed that RBCP successfully chelated with calcium ions.Furthermore,LC-MS/MS analysis indicated that the binding sites included both acidic amino acids(Asp and Glu)and basic amino acids(Lys and Arg),Interestingly,three binding modes,namely Inter-Linking,Loop-Linking and Mono-Linking were for the first time found,while Inter-Linking mode accounted for the highest proportion(75.1%),suggesting that chelation of calcium ions frequently occurred between two peptides.Overall,this study provides a theoretical basis for the elucidation of chelation mechanism of calcium-chelating peptides.

Clinical efficacy of intradermal type Ⅰ collagen injections in treating skin photoaging in patients from high-altitude areas

BACKGROUND Photoaging,a result of chronic sun exposure,leads to skin damage and pigmentation changes.Traditional treatments may have limitations in high-altitude areas like Yunnan Province.Intradermal Col Ⅰ injections stimulate collagen production,potentially improving skin quality.This study aims to assess the efficacy and safety of this treatment for photoaging.AIM To evaluate the efficacy and safety of intradermal typeΙcollagen(ColΙ)injection for treating photoaging.METHODS This prospective,self-controlled study investigated the impact of intradermal injections of ColΙon skin photodamage in 20 patients from the Yunnan Province.Total six treatment sessions were conducted every 4 wk±3 d.Before and after each treatment,facial skin characteristics were quantified using a VISIA skin detector.Skin thickness data were assessed using the ultrasound probes of the Dermalab skin detector.The Face-Q scale was used for subjective evaluation of the treatment effect by the patients.RESULTS The skin thickness of the right cheek consistently increased after each treatment session compared with baseline.The skin thickness of the left cheek significantly increased after the third through sixth treatment sessions compared with baseline.The skin thickness of the right zygomatic region increased after the second to sixth treatment sessions,whereas that of the left zygomatic region showed a significant increase after the fourth through sixth treatment sessions.The skin thickness of both temporal regions significantly increased after the fifth and sixth treatment sessions compared with baseline(P<0.05).These findings were also supported by skin ultrasound images.The feature count for the red areas and wrinkle feature count decreased following the treatment(P<0.05).VISIA assessments also revealed a decrease in the red areas after treatment.The Face-QSatisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin scores significantly increased after each treatment session.The overall appearance of the patients improved after treatment.CONCLUSION Intradermal ColΙinjection improves photoaging,with higher patient satisfaction and fewer adverse reactions,and could be an effective treatment method for populations residing in high-altitude areas.

Electroacupuncture improves myocardial fibrosis in heart failure rats by attenuating ECM collagen deposition through modulation of TGF-β1/Smads signaling pathway

Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure treatment. Methods: Healthy male Sprague-Dawley rats were allocated into three groups: Sham group, Model group, and electroacupuncture (Model + EA) group, with each group comprising 8 rats. The model underwent a procedure involving the ligation of the left anterior descending coronary artery to induce a model of heart failure. The Model + EA group was used for 7 consecutive days for electroacupuncture of bilateral Shenmen (HT7) and Tongli (HT5), once a day for 30 min each time. Left ventricular parameters in rats were assessed using a small-animal ultrasound machine to analyze changes in left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. Serum interleukin-1β (IL-1β), cardiac troponin (cTn), and N-terminal brain natriuretic peptide precursor levels were measured using ELISA. Histopathological changes in rat myocardium were observed through HE staining, while collagen deposition in rat myocardial tissue was assessed using the Masson staining method. Picro sirius red staining, immunohistochemical staining, and RT-qPCR were utilized to distinguish between the various types of collagen deposition. The expression level of TGF-β1 and SMAD2/3/4/7 mRNA in rat myocardial tissues was determined using RT-qPCR. Additionally, western blot analysis was conducted to assess the protein expression levels of TGF-β1, SMAD3/7, and p-SMAD3 in rat myocardial tissues. Results: Compared with the Sham group, the left ventricular ejection fraction and left ventricular fractional shortening values of the Model group were significantly decreased (P < 0.01);the left ventricular end-diastolic volume and left ventricular end-systolic volume values were remarkably increased (P < 0.01);serum N-terminal brain natriuretic peptide precursor content was increased (P < 0.01);serum IL-1β and cTn levels were increased (P < 0.01);myocardial collagen volume fraction were increased (P < 0.01);and those of the expression of TGF-β1 and SMAD2/3/4 mRNA was increased (P < 0.01);the expression of SMAD7 mRNA was decreased (P < 0.01);the protein expression levels of TGF-β1, SMAD3, and p-Smad3 were increased (P < 0.01);the protein expression level of SMAD7 was decreased (P < 0.01) in the Model group. Compared to the Model group, the expression levels of the proteins TGF-β1, SMAD3, and p-Smad3 in myocardial tissue were found to be decreased (P < 0.01), and the expression level of the protein SMAD7 was found to be increased (P < 0.01) in the Model + EA group;the collagen volume fraction and deposition of type Ⅰ /Ⅲ collagen were decreased (P < 0.01) in the Model + EA group. Conclusion: Electroacupuncture alleviates myocardial fibrosis in rats with heart failure, and this effect is likely due to attributed to the modulation of the TGF-β1/Smads signaling pathway, which helps reduce collagen deposition in the extracellular matrix.

