Tetrahedral framework nucleic acids/hyaluronic acidmethacrylic anhydride hybrid hydrogel with antimicrobial and anti-inflammatory properties for infected wound healing

Bacterial resistance and excessive inflammation are common issues that hinder wound healing.Antimicrobial peptides(AMPs)offer a promising and versatile antibacterial option compared to traditional antibiotics,with additional anti-inflammatory properties.However,the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation.TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs.Therefore,in this study,a composite hydrogel(HAMA/t-GL13K)was prepared via the photocross-linking method,in which tFNAs carry GL13K.The hydrogel was injectable,biocompatible,and could be instantly photocured.It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS.Thereby,the hydrogel inhibited bacterial infection,shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring.The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.

A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.

Tetrahedral Framework Nucleic Acid-Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity

Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.

Angiogenesis in a 3D model containing adipose tissue stem cells and endothelial cells is mediated by canonical Wnt signaling

Adipose-derived stromal cells （ASCs） have gained great attention in regenerative medicine. Progress in our understanding of adult neovascularization further suggests the potential of ASCs in promoting vascular regeneration, although the specific cues that stimulate their angiogenic behavior remain controversial In this study, we established a three-dimensional （3D） angiogenesis model by co-culturing ASCs and endothelial cells （ECs） in collagen gel and found that ASC-EC-instructed angiogenesis was regulated by the canonical Wnt pathway. Furthermore, the angiogenesis that occurred in implants collected after injections of our collagen gel- based 3D angiogenesis model into nude mice was confirmed to be functional and also regulated by the canonical Wnt pathway. Wnt regulation of angiogenesis involving changes in vessel length, vessel density, vessel sprout, and connection numbers occurred in our system. Wnt signaling was then shown to regulate ASC- mediated paracrine signaling during angiogenesis through the nuclear translocation of β-catenin after its cytoplasmic accumulation in both ASCs and ECs. This translocation enhanced the expression of nuclear cofactor Lef-1 and cyclin D1 and activated the angiogenic transcription of vascular endothelial growth factor A （VEGFA）, basic fibroblast growth factor （bFGF）, and insulin-like growth factor 1 （IGF-1）. The angiogenesis process in the 3D collagen model appeared to follow canonical Wnt signaling, and this model can help us understand the importance of the canonical Wnt pathway in the use of ASCs in vascular regeneration.

Correction to:Tetrahedral Framework Nucleic Acid‑Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity

Correction to:Nano‑Micro Lett.(2021)13:86 https://doi.org/10.1007/s40820-021-00614-6 The Nano-Micro Letters(2021)13:86,article by Li et al.,entitled“Tetrahedral Framework Nucleic Acid‐Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity”(Nano-Micro Lett.https://doi.org/10.1007/s40820-021-00614-6),was published online 06 March,2020,with errors.

Nanomaterials and bone regeneration

The worldwide incidence of bone disorders and conditions has been increasing. Bone is a nanomaterials composed of organic （mainly collagen） and inorganic （mainly nano-hydroxyapatite） components, with a hierarchical structure ranging from nanoscale to macroscale. In consideration of the serious limitation in traditional therapies, nanomaterials provide some new strategy in bone regeneration. Nanostructured scaffolds provide a closer structural support approximation to native bone architecture for the cells and regulate cell proliferation, differentiation, and migration, which results in the formation of functional tissues. In this article, we focused on reviewing the classification and design of nanostructured materials and nanocarrier materials for bone regeneration, their cell interaction properties, and their application in bone tissue engineering and regeneration. Furthermore, some new challenges about the future research on the application of nanomaterials for bone regeneration are described in the conclusion and perspectives part.

The fabrication of biomimetic biphasic CAN-PAC hydrogel with a seamless interfacial layer applied in osteochondral defect repair

Cartilage tissue engineering based on biomimetic scaffolds has become a rapidly developing strategy for repairing cartilage defects. In this study, a biphasic CAN-PAC hydrogel for osteochondral defect(OCD)regeneration was fabricated based on the density difference between the two layers via a thermally reactive,rapid cross-linking method. The upper hydrogel was cross-linked by CSMA and NIPAm, and the lower hydrogel was composed of PECDA, AAm and PEGDA. The interface between the two layers was first grafted by the physical cross-linking of calcium gluconate and alginate, followed by the chemical cross-linking of the carbon-carbon double bonds in the other components. The pore sizes of the upper and lower hydrogels were ~ 187.4 and ~ 112.6 μm, respectively. The moduli of the upper and lower hydrogels were ~ 0.065 and~ 0.261 MPa. This prepared bilayer hydrogel exhibited the characteristics of mimetic composition, mimetic structure and mimetic stiffness, which provided a microenvironment for sustaining cell attachment and viability. Meanwhile, the biodegradability and biocompatibility of the CAN-PAC hydrogel were examined in vivo. Furthermore, an osteochondral defect model was developed in rabbits, and the bilayer hydrogels were implanted into the defect. The regenerated tissues in the bilayer hydrogel group exhibited new translucent cartilage and repaired subchondral bone, indicating that the hydrogel can enhance the repair of osteochondral defects.

