Association analysis of BclI with benign lymphoepithelial lesions of the lacrimal gland and glucocorticoids resistance

AIM:To evaluate the relationship between gene polymorphism(BclI,ER22/23EK,N363S)and the occurrence,progression and sensitivity to glucocorticoid of lacrimal gland benign lymphoepithelial lesion(LGBLEL).METHODS:Clinical peripheral blood samples of 52 LGBLEL patients and 10 normal volunteers were collected for DNA extraction and polymerase chain reaction sequencing to analyze single nucleotide polymorphism(SNP)genotypes.The lacrimal tissues of LGBLEL were surgically removed and made into paraffin sections for subsequent hematoxylin-eosin(HE)and Masson staining analysis.The duration of disease and hormone use of LGBLEL patients from diagnosis to surgery were also analyzed.The Meta-analysis follows PRISMA guidelines to conducted a systematic review of human studies investigating the relationship between the NR3C1 BclI polymorphism and glucocorticoids(GCs)sensitivity.RESULTS:There was no association between ER22/23EK or N363S and the occurrence of LGBLEL or GCs sensitivity(P>0.05);BclI GC genotype was closely related to GCs resistance(P=0.03)as is the minor allele C(P=0.0017).The HE staining and Masson staining showed that the GC genotype of BclI remarkably slowed down the disease progression and reduced fibrosis(P<0.05),especially for GCs-dependent patients(P<0.0001).Meta-analysis showed that BclI was not significantly associated with GCs responsiveness.CONCLUSION:The LGBLEL patients who carry the NR3C1 BclI allele C may be more sensitive to GCs and associated with lower fibrosis and slower disease progression.The results may guide the clinical treatment strategy for the LGBLEL patients.

Advancing antimicrobial strategies for managing oral biofilm infections

Effective control of oral biofilm infectious diseases represents a major global challenge.Microorganisms in biofilms exhibit increased drug tolerance compared with planktonic cells.The present review covers innovative antimicrobial strategies for controlling oral biofilm-related infections published predominantly over the past 5 years.Antimicrobial dental materials based on antimicrobial agent release,contact-killing and multi-functional strategies have been designed and synthesized for the prevention of initial bacterial attachment and subsequent biofilm formation on the tooth and material surface.Among the therapeutic approaches for managing biofilms in clinical practice,antimicrobial photodynamic therapy has emerged as an alternative to antimicrobial regimes and mechanical removal of biofilms,and cold atmospheric plasma shows significant advantages over conventional antimicrobial approaches.Nevertheless,more preclinical studies and appropriately designed and well-structured multi-center clinical trials are critically needed to obtain reliable comparative data.The acquired information will be helpful in identifying the most effective antibacterial solutions and the most optimal circumstances to utilize these strategies.

Relationship of distraction rate with inferior alveolar nerve degeneration-regeneration shift

Distraction osteogenesis is an important technique for the treatment of maxillofacial abnormities and defects. However, distraction osteo- genesis may cause the injury of the inferior alveolar nerve. The relationship between distraction rate and nerve degeneration-regeneration shift remains poorly understood. In this study, 24 rabbits were randomly divided into four groups. To establish the rabbit mandibular distraction osteogenesis model, the mandibles of rabbits in distraction osteogenesis groups were subjected to continuous osteogenesis dis- traction at a rate of 1.0, 1.5 and 2.0 mm/d, respectively, by controlling rounds of screwing each day in the distractors. In the sham group, mandible osteotomy was performed without distraction, Pin-prick test with a 10 g blunt pin on the labium, histological and histomorpho- metric analyses with methylene blue staining, Bodian＇s silver staining, transmission electron microscopy and myelinated fiber density of inferior alveolar nerve cross-sections were performed to assess inferior alveolar nerve conditions. At 28 days after model establishment, in the pin-prick test, the inferior alveolar nerve showed no response in the labium to a pin pricks in the 2 mm/d group, indicating a severe dysfunction. Histological and histomorphometric analyses indicated that the inferior alveolar nerve suffered more degeneration and in- juries at a high distraction rate （2 mm/d）. Importantly, the nerve regeneration, indicated by newborn Schwann cells and axons, was more abundant in 1.0 and 1.5 mm/d groups than in 2.0 mm/d group. We concluded that the distraction rate was strongly associated with the inferior alveolar nerve function, and the distraction rates of !.0 and 1.5 mm/d had regenerative effects on the inferior alveolar nerve. This study provides an experimental basis for the relationship between distraction rate and nerve degeneration-regeneration shift during dis- traction osteogenesis, and may facilitate reducing nerve complications during distraction osteogenesis.