Tissue Regeneration in Infected Wounds of Albino Rats Using Ciprofloxacin-Loaded Gelatin Microspheres Incorporated Collagen Scaffold: A Histological Approach with H&E Staining

A wound care system consisting of ciprofloxacin-loaded gelatin microspheres impregnated in a macroporous collagen scaffold was created to effectively control wound infection and regenerate soft tissue at the wound site.Histological and biochemical alterations were observed in infected wounds treated with these scaffolds in Albino Wistar rats.Furthermore,the study examined the immediate and prolonged release of ciprofloxacin from the scaffolds,as well as their function in eliminating bacterial infections and expediting the process of skin healing and regeneration.The developed technique was followed in the streamlined process of creating these collagen scaffolds.Compared to untreated wounds,the group receiving scaffold treatment experienced a faster rate of wound closure.It was noted that the rate of infections was considerably reduced and that full soft tissue regeneration occurred within 12 days.The development of well-deposited collagen bundles in the treated groups was demonstrated by H&E staining,which verified the flawless regeneration of the dermis and epidermis.The antimicrobial agent-loaded gelatin microspheres impregnated into the porous collagen scaffold demonstrated remarkable soft tissue regeneration and efficient infection control at the wound site.

Dietary protein levels changed the hardness of muscle by acting on muscle fiber growth and the metabolism of collagen in sub-adult grass carp(Ctenopharyngodon idella)

Background:Nutrient regulation has been proven to be an effective way to improve the flesh quality in fish.As a necessary nutrient for fish growth,protein accounts for the highest proportion in the fish diet and is expensive.Although our team found that the effect of protein on the muscle hardness of grass carp was probably related to an increased collagen content,the mechanism for this effect has not been deeply explored.Moreover,few studies have explored the protein requirements of sub-adult grass crap(Ctenopharyngodon idella).Therefore,the effects of different dietary protein levels on the growth performance,nutritional value,muscle hardness,muscle fiber growth,collagen metabolism and related molecule expression in grass carp were investigated.Methods:A total of 450 healthy grass carp(721.16±1.98 g)were selected and assigned randomly to six experimen-tal groups with three replicates each(n=25/replicate),and were fed six diets with 15.91%,19.39%,22.10%,25.59%,28.53%and 31.42%protein for 60 d.Results:Appropriate levels of dietary protein increased the feed intake,percentage weight gain,specific growth rate,body composition,unsaturated fatty acid content in muscle,partial free amino acid content in muscle,and muscle hardness of grass carp.These protein levels also increased the muscle fiber density,the frequency of new muscle fibers,the contents of collagen and IGF-1,and the enzyme activities of prolyl 4-hydroxylases and lysyloxidase,and decreased the activity of matrix metalloproteinase-2.At the molecular level,the optimal dietary protein increased col-lagen type Iα1(Colα1),Colα2,PI3K,Akt,S6K1,La ribonucleoprotein domain family member 6a(LARP6a),TGF-β1,Smad2,Smad4,Smad3,tissue inhibitor of metalloproteinase-2,MyoD,Myf5,MyoG and MyHC relative mRNA levels.The levels of the myostatin-1 and myostatin-2 genes were downregulated,and the protein expression levels of p-Smad2,Smad2,Smad4,p-Akt,Akt,LARP6 and Smad3 were increased.Conclusions:The appropriate levels of dietary protein promoted the growth of sub-adult grass carp and improved muscle hardness by promoting the growth of muscle fibers,improving collagen synthesis and depressing collagen degradation.In addition,the dietary protein requirements of sub-adult grass carp were 26.21%and 24.85%according to the quadratic regression analysis of growth performance(SGR)and the muscle hardness(collagen content),respectively.