Multi?targeted Antisense Oligonucleotide Delivery by a Framework Nucleic Acid for Inhibiting Biofilm Formation and Virulence

Biofilm formation is responsible for numerous chronic infections and represents a serious health challenge.Bacteria and the extracellular polysaccharides(EPS)cause biofilms to become adherent,toxic,resistant to antibiotics,and ultimately difficult to remove.Inhibition of EPS synthesis can prevent the formation of bacterial biofilms,reduce their robustness,and promote removal.Here,we have developed a framework nucleic acid delivery system with a tetrahedral configuration.It can easily access bacterial cells and functions by delivering antisense oligonucleotides that target specific genes.We designed antisense oligonucleotide sequences with multiple targets based on conserved regions of the VicK protein-binding site.Once delivered to bacterial cells,they significantly decreased EPS synthesis and biofilm thickness.Compared to existing approaches,this system is highly efficacious because it simultaneously reduces the expression of all targeted genes(gtfBCD,gbpB,ftf).We demonstrate a novel nucleic acid-based nanomaterial with multi-targeted inhibition that has great potential for the treatment of chronic infections caused by biofilms.

Osteogenesis of Adipose-Derived Stem Cells

Current treatment options for skeletal repair, including immobilization, rigid fixation, alloplastic materials and bone grafts, have significant limitations. Bone tissue engineering offers a promising method for the repair of bone deficieny caused by fractures, bone loss and tumors. The use of adipose derived stem cells （ASCs） has received attention because of the self-renewal ability, high proliferative capacity and potential of osteogenic differentiation in vitro and in vivo studies of bone regeneration. Although cell therapies using ASCs are widely promising in various clinical fields, no large human clinical trials exist for bone tissue engineering. The aim of this review is to introduce how they are harvested, examine the characterization of ASCs, to review the mechanisms of osteogenic differentiation, to analyze the effect of mechanical and chemical stimuli on ASC osteodifferentiation, to summarize the current knowledge about usage of ASC in vivo studies and clinical trials, and finally to conclude with a general summary of the field and comments on its future direction.

Effects of tetrahedral framework nucleic acid/wogonin complexes on osteoarthritis

Osteoarthritis, a disorder characterized by articular cartilage deterioration, varying degrees of inflammation, and chondrocyte apoptosis, is the most common chronic joint disease. To slow or reverse its progression, inflammation should be inhibited, and chondrocyte proliferation should be promoted. Tetrahedral framework nucleic acids can be internalized by chondrocytes(even inflammatory chondrocytes) and can enhance their proliferation and migration. Wogonin, a naturally occurring flavonoid,suppresses oxidative stress and inhibits inflammation. In this study, tetrahedral framework nucleic acids were successfully selfassembled and used to load wogonin. We confirmed the effective formation of tetrahedral framework nucleic acid/wogonin complexes by dynamic light scattering, zeta potential analysis, transmission electron microscopy, and fluorescence spectrophotometry. Tetrahedral framework nucleic acids, wogonin, and especially tetrahedral framework nucleic acid/wogonin complexes effectively alleviated inflammation in vitro and in vivo and prevented cartilage destruction. In addition, these materials remarkably downregulated the expression of inflammatory mediators and matrix metalloproteinases, upregulated chondrogenic markers, and promoted tissue inhibitor of metalloproteinase 1 and B-cell lymphoma 2 expression. In vivo, after treatment with tetrahedral framework nucleic acid/wogonin complexes, the bone mineral density in regenerated tissues was much higher than that found in the untreated groups. Histologically, the complexes enhanced new tissue regeneration, significantly suppressed chondrocyte apoptosis, and promoted chondrogenic marker expression. They also inhibited cell apoptosis, increased chondrogenic marker expression, and suppressed the expression of inflammatory mediators in osteoarthritis. Therefore, we believe that tetrahedral framework nucleic acid/wogonin complexes can be used as an injectable form of therapy for osteoarthritis.