Rescuing“hopeless”avulsed teeth using autologous platelet-rich fibrin following delayed reimplantation:Two case reports

BACKGROUND Tooth avulsion is one of the most severe types of dental trauma.Most avulsed teeth undergo long-term ankylosis and replacement resorption after delayed reimplantation and exhibit a poor prognosis.The aim of this work was to improve the success rate of avulsed teeth after delayed reimplantation using autologous platelet-rich fibrin(PRF).CASE SUMMARY Case 1 was a 14-year-old boy who fell and knocked out his left upper central incisor 18 h prior to his arrival at the department.The diagnoses were avulsion of tooth 21,lateral luxation of tooth 11 and alveolar fracture of teeth 11 and 21.In case 2,a 17-year-old boy fell 2 h prior to his presentation to the hospital,and his left upper lateral incisor was completely knocked out of the alveolar socket.The diagnoses included avulsion of tooth 22,complicated crown fracture of tooth 11and complicated crown-root fracture of tooth 21.The avulsed teeth were reimplanted along with autologous PRF granules and splinted using a semiflexible titanium preshaped labial arch.The root canals of the avulsed teeth were filled with calcium hydroxide paste,and root canal filling was performed 4 wk after reimplantation.The reimplanted teeth showed no symptoms of inflammatory root resorption or ankylosis at the 3-,6-,and 12-mo follow-up examinations after reimplantation with autologous PRF.In addition to the avulsed teeth,the other injured teeth were treated using corresponding conventional treatment methods.CONCLUSION These cases provide examples of the successful use of PRF to reduce pathological root resorption of the avulsed teeth,and the application of PRF may provide new healing opportunities for traditionally“hopeless”avulsed teeth.

MSCs-derived apoptotic extracellular vesicles promote muscle regeneration by inducing Pannexin 1 channel-dependent creatine release by myoblasts

Severe muscle injury is hard to heal and always results in a poor prognosis.Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine,however,whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown.Herein,we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells(MSCs-Apo EVs)to treat cardiotoxin induced tibialis anterior(TA)injury and found that MSCs-Apo EVs promoted muscles regeneration and increased the proportion of multinucleated cells.Besides that,we also found that apoptosis was synchronized during myoblasts fusion and MSCs-Apo EVs promoted the apoptosis ratio as well as the fusion index of myoblasts.Furthermore,we revealed that MSCs-Apo EVs increased the relative level of creatine during myoblasts fusion,which was released via activated Pannexin 1 channel.Moreover,we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived Apo EVs(Myo-Apo EVs)instead of apoptotic myoblasts,and creatine was the pivotal metabolite involved in myoblasts fusion.Collectively,our findings firstly revealed that MSCs-Apo EVs can promote muscle regeneration and elucidated that the new function of Apo EVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel,which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.