Effect of non-enzymatic glycation on collagen nanoscale mechanisms in diabetic and age-related bone fragility

Age and diabetes have long been known to induce an oxidative reaction between glucose and collagen,leading to the accumulation of advanced glycation end-products(AGEs)cross-links in collagenous tissues.More recently,AGEs content has been related to loss of bone quality,independent of bone mass,and increased fracture risk with aging and diabetes.Loss of bone quality is mostly attributed to changes in material properties,structural organization,or cellular remodeling.Though all these factors play a role in bone fragility disease,some common recurring patterns can be found between diabetic and age-related bone fragility.The main pattern we will discuss in this viewpoint is the increase of fibrillar collagen stiffness and loss of collagen-induced plasticity with AGE accumulation.This study focused on recent related experimental studies and discusses the correlation between fluorescent AGEs content at the molecular and fibrillar scales,collagen deformation mechanisms at the nanoscale,and resistance to bone fracture at the macroscale.

Supplementation with yak (Bos grunniens) bone collagen hydrolysate altered the structure of gut microbiota and elevated short-chain fatty acid production in mice

In this study, yak bone collagen hydrolysate(YBCH)was produced by mixed proteases and provided to standard-diet mice at a different dose(low dose(LD), medium dose(MD), and high dose(HD))to investigate its effects on the composition of gut microbiota and short-chain fatty acids(SCFA)production. It was found that YBCH was mainly composed of small molecular peptides whose molecular weight below 2 000 Da. Notably, supplementation with different doses of YBCH could significantly downregulate the ratio of Firmicutes to Bacteroidetes in the fecal microbiota. At the family level, the Lachnospiraceae abundance was significantly reduced in the YBCH gavage groups(mean reduction ratio 41.7 %, 35.2%, and 36.4% for LD, MD, and HD group, respectively). The predicted functions of gut microbes in the MD group were significantly increased at “lipid metabolism” and “glycan biosynthesis and metabolism”. Moreover, the SCFA production in the YBCH groups was elevated. Especially, the concentration of acetic acid, propionic acid, and butyric acid in the MD group was separately increased 79.7%, 89.2%, and 78.8% than that in the NC group. These results indicated that YBCH might be applied in the development of functional food for intestinal microecological regulation.

Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury

There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are limited.Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury.In this study,we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1(3D-CC-INEXOS) to improve traumatic brain injury repair and functional recove ry after traumatic brain injury in rats.Composite scaffolds comprising collagen,chitosan,and exosomes derived from neural stem cells pretreated with insulin-like growth fa ctor-1(INEXOS) continuously released exosomes for 2weeks.Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model,as assessed by the Morris water maze test and modified neurological seve rity scores.In addition,immunofluorescence staining and transmission electron microscopy showed that3D-CC-INExos implantation significantly improved the recove ry of damaged nerve tissue in the injured area.In conclusion,this study suggests that transplanted3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

Rapid and efficient characterization of cervical collagen orientation using linearly polarized colposcopic images

