Cellulose fibers-reinforced self-expanding porous composite with multiple hemostatic efficacy and shape adaptability for uncontrollable massive hemorrhage treatment

Uncontrollable hemorrhage leads to high mortality and thus effective bleeding control becomes increasingly important in the military field and civilian trauma arena.However,current hemostats not only present limitation when treating major bleeding,but also have various side effects.Here we report a self-expanding porous composites(CMCP)based on novel carboxymethyl cellulose(CMC)fibers and acetalized polyvinyl alcohol(PVA)for lethal hemorrhage control.The CMC fibers with uniform fibrous structure,high liquid absorption and procoagulant ability,are evenly interspersed inside the composite matrix.The obtained composites possess unique fiber-porous network,excellent absorption capacity,fast liquid-triggered self-expanding ability and robust fatigue resistance,and their physicochemical performance can be fine-tuned through varying the CMC content.In vitro tests show that the porous composite exhibits strong blood clotting ability,high adhesion to blood cells and protein,and the ability to activate platelet and the coagulation system.In vivo hemostatic evaluation further confirms that the CMCP presents high hemostatic efficacy and multiple hemostatic effects in swine femoral artery major hemorrhage model.Additionally,the CMCP will not fall off from the injury site,and is also easy to surgically remove from the wound cavity after the hemostasis.Importantly,results of CT tomography and 3D reconstruction indicate that CMCP can achieve shape adaptation to the surrounding tissues and the wound cavities with different depths and shapes,to accelerate hemostasis while protecting wound tissue and preventing infection.

Stiffness-mediated mesenchymal stem cell fate decision in 3D-bioprinted hydrogels

Background:Hydrogels with tuneable mechanical properties are an attractive material platform for 3D bioprinting.Thus far,numerous studies have confirmed that the biophysical cues of hydrogels,such as stiffness,are known to have a profound impact on mesenchymal stem cell(MSC)differentiation;however,their differentiation potential within 3D-bioprinted hydrogels is not completely understood.Here,we propose a protocol for the exploration of how the stiffness of alginate–gelatin(Alg-Gel)composite hydrogels(the widely used bioink)affects the differentiation of MSCs in the presence or absence of differentiation inducing factors.Methods:Two types of Alg-Gel composite hydrogels(Young’s modulus:50 kPa vs.225 kPa)were bioprinted independently of porosity.Then,stiffness-induced biases towards adipogenic and osteogenic differentiation of the embedded MSCs were analysed by co-staining with alkaline phosphatase(ALP)and oil red O.The expression of specific markers at the gene level was detected after a 3-day culture.Results:Confocal microscopy indicated that all tested hydrogels supported MSC growth and viability during the culture period.Higher expression of adipogenic and osteogenic markers(ALP and lipoprotein lipase(LPL))in stiffer 3D-bioprinted matrices demonstrated a more significant response of MSCs to stiffer hydrogels with respect to differentiation,which was more robust in differentiation-inducing medium.However,the LPL expression in stiffer 3D-bioprinted constructs was reduced at day 3 regardless of the presence of differentiation-inducing factors.Although MSCs embedded in softer hydrogels to some extent proceeded toward adipogenic and osteogenic lineages within a few days,their differentiation seemed to be slower and more limited.Interestingly,the hydrogel itself(without differentiation-inducing factors)exhibited a slight effect on whether MSCs differentiated towards an adipogenic or an osteogenic fate.Considering that the mechanoregulated protein Yes-associated protein(YAP)is involved in MSC fate decisions,we further found that inhibition of YAP significantly downregulated the expression of ALP and LPL in MSCs in stiffer constructs regardless of the induced growth factors present.Conclusions:These results demonstrate that the differentiation of MSCs in 3D-bioprinted matrices is dependent on hydrogel stiffness,which emphasizes the importance of biophysical cues as a determinant of cellular behaviour.