LncRNA GACAT2 binds with protein PKM1/2 to regulate cell mitochondrial function and cementogenesis in an inflammatory environment

Periodontal ligament stem cells(PDLSCs) are a key cell type for restoring/regenerating lost/damaged periodontal tissues, including alveolar bone, periodontal ligament and root cementum, the latter of which is important for regaining tooth function. However,PDLSCs residing in an inflammatory environment generally exhibit compromised functions, as demonstrated by an impaired ability to differentiate into cementoblasts, which are responsible for regrowing the cementum. This study investigated the role of mitochondrial function and downstream long noncoding RNAs(lnc RNAs) in regulating inflammation-induced changes in the cementogenesis of PDLSCs. We found that the inflammatory cytokine-induced impairment of the cementogenesis of PDLSCs was closely correlated with their mitochondrial function, and lnc RNA microarray analysis and gain/loss-of-function studies identified GACAT2 as a regulator of the cellular events involved in inflammation-mediated mitochondrial function and cementogenesis.Subsequently, a comprehensive identification of RNA-binding proteins by mass spectrometry(Ch IRP-MS) and parallel reaction monitoring(PRM) assays revealed that GACAT2 could directly bind to pyruvate kinase M1/2(PKM1/2), a protein correlated with mitochondrial function. Further functional studies demonstrated that GACAT2 overexpression increased the cellular protein expression of PKM1/2, the PKM2 tetramer and phosphorylated PKM2, which led to enhanced pyruvate kinase(PK) activity and increased translocation of PKM2 into mitochondria. We then found that GACAT2 overexpression could reverse the damage to mitochondrial function and cementoblastic differentiation of PDLSCs induced by inflammation and that this effect could be abolished by PKM1/2 knockdown. Our data indicated that by binding to PKM1/2 proteins, the lnc RNA GACAT2 plays a critical role in regulating mitochondrial function and cementogenesis in an inflammatory environment.

Ionomycin ameliorates hypophosphatasia via rescuing alkaline phosphatase deficiency-mediated L-type Ca^(2+) channel internalization in mesenchymal stem cells

The loss-of-function mutations in the ALPL result in hypophosphatasia(HPP), an inborn metabolic disorder that causes skeletal mineralization defects. In adults, the main clinical features are early loss of primary or secondary teeth, osteoporosis, bone pain,chondrocalcinosis, and fractures. However, guidelines for the treatment of adults with HPP are not available. Here, we show that ALPL deficiency caused a reduction in intracellular Ca2+ influx, resulting in an osteoporotic phenotype due to downregulated osteogenic differentiation and upregulated adipogenic differentiation in both human and mouse bone marrow mesenchymal stem cells(BMSCs). Increasing the intracellular level of calcium in BMSCs by ionomycin treatment rescued the osteoporotic phenotype in alpl+/- mice and BMSC-specific(Prrx1-alpl-/-) conditional alpl knockout mice. Mechanistically, ALPL was found to be required for the maintenance of intracellular Ca2+ influx, which it achieves by regulating L-type Ca2+ channel trafficking via binding to the α2δsubunits to regulate the internalization of the L-type Ca2+ channel. Decreased Ca2+ flux inactivates the Akt/GSK3β/β-catenin signaling pathway, which regulates lineage differentiation of BMSCs. This study identifies a previously unknown role of the ectoenzyme ALPL in the maintenance of calcium channel trafficking to regulate stem cell lineage differentiation and bone homeostasis. Accelerating Ca2+ flux through L-type Ca2+ channels by ionomycin treatment may be a promising therapeutic approach for adult patients with HPP.