Collagen provides tissue strength and structural integrity.Quanti fication of the orientated dispersion of collagen fibers is an important factor when studying the mechanical properties of the cervix.In this study,for the first time,a new method for rapid characterization of the collagen fiber orientations of the cervix using linearly polarized light colposcopy is presented.A total of 24 colposcopic images were captured using a cross-polarized imaging system with white LED light sources.In the preprocessing stage,the Red channel of the RGB image was chosen,which contains no information of the blood vessels because of the low-absorption of blood cells in the red region.OrientationJ,which is an ImageJ plug-in,was used to estimate the local orientation of the collagen fibers.The result shows that in the nonpregnant cervix,the middle zone(Zone 2)has circumferentially aligned collagen fibers while the inner zone(Zone 1)has randomly arranged.The collagen fiber dispersion in Zone 2 is much smaller than that in Zone 1 at all four quadrants region(anterior,posterior,left,and right quadrant).This new analysis technique could potentially combine with diagnostic tools to provide a quantitative platform of collagen fibers in the clinic.

Altered Expression of COMP,Collagen 1,and MMP9 in Pelvic Organ Prolapse

Female pelvic organ prolapse(POP)is a common disorder that affects the quality of life of women considerably.Studies in China have reported a 9.6%prevalence of symptomatic POP in adult women[1],with a higher prevalence among older women.

Effect of hydroalcoholic leaf extract of Cassia fistula L.on typeⅡcollagen-induced arthritis in rats

Objective:To explore the effect of Cassia fistula on collagenⅡ-induced arthritis in rats.Methods:The effect of 250 and 500 mg/kg chloroform and hydroalcoholic extract of Cassia fistula leaf on collagenⅡ-induced arthritis was investigated by evaluating paw volume,arthritis index,spleen index,and biochemical parameters.Histopathological analysis and docking study were also performed.Results:A dose-dependent reduction in paw volume,arthritic index,and spleen index was observed following oral administration of the chloroform and hydroalcoholic extracts.Treatment with Cassia fistula extracts reduced tumor necrosis factor-α,interleukin(IL)-1β,IL-6,prostaglandin E_(2),aspartate aminotransferase,alanine aminotransferase,total leucocyte count,and erythrocyte sedimentation rate while increasing IL-10 level.In addition,Cassia fistula extracts improved joint architecture,and prevented cartilage and bone destruction.Docking analysis demonstrated that the physcion,1-octacosanol,5,3’,4’-trihydroxy-6-methoxy-7-O-α-Lrhamnopyranosyl-(1,2)-O-β-D-galactopyranoside and scopoletin may be responsible for the anti-arthritic effect of Cassia fistula.Conclusions:Cassia fistula suppresses the progression of collagenⅡ-induced arthritis by lowering the inflammatory factors,decreasing paw volume and arthritic index,and alleviating joint architecture.However,further studies are required to confirm the bioactive molecule responsible for the anti-arthritic potential of Cassia fistula.

Three-dimensional remodeling of collagen fibers within cervical tissues in pregnancy

The cervix is a collagen-rich connective tissue that must remain closed during pregnancy while undergoing progressive remodeling in preparation for delivery,which begins before the onset of the preterm labor process.Therefore,it is important to resolve the changes of collagen flbers during cervical remodeling for the prevention of preterm labor.Herein,we assessed the spatial organization of collagen flbers in a three-dimensional(3D)context within cervical tissues of mice on day 3,9,12,15 and 18 of gestation.We found that the 3D directional variance,a novel metric of alignment,was higher on day 9 than that on day 3 and then gradually decreased from day 9 to day 18.Compared with two-dimensional(2D)approach,a higher sensitivity was achieved from 3D analysis,highlighting the importance of truly 3D quantification.Moreover,the depthdependent variation of 3D directional variance was investigated.By combining multiple 3D directional variance-derived metrics,a high level of classification accuracy was acquired in distinguishing different periods of pregnancy.These results demonstrate that 3D directional variance is sensitive to remodeling of collagen fibers within cervical tissues,shedding new light on highly-sensitive,early detection of preterm birth(PTB).