Comparison of Effects of Mechanical Stretching on Osteogenic Potential of ASCs and BMSCs

Mechanical forces play critical roles in the development and remodeling processes of bone. As an alternative cell source for bone engineering, adipose-derived stem cells （ASCs） should be fully investigated for their responses to mechanical stress. Similarly, the osteogenic potential, stimulated by mechanical stress, should be compared with bone marrow stromal cells （BMSCs）, which have been clinically used for bone tissue engineering. In this study, ASCs and BMSCs were osteogenic-induced for 48 hours, and then subjected to uniaxial mechanical stretching for 2 or 6 hours. Cell orientation, osteogenic regulatory genes, osteogenic genes and ALP activities were measured and compared between ASCs and BMSCs. ASCs could align in a perpendicular way to the direction of stretching stress, while BMSCs did not present a specific alignment. Both 2 and 6 hours mechanical stretching could enhance the mRNA expression of Osx and Runx2 in BMSCs and ASCs, while OCN mRNA only increased in ASCs after 6 hours mechanical loading. Mechanical stretching enhanced the BMP-2 mRNA expression in ASCs, while only after 6 hours of mechanical loading significantly increased the BMP-2 gene expression in BMSCs. Significant differences only exist between ASCs and BMSCs loaded at 2 hours of mechanical stretching. It is concluded that ASCs are more rapid responders to mechanical stress, and have greater potential than BMSCs in osteogenesis when stimulated by mechanical stretching, indicating their usefulness for bone study in a rat model.

Nucleic acids and analogs for bone regeneration

With the incidence of different bone diseases increasing, effective therapies are needed that coordinate a combination of various technologies and biological materials. Bone tissue engineering has also been considered as a promising strategy to repair various bone defects. Therefore, different biological materials that can promote stem cell proliferation, migration, and osteoblastic differentiation to accelerate bone tissue regeneration and repair have also become the focus of research in multiple fields. Stem cell therapy, biomaterial scaffolds, and biological growth factors have shown potential for bone tissue engineering; however, off-target effects and cytotoxicity have limited their clinical use. The application of nucleic acids(deoxyribonucleic acid or ribonucleic acid)and nucleic acid analogs(peptide nucleic acids or locked nucleic acids), which are designed based on foreign genes or with special structures, can be taken up by target cells to exert different effects such as modulating protein expression, replacing a missing gene, or targeting specific gens or proteins. Due to some drawbacks, nucleic acids and nucleic acid analogs are combined with various delivery systems to exert enhanced effects, but current studies of these molecules have not yet satisfied clinical requirements. In-depth studies of nucleic acid or nucleic acid analog delivery systems have been performed, with a particular focus on bone tissue regeneration and repair. In this review, we mainly introduce delivery systems for nucleic acids and nucleic acid analogs and their applications in bone repair and regeneration. At the same time, the application of conventional scaffold materials for the delivery of nucleic acids and nucleic acid analogs is also discussed.

Advances in regenerative medicine applications of tetrahedral framework nucleic acid-based nanomaterials: an expert consensus recommendation

With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising nanostructures are tetrahedral framework nucleic acids(t FNAs), first proposed by Turberfield with the use of a one-step annealing approach. Benefiting from their various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, and editable functionality, t FNAs have been widely applied in the biomedical field as threedimensional DNA nanomaterials. Surprisingly, t FNAs exhibit positive effects on cellular biological behaviors and tissue regeneration,which may be used to treat inflammatory and degenerative diseases. According to their intended application and carrying capacity,t FNAs could carry functional nucleic acids or therapeutic molecules through extended sequences, sticky-end hybridization,intercalation, and encapsulation based on the Watson and Crick principle. Additionally, dynamic t FNAs also have potential applications in controlled and targeted therapies. This review summarized the latest progress in pure/modified/dynamic t FNAs and demonstrated their regenerative medicine applications. These applications include promoting the regeneration of the bone,cartilage, nerve, skin, vasculature, or muscle and treating diseases such as bone defects, neurological disorders, joint-related inflammatory diseases, periodontitis, and immune diseases.