Periodontitis may induce gut microbiota dysbiosis via salivary microbiota

The aim of this study was to identify whether periodontitis induces gut microbiota dysbiosis via invasion by salivary microbes.First,faecal and salivary samples were collected from periodontally healthy participants(PH group,n=16)and patients with severe periodontitis(SP group,n=21)and analysed by 16S ribosomal RNA sequencing.Significant differences were observed in both the faecal and salivary microbiota between the PH and SP groups.Notably,more saliva-sourced microbes were observed in the faecal samples of the SP group.Then,the remaining salivary microbes were transplanted into C57BL6/J mice(the C-PH group and the C-SP group),and it was found that the composition of the gut microbiota of the C-SP group was significantly different from that of the C-PH group,with Porphyromonadaceae and Fusobacterium being significantly enriched in the C-SP group.In the colon,the C-SP group showed significantly reduced crypt depth and zonula occludens-1 expression.The m RNA expression levels of pro-inflammatory cytokines,chemokines and tight junction proteins were significantly higher in the C-SP group.To further investigate whether salivary bacteria could persist in the intestine,the salivary microbiota was stained with carboxyfluorescein diacetate succinimidyl ester and transplanted into mice.We found that salivary microbes from both the PH group and the SP group could persist in the gut for at least 24 h.Thus,our data demonstrate that periodontitis may induce gut microbiota dysbiosis through the influx of salivary microbes.

Unique regulation of TiO_(2)nanoporous topography on macrophage polarization via MSC-derived exosomes

The comprehensive recognition of communications between bone marrow mesenchymal stem cells(bm-MSCs)and macrophages in the peri-implant microenvironment is crucial for implantation prognosis.Our previous studies have clarified the indirect influence of Ti surface topography in the osteogenic differentiation of bm-MSCs through modulating macrophage polarization.However,cell communication is commutative and multi-directional.As the immune regulatory properties of MSCs have become increasingly prominent,whether bm-MSCs could also play an immunomodulatory role on macrophages under the influence of Ti surface topography is unclear.To further illuminate the communications between bm-MSCs and macrophages,the bm-MSCs inoculated on Ti with nanoporous topography were indirectly co-cultured with macrophages,and by blocking exosome secretion or extracting the purified exosomes to induce independently,we bidirectionally confirmed that under the influence of TiO_(2)nanoporous topography with 80-100 nm tube diameters,bm-MSCs can exert immunomodulatory effects through exosome-mediated paracrine actions and induce M1 polarization of macrophages,adversely affecting the osteogenic microenvironment around the implant.This finding provides a reference for the optimal design of the implant surface topography for inducing better bone regeneration.

Immunomodulation and osteointegration of infected implants by ion-riched and hierarchical porous TiO_(2)matrix

Infection is a main cause of implant failure.The microenvironment cell experiencing after antimicrobial therapy of infected implants is very crucial for immunomodulation and subsequent osteointegration.Based on the superiority of photothermal therapy in anti-infection,a matrix of nanograined TiO_(2)with(Si/P)-dual ions and hierarchical nano/microporous topography is developed on Ti implant by micro-arc oxidation.It shows good photothermal properties due to the lattice distortion induced by ion doping and can kill bacteria with near-infrared(NIR)light irradiation efficiently.Due to the combined action of porous topography and release of Si/P ions,the TiO_(2)matrix achieves M1-to-M_(2)phenotype switch of macrophages timely at different simulating infection stage and accelerates recruitment,proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.In vivo,the TiO_(2)matrix also shows desired antibacterial performance after photothermal therapy and exhibits outstanding immunomodulatory ability and new bone formation efficiency.This study provides a promising TiO_(2)matrix applied in clinic for settling implant infection by NIR light irradiation and promoting bone regeneration through osteoimmunomodulation.

Self-adaptive hydrogel for breast cancer therapy via accurate tumor elimination and on-demand adipose tissue regeneration

The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer treatment.Herein,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination,on-demand adipose tissue regeneration and effective infection inhibition.The hydrogel consisted of thiol groups ended polyethylene glycol(SH-PEG-SH)and doxorubicin encapsulated mesoporous silica nanocarriers(DOX@MSNs)double crosslinked hyaluronic acid(HA)after loading of antibacterial peptides(AP)and adipose-derived stem cells(ADSCs).A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release,meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs,which contributed to the selective chemotherapy in tumor cells with over-expressed esterase.The bond cleavage between MSNs and HA would also cause the swelling of the hydrogel,which not only provide sufficient space for the growth of ADSCs,but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy,resulting in the on-demand regeneration of adipose tissue.Moreover,the sustained release of AP could be simultaneously triggered along with the size change of hydrogel,which further avoided bacterial infection to promote tissue regeneration.