Review on marine collagen peptides induce cancer cell apoptosis,necrosis,and autophagy by reducing oxidized free radicals

Marine collagen peptides(MCPs)are natural products prepared by hydrolyzing marine collagen protein through a variety of chemical methods or enzymes.MCPs have a range of structures and biological activities and are widely present in marine species.MCPs also have a small molecular weight,are easily modified,and absorbed by the body.These properties have attracted great interest from researchers studying antioxidant,anti-tumor,and anti-aging activities.MCPs of specific molecular weights have significant anti-tumor activity and no toxic side effects.Thus,MCPs have the potential use as anti-cancer adjuvant drugs.Free radicals produced by oxidation are closely related to human aging,cancer,arteriosclerosis,and other diseases,but their relationship with cancer is not well known.In this review,we focus on the antioxidant properties of MCPs in the treatment of cancer,highlighting their antioxidant molecular structure and potential for clinical practice.

Injectable collagen scaffold with human umbilical cordderived mesenchymal stem cells promotes functional recovery in patients with spontaneous intracerebral hemorrhage:phase Ⅰ clinical trial

Animal expe riments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury.To investigate whether injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can be used to treat spontaneous intracerebral hemorrhage,this non-randomized phase I clinical trial recruited patients who met the inclusion criteria and did not meet the exclusion crite ria of spontaneous intracerebral hemorrhage treated in the Characteristic Medical Center of Chinese People’s Armed Police Force from May 2016 to December 2020.Patients were divided into three groups according to the clinical situation and patient benefit:control(n=18),human umbilical cord-derived mesenchymal stem cells(n=4),and combination(n=8).The control group did not receive any transplantation.The human umbilical cord-derived mesenchymal stem cells group received human umbilical cord-derived mesenchymal stem cell transplantation.The combination group received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells.Patients who received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells had more remarkable improvements in activities of daily living and cognitive function and smaller foci of intra cerebral hemorrhage-related encephalomalacia.Severe adve rse events associated with cell transplantation were not observed.Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells appears to have great potential treating spontaneous intracerebral hemorrhage.

Quantitative analysis of collagen morphology in breast cancer from millimeter scale using multiphoton microscopy

The tumor microenvironment(TME)is now recognized as an important participant of tumor progression.As the most abundant extracellular matrix component in TME,collagen plays an important role in tumor development.The imaging study of collagen morphological feature in TME is of great significance for understanding the state of tumor.Multiphoton microscopy(MPM),based on second harmonic generation(SHG)and two-photon excitation fluorescence(TPEF),can be used to monitor the morphological changes of biological tissues without labeling.In this study,we used MPM for large-scale imaging of early invasive breast cancer from the tumor center to normal tissues far from the tumor.We found that there were signi¯cant di®erences in collagen morphology between breast cancer tumor boundary,near tumor transition region and normal tissues far from the tumor.Furthermore,the morphological feature of eight collagen¯bers was extracted to quantify the variation trend of collagen in three regions.These results may provide a new perspective for the optimal negative margin width of breast-conserving surgery and the understanding of tumor metastasis.

Collagen matrix scaffolds:Future perspectives for the management of chronic liver diseases

Approximately 1.5 billion chronic liver disease(CLD)cases have been estimated worldwide,encompassing a wide range of liver damage severities.Moreover,liver disease causes approximately 1.75 million deaths per year.CLD is typically characterized by the silent and progressive deterioration of liver parenchyma due to an incessant inflammatory process,cell death,over deposition of extracellular matrix proteins,and dysregulated regeneration.Overall,these processes impair the correct function of this vital organ.Cirrhosis and liver cancer are the main complications of CLD,which accounts for 3.5%of all deaths worldwide.Liver transplantation is the optimal therapeutic option for advanced liver damage.The liver is one of the most common organs transplanted;however,only 10%of liver transplants are successful.In this context,regenerative medicine has made significant progress in the design of biomaterials,such as collagen matrix scaffolds,to address the limitations of organ transplantation(e.g.,low donation rates and biocompatibility).Thus,it remains crucial to continue with experimental and clinical studies to validate the use of collagen matrix scaffolds in liver disease.