Prospects and challenges of dynamic DNA nanostructures in biomedical applications

The physicochemical nature of DNA allows the assembly of highly predictable structures via several fabrication strategies, which have been applied to make breakthroughs in various fields. Moreover, DNA nanostructures are regarded as materials with excellent editability and biocompatibility for biomedical applications. The ongoing maintenance and release of new DNA structure design tools ease the work and make large and arbitrary DNA structures feasible for different applications. However, the nature of DNA nanostructures endows them with several stimulus-responsive mechanisms capable of responding to biomolecules, such as nucleic acids and proteins, as well as biophysical environmental parameters, such as temperature and p H. Via these mechanisms, stimulus-responsive dynamic DNA nanostructures have been applied in several biomedical settings, including basic research, active drug delivery, biosensor development, and tissue engineering. These applications have shown the versatility of dynamic DNA nanostructures, with unignorable merits that exceed those of their traditional counterparts, such as polymers and metal particles.However, there are stability, yield, exogenous DNA, and ethical considerations regarding their clinical translation. In this review, we first introduce the recent efforts and discoveries in DNA nanotechnology, highlighting the uses of dynamic DNA nanostructures in biomedical applications. Then, several dynamic DNA nanostructures are presented, and their typical biomedical applications,including their use as DNA aptamers, ion concentration/p H-sensitive DNA molecules, DNA nanostructures capable of strand displacement reactions, and protein-based dynamic DNA nanostructures, are discussed. Finally, the challenges regarding the biomedical applications of dynamic DNA nanostructures are discussed.

Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis

The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw(BRONJ)is the exposure of the necrotic jaw.Other clinical manifestations include jaw pain,swelling,abscess,and skin fistula,which seriously affect the patients’life,and there is no radical cure.Thus,new methods need to be found to prevent the occurrence of BRONJ.Here,a novel nanoparticle,t FNA-KLT,was successfully synthesized by us,in which the nanoparticle tetrahedral framework nucleic acid(tFNA)was used for carrying angiogenic peptide,KLT,and then further enhanced angiogenesis.TFNA-KLT possessed the same characteristics as tFNA,such as simple synthesis,stable structure,and good biocompatibility.Meanwhile,tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells.First,it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo.Then we apply tFNA-KLT to the prevention of BRONJ.The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis.In summary,the prepared novel nanoparticle,tFNA-KLT,was firstly synthesized by us.It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis,thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis.

Crosstalk between adipose-derived stem cells and chondrocytes:when growth factors matter

Adipose-derived stem cells（ASCs）and mesenchymal stem cells are promising for tissue repair because of their multilineage differentiation capacity.Our previous data confirmed that the implantation of mixed ASCs and chondrocytes into cartilage defects induced desirable in vivo healing outcomes.However,the paracrine action of ASCs on chondrocytes needs to be further elucidated.In this study,we established a co-culture system to achieve cell-to-cell and cell-to-tissue crosstalk and explored the soluble growth factors in both ASCs and chondrocytes supplemented with 1%fetal bovine serum to mimic the physiological microenvironment.In ASCs,we screened for growth factors by semi-quantitative PCR and quantitative real-time PCR and found that the expression of bone morphogenetic protein 2（BMP-2）,vascular endothelial growth factor B（VEGFB）,hypoxia inducible factor-1α（HIF-1α）,fibroblast growth factor-2（FGF-2）,and transforming growth factor-β1 significantly increased after co-culture in comparison with mono-culture.In chondrocytes,VEGFA was significantly enhanced after co-culture.Unexpectedly,the expression of collagen II and aggrecan was significantly down-regulated in the co-culture group compared with the mono-culture group.Meanwhile,among all the growth factors screened,we found that the BMP family members BMP-2,BMP-4,and BMP-5 were down-regulated and that VEGFB,HIF-1α,FGF-2,and PDGF were significantly decreased after co-culture.These results suggest that crosstalk between ASCs and chondrocytes is a pathway through the regulated growth factors that might have potential in cartilage repair and regeneration and could be useful for tissue engineering.

DNA framework signal amplification platform-based highthroughput systemic immune monitoring

Systemic immune monitoring is a crucial clinical tool for disease early diagnosis,prognosis and treatment planning by quantitative analysis of immune cells.However,conventional immune monitoring using flow cytometry faces huge challenges in large-scale sample testing,especially in mass health screenings,because of time-consuming,technical-sensitive and high-cost features.However,the lack of high-performance detection platforms hinders the development of high-throughput immune monitoring technology.To address this bottleneck,we constructed a generally applicable DNA framework signal amplification platform(DSAP)based on post-systematic evolution of ligands by exponential enrichment and DNA tetrahedral framework-structured probe design to achieve high-sensitive detection for diverse immune cells,including CD4+,CD8+T-lymphocytes,and monocytes(down to 1/100μl).Based on this advanced detection platform,we present a novel high-throughput immune-cell phenotyping system,DSAP,achieving 30-min one-step immune-cell phenotyping without cell washing and subset analysis and showing comparable accuracy with flow cytometry while significantly reducing detection time and cost.As a proof-of-concept,DSAP demonstrates excellent diagnostic accuracy in immunodeficiency staging for 107 HIV patients(AUC>0.97)within 30 min,which can be applied in HIV infection monitoring and screening.Therefore,we initially introduced promising DSAP to achieve high-throughput immune monitoring and open robust routes for point-of-care device development.