Advancing application of mesenchymal stem cell-based bone tissue regeneration

Reconstruction of bone defects,especially the critical-sized defects,with mechanical integrity to the skeleton is important for a patient's rehabilitation,however,it still remains challenge.Utilizing biomaterials of human origin bone tissue for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural bone tissue with regard to its properties.However,not only efficacious and safe but also costeffective and convenient are important for regenerative biomaterials to achieve clinical translation and commercial success.Advances in our understanding of regenerative biomaterials and their roles in new bone formation potentially opened a new frontier in the fast-growing field of regenerative medicine.Taking inspiration from the role and multicomponent construction of native extracellular matrix(ECM)for cell accommodation,the ECM-mimicking biomaterials and the naturally decellularized ECM scaffolds were used to create new tissues for bone restoration.On the other hand,with the going deep in understanding of mesenchymal stem cells(MSCs),they have shown great promise to jumpstart and facilitate bone healing even in diseased microenvironments with pharmacology-based endogenous MSCs rescue/mobilization,systemic/local infusion of MSCs for cytotherapy,biomaterials-based approaches,cell-sheets/-aggregates technology and usage of subcellular vesicles of MSCs to achieve scaffolds-free or cell-free delivery system,all of them have been shown can improve MSCsmediated regeneration in preclinical studies and several clinical trials.Here,following an overview discussed autogenous/allogenic and ECM-based bone biomaterials for reconstructive surgery and applications of MSCsmediated bone healing and tissue engineering to further offer principles and effective strategies to optimize MSCs-based bone regeneration.

Laminin 332-functionalized coating to regulate the behavior of keratinocytes and gingival mesenchymal stem cells to enhance implant soft tissue sealing

Peri-implant epithelial sealing is the first line of defense against external pathogens or stimuli;hence,an essential process to prevent peri-implantitis.Laminin 332(LN332)is the main component of the internal basal lamina and participates in peri-implant epithelial sealing by forming hemidesmosomes(HDs)with integrinα6β4.In thiswork,poly(D,L-lactide)(PDLLA)-LN332 composite coating was successfully constructed by a method similar to layer-by-layer assembly,displaying staged LN332 release for as long as 28days.The PDLLA-LN332 composite coating can activate the intracellular PI3K-Akt pathway via binding to cellular integrinα6β4,which can promote adhesion,migration and proliferation of HaCaT cells and further enhance the expression of keratinocyte HD-related molecules,including integrinα6β4,LN332 and plectin.Furthermore,the PDLLA-LN332 composite coating can promote the adhesion,spreading and proliferation of gingival mesenchymal stem cells and accelerate their epithelial differentiation.Therefore,the PDLLA-LN332 composite coating can enhance implant soft tissue sealing,warranting further in vivo study.

Pharmacological manipulation of macrophage autophagy effectively rejuvenates the regenerative potential of biodegrading vascular graft in aging body

Declined regenerative potential and aggravated inflammation upon aging create an inappropriate environment for arterial regeneration.Macrophages are one of vital effector cells in the immune microenvironment,especially during biomaterials mediated repairing process.Here,we revealed that the macrophage autophagy decreased with aging,which led to aggravated inflammation,thereby causing poor vascular remodeling of artificial grafts in aging body.Through loading the autophagy-targeted drugs,rapamycin and 3-MA(3-methyladenine),in PCL(polycaprolactone)sheath of the PGS(poly glycerol sebacate)-PCL vascular graft,the essential role of macrophage autophagy was confirmed in regulating macrophage polarization and biomaterial degradation.Moreover,the utilization of rapamycin promoted anti-inflammatory polarization of macrophage by activating autophagy,which further promoted myogenic differentiation of vascular progenitor cells and accelerated endothelialization.Our study elucidated the contribution of pharmacological manipulation of macrophage autophagy in promoting regeneration of small caliber artery,which may pave a new avenue for clinical translation of vascular grafts in aging body.