Epidemiology and clinical characteristics of burns in China's Mainland from 2009 to 2018

Background:Burn injuries place a heavy burden on the global healthcare system.However,there is still a lack of nationwide studies on the epidemiological characteristics of burn patients in China's Mainland.The present study aims to accurately analyze the clinical characteristics of burn patients by collecting data in China's Mainland from 2009 to 2018,which will provide effective strategies for healthcare systems and the government in China's Mainland.Methods:Patients admitted for burn injuries to 196 hospitals in 31 provinces,autonomous regions and municipalities in China's Mainland from 2009 to 2018 were included.The data collected included sex,age,month distribution,etiology,region,clinical outcome,injury anatomical location,total burn surface area and mortality.SPSS 19.0 software was used to analyze the data.Results:From 2009 to 2018,the burn patients were 333,995(0.76%),which included 222,480(66.61%)males and 111,515(33.39%)females.From 2009 to 2018,the number of individuals admit-ted to hospitals for burns showed a downward trend year by year.The burn patients accounted for the highest proportion of inpatients in 0-10 years(38.10%),followed by 40-50 years(13.14%).The highest cure ratio of burn inpatients was in the 20-30 age group(31394,71.53%).Among 31 provinces,autonomous regions and municipalities,the province with the highest proportion of total inpatients caused by burns was Inner Mongolia(4.61%),followed by Zhejiang(3.17%),Hainan(2.88%)and Xinjiang(2.64%).Summer(29.16%)was the season with the highest incidence of burn patients admitted to hospitals,followed by spring(25.6%).Scalding(60.19%)was the most frequent kind of burn treated,followed by fire(20.45%).The patients had multiple burn sites(68.89%)most often,followed by burns on the lower limbs(10.91%).From 0%to 10%total body surface area(TBSA)accounted for the highest ratio(37.19%),followed by 90-100%TBSA(21.74%).Conclusions:The present study is the first to describe the associated situation and trends of burn patients in China's Mainland from 2009 to 2018.Our findings will serve as the latest clinical evidence for healthcare planning and prevention efforts in China and other countries.

Correlation between the physical parameters and the electrochemical performance of a silicon anode in lithium-ion batteries

Lithium-ion battery anode used as silicon particles were obtained from different major suppliers,and they were characterized by different spectroscopic techniques and evaluated by electrochemical experiments.Correlations between the key physical parameters and electrochemical properties of the silicon particles were investigated.Silicon particle size,surface oxygen content,-OH content and physical appearance are found to strongly influence the electrochemical properties of the Si anode.The particle size of 100 nm has great promise for the practical application of Si nanoparticles in the lithium-ion battery industry.An inverse correlation between the oxygen content and the reversible capacity or first coulombic efficiency was obtained.The-OH content by surface treatment contributes to enhanced cycling stability by the improved affinity between the Si particle and the water-soluble binder.Spherical Si particles perform better compared to irregular particles,and agglomeration dramatically decreases the cycling stability of the Si anode.Among the investigated Si particles,the sample that exhibited a reversible capacity of more than 2500 mAh g^(-1),a first coulombic efficiency of 89.26%and an excellent cycling stability,has great potential for use in the battery industry.

Umbilical cord-derived mesenchymal stem cells:strategies,challenges,and potential for cutaneous regeneration

Umbilical cord mesenchymal stem cells(MSCs)are a unique,accessible,and non-controversial source of early stem cells that can be readily manipulated.As the most common pluripotent cell,bone marrow-derived MSCs display limitations with the progress of stem cell therapy.By contrast,umbilical cord-derived cells,which have plentiful resources,are more accessible.However,several uncertain aspects,such as the effect of donor selection or culture conditions,long-term therapeutic effects,product consistency,and potential tumorigenicity,are the bottleneck in this clinical therapy.MSCs are predicted to undergo an unprecedented development in clinical treatment when a generally acknowledged criterion emerges.In the current paper,we highlight the application of umbilical cord-derived MSCs in skin therapies based on our previous studies,as well as the achievements of our peers in this field.This paper focuses on the strategies,challenges,and potential of this novel therapy.