Transdermal treatment for malignant melanoma by aptamer-modified tetrahedral framework nucleic acid delivery of vemurafenib

Melanoma is one of the most malignant skin tumors, whose high invasion is generally associated with BRAF gene mutation. Although new chemotherapeutic drugs, such as vemurafenib, have been developed to inhibit the growth of melanoma, these drugs are usually administered intravenously or orally, resulting in toxic side effects on major tissues and organs. Tetrahedral framework nucleic acids(tFNAs) are a novel type of DNA nanostructures with excellent biocompatibility and versatility which have been proven to penetrate through skin barrier with ease. In this study, we prepared t FNAs with vemurafenib and connected DNA aptamer AS1411 at the apex of t FNAs(AS1411-tFNAs/vemurafenib). On one hand, AS1411-tFNAs/vemurafenib could kill melanoma cells by blocking the mutated BRAF gene in vitro. Compared with free vemurafenib, AS1411-tFNAs/vemurafenib had no obvious toxicity to normal cells. On the other hand,AS1411-tFNAs could transfer vemurafenib to cross through the skin barrier and permeate into tumor tissues. In vivo, transdermal delivery of AS1411-t FNAs/vemurafenib could inhibit the growth of human A375melanoma, whose inhibiting effect was stronger than intravenous administration of vemurafenib. These results demonstrated the application prospects of tFNAs combined with chemotherapeutic drugs in skin tumors.

Tetrahedral framework nucleic acids promote the proliferation and differentiation potential of diabetic bone marrow mesenchymal stem cell

Diabetes mellitus considerably affects bone marrow mesenchymal stem cells(BMSCs),for example,by inhibiting their proliferation and differentiation potential,which enhances the difficulty in endogenous bone regeneration.Hence,effective strategies for enhancing the functions of BMSCs in diabetes have farreaching consequences for bone healing and regeneration in diabetes patients.Tetrahedral framework nucleic acids(tFNAs)are nucleic acid nanomaterials that can autonomously enter cells and regulate their behaviors.In this study,we evaluated the effects of tFNAs on BMSCs from diabetic rats.We found that tFNAs could promote the proliferation,migration,and osteogenic differentiation of BMSCs from rats with type 2 diabetes mellitus,and inhibited cell senescence and apoptosis.Furthermore,tFNAs effectively scavenged the accumulated reactive oxygen species and activated the suppressed protein kinase B(Akt)signaling pathway.Overall,we show that tFNAs can recover the proliferation and osteogenic potential of diabetic BMSCs by alleviating oxidative stress and activating Akt signaling.The study provides a strategy for endogenous bone regeneration in diabetes and also paves the way for exploiting DNA-based nanomaterials in regenerative medicine.

Tetrahedral framework nucleic acids promote scarless healing of cutaneous wounds via the AKT-signaling pathway

While the skin is considered the first line of defense in the human body,there are some vulnerabilities that render it susceptible to certain threats,which is an issue that is recognized by both patients and doctors.Cutaneous wound healing is a series of complex processes that involve many types of cells,such as fibroblasts and keratinocytes.This study showed that tetrahedral framework nucleic acids(tFNAs),a type of self-assembled nucleic-acid material,have the ability to promote keratinocyte(HaCaT cell line)and fibroblast(HSF cell line)proliferation and migration in vitro.In addition,tFNAs increased the secretion of vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)in HSF cells and reduced the production of tumor necrosis factor-alpha(TNF-α)and interleukin-1 beta(IL-1β)in HaCaT cells by activating the AKT-signaling pathway.During in vivo experiments,tFNA treatments accelerated the healing process in skin wounds and decreased the development of scars,compared with the control treatment that did not use tFNAs.This is the first study to demonstrate that nanophase materials with the biological features of nucleic acids accelerate the healing of cutaneous wounds and reduce scarring,which indicates the potential application of tFNAs in skin tissue regeneration.