Recent developments of droplets-based microfluidics for bacterial analysis

Droplet-based microfluidics enables the generation of uniform microdroplets at picoliter or nanoliter scale with high frequency(∼kHz)under precise control.The droplets can function as bioreactors for versatile chemical/biological study and analysis.Taking advantage of the discrete compartment with a confined volume,(1)isolation and manipulation of a single cell,(2)improvement of in-droplet effective concen-trations,(3)elimination of heterogeneous population effects,(4)diminution of contamination risks can be achieved,making it a powerful tool for rapid,sensitive,and high-throughput detection and analysis of bacteria,even for rare or unculturable strains in conventional methods.This mini-review will focus on the generation and manipulation of micro-droplets and bacteria detection and analysis carried out by droplet-based microfluidics.Finally,applications with high potential of droplet-based bacteria analysis are briefly introduced.Due to the advantages of rapid,sensitive,high throughput,and compatibility with rare and unculturable bacteria in conventional methods,droplet-based microfluidics has tremendous potential of providing novel solutions for biological medicine,microbiological engineering,environmental ecology,etc.

A viscoelastic alginate-based hydrogel network coordinated with spermidine for periodontal ligament regeneration

Periodontitis can cause irreversible defects in the periodontal ligament(PDL),the regeneration of which is the major obstacle to the clinical treatment of periodontitis.Implanting hydrogel for releasing anti-inflammatory drugs is a promising treatment to promote PDL regeneration.However,existing hydrogel systems fail to mimic the typical viscoelastic feature of native periodontium,which may have been shown as an important role in tissue regeneration.Meanwhile,the synergistic benefits of mechanical cues and biochemical agents for PDL regeneration remain elusive.In this study,we developed a bi-crosslinking viscoelastic hydrogel(Alg-PBA/Spd)by integrating phenylboronic acid-modified alginate with anti-inflammatory agent(spermidine)through borate ester and B-N coordination bonds,where spermidine will be released with the degradation of the hydrogel.Alg-PBA/Spd hydrogel is biocompatible,injectable and can quickly adapt to complex periodontal structures due to the dynamic crosslinking.We demonstrated in rat models that the viscoelastic Alg-PBA/Spd hydrogel significantly promotes the deposition of periodontal collagen and accelerates the repair of periodontal damage.Our results suggest that the viscoelastic Alg-PBA/Spd hydrogel would be a promising mechano-biochemically synergistic treatment for periodontal regeneration.

Silicified collagen scaffold induces semaphorin 3A secretion by sensory nerves to improve in-situ bone regeneration

Sensory nerves promote osteogenesis through the release of neuropeptides.However,the potential application and mechanism in which sensory nerves promote healing of bone defects in the presence of biomaterials remain elusive.The present study identified that new bone formation was more abundantly produced after implantation of silicified collagen scaffolds into defects created in the distal femur of rats.The wound sites were accompanied by extensive nerve innervation and angiogenesis.Sensory nerve dysfunction by capsaicin injection resulted in significant inhibition of silicon-induced osteogenesis in the aforementioned rodent model.Application of extracellular silicon in vitro induced axon outgrowth and increased expression of semaphorin 3 A(Sema3A)and semaphorin 4D(Sema4D)in the dorsal root ganglion(DRG),as detected by the upregulation of signaling molecules.Culture medium derived from silicon-stimulated DRG cells promoted proliferation and differentiation of bone marrow mesenchymal stem cells and endothelial progenitor cells.These effects were inhibited by the use of Sema3A neutralizing antibodies but not by Sema4D neutralizing antibodies.Knockdown of Sema3A in DRG blocked silicon-induced osteogenesis and angiogenesis almost completely in a femoral defect rat model,whereas overexpression of Sema3A promoted the silicon-induced phenomena.Activation of“mechanistic target of rapamycin”(mTOR)pathway and increase of Sema3A production were identified in the DRG of rats that were implanted with silicified collagen scaffolds.These findings support the role of silicon in inducing Sema3A production by sensory nerves,which,in turn,stimulates osteogenesis and angiogenesis.Taken together,silicon has therapeutic potential in orthopedic rehabilitation.