3D Bioprinted Skin Substitutes for Accelerated Wound Healing and Reduced Scar

The shortage of skin for grafting continues to be a major problem in the treatment of serious skin injuries.3D bioprinting provides a new way to solve this problem.However,current 3D printed skin is less effective in treatment of large wounds because of severe shrinkage and scarring.In this study,bionically designed bilayer skin was fabricated using an extrusion-based bioprinter and a gelatin/sodium alginate/gelatin methacrylate hydrogel with excellent physical and biological properties.Full-thickness skin wounds were created in the back of nude mice and treated with bioprinted skin or hydrogel.Bioprinted skin accelerated wound healing,reduced wound contraction and scarring,and facilitated wound skin epithelialization compared with the bioprinted hydrogel or untreated wound.The skin from the wound was collected 28 days after grafting for histology and immunofluorescence analysis.The thickness of the dermis and epidermis of the bioprinted skin was similar to that of nude mice.Microvascular formation in the dermis and dense keratinocytes in the epidermis of the bioprinted skin were observed.This study provides a potential treatment strategy for reducing skin contraction and scar in large skin wounds.

Capacity of human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like cells:a preclinical study

Human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)possess various advantageous properties,including self-renewal,extended proliferation potential,multi-lineage differentiation potential and capacity for differentiating into sweat gland-like cells in certain conditions.However,little is known about the effect of clinical-grade culture conditions on these properties and on the differentiative potential of hUC-MSCs.In this study,we sought to investigate the properties of hUC-MSCs expanded with animal serum free culture media(ASFCM)in order to determine their potential for differentiation into sweat gland-like cells.We found that primary cultures of hUC-MSCs could be established with ASFCM.Moreover,cells cultured in ASFCM showed vigorous proliferation comparable to those of cells grown in classical culture conditions containing fetal bovine serum(FBS).Morphology of hUC-MSCs cultured in ASFCM was comparable to those of cells grown under classical culture conditions,and hUC-MSCs grown in both of the two culture conditions tested showed the typical antigen profile of MSCs—positive for CD29,CD44,CD90,and CD105,and negative for CD34 and CD45,as expected.Chromosomal aberration assay revealed that the cells were stable after long-term culture under both culture conditions.Like normal cultured MSCs,hUC-MSCs induced under ASFCM conditions exhibited expression of the same markers(CEA,CK14 and CK19)and developmental genes(EDA and EDAR)that are characteristic of normal sweat gland cells.Taken together,our findings indicate that the classical culture medium used to differentiate hUC-MSCs into sweat gland-like cells can be replaced safely by ASFCM for clinical purposes.

Nerve transfer with 3D-printed branch nerve conduits

Background:Nerve transfer is an important clinical surgical procedure for nerve repair by the coaptation of a healthy donor nerve to an injured nerve.Usually,nerve transfer is performed in an end-to-end manner,which will lead to functional loss of the donor nerve.In this study,we aimed to evaluate the efficacy of 3D-printed branch nerve conduits in nerve transfer.Methods:Customized branch conduits were constructed using gelatine-methacryloyl by 3D print-ing.The nerve conduits were characterized both in vitro and in vivo.The efficacy of 3D-printed branch nerve conduits in nerve transfer was evaluated in rats through electrophysiology testing and histological evaluation.Results:The results obtained showed that a single nerve stump could form a complex nerve network in the 3D-printed multibranch conduit.A two-branch conduit was 3D printed for transferring the tibial nerve to the peroneal nerve in rats.In this process,the two branches were connected to the distal tibial nerve and peroneal nerve.It was found that the two nerves were successfully repaired with functional recovery.Conclusions:It is implied that the two-branch conduit could not only repair the peroneal nerve but also preserve partial function of the donor tibial nerve.This work demonstrated that 3D-printed branch nerve conduits provide a potential method for nerve transfer.