Engineered neutrophil apoptotic bodies ameliorate myocardial infarction by promoting macrophage efferocytosis and inflammation resolution

Inflammatory response plays a critical role in myocardial infarction(MI)repair.The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration,while the therapeutic strategy that simulates and enhances this natural process has not been established.Here,we constructed engineered neutrophil apoptotic bodies(eNABs)to simulate natural neutrophil apoptosis,which regulated inflammation response and enhanced MI repair.The eNABs were fabricated by combining natural neutrophil apoptotic body membrane which has excellent inflammation-tropism and immunoregulatory properties,and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride(HAL).The eNABs actively targeted to macrophages and the encapsulated HAL simultaneously initiated the biosynthesis pathway of heme to produce anti-inflammatory bilirubin after intracellular release,thereby further enhancing the anti-inflammation effects.In in vivo studies,the eNABs efficiently modulated inflammation responses in the infarcted region to ameliorate cardiac function.This study demonstrates an effective biomimetic construction strategy to regulate macrophage functions for MI repair.

Biomaterials from the sea:Future building blocks for biomedical applications

Marine resources have tremendous potential for developing high-value biomaterials.The last decade has seen an increasing number of biomaterials that originate from marine organisms.This field is rapidly evolving.Marine biomaterials experience several periods of discovery and development ranging from coralline bone graft to polysaccharide-based biomaterials.The latter are represented by chitin and chitosan,marine-derived collagen,and composites of different organisms of marine origin.The diversity of marine natural products,their properties and applications are discussed thoroughly in the present review.These materials are easily available and possess excellent biocompatibility,biodegradability and potent bioactive characteristics.Important applications of marine biomaterials include medical applications,antimicrobial agents,drug delivery agents,anticoagulants,rehabilitation of diseases such as cardiovascular diseases,bone diseases and diabetes,as well as comestible,cosmetic and industrial applications.

Nanoporous titanium implant surface promotes osteogenesis by suppressing osteoclastogenesis via integrin β1/FAKpY397/MAPK pathway

Macrophages and osteoclasts are both derived from monocyte/macrophage lineage,which plays as the osteoclastic part of bone metabolism.Although they are regulated by bone implant surface nanoarchitecture and involved in osseointegration,the beneath mechanism has not been simultaneously analyzed in a given surface model and their communication with osteoblasts is also blurring.Here,the effect of implant surface topography on monocyte/macrophage lineage osteoclastogenesis and the subsequent effect on osteogenesis are systematically investigated.The nanoporous surface is fabricated on titanium implant by etching and anodizing to get the nanotubes structure.The early bone formation around implant is significantly accelerated by the nanoporous surface in vivo.Meanwhile,the macrophage recruitment and osteoclast formation are increased and decreased respectively.Mechanistically,the integrin mediated FAK phosphorylation and its downstream MAPK pathway(p-p38)are significantly downregulated by the nanoporous surface,which account for the inhibition of osteoclastogenesis.In addition,the nanoporous surface can alleviate the inhibition of osteoclasts on osteogenesis by changing the secretion of clastokines,and accelerate bone regeneration by macrophage cytokine profiles.In conclusion,these data indicate that physical topography of implant surface is a critical factor modulating monocyte/macrophage lineage commitment,which provides theoretical guidance and mechanism basis for promoting osseointegration by coupling the osteogenesis and osteoclastogenesis.