Impact of tibial transverse transport in tissue regeneration and wound healing with perspective on diabetic foot ulcers

In this editorial,we comment on an article by Liao et al published in the current issue of the World Journal of Diabetes.We focus on the clinical significance of tibial transverse transport(TTT)as an effective treatment for patients with diabetic foot ulcers(DFU).TTT has been associated with tissue regeneration,improved blood circulation,reduced amputation rates,and increased expression of early angiogenic factors.Mechanistically,TTT can influence macrophage polarization and growth factor upregulation.Despite this potential,the limitations and conflicting results of existing studies justify the need for further research into its optimal application and development.These clinical implications highlight the efficacy of TTT in recalcitrant DFU and provide lasting stimuli for tissue re-generation,and blood vessel and bone marrow improvement.Immunomodu-lation via systemic responses contributes to its therapeutic potential.Future studies should investigate the underlying molecular mechanisms to enhance our understanding and the efficacy of TTT.This manuscript emphasizes the potential of TTT in limb preservation and diabetic wound healing and suggests avenues for preventive measures against limb amputation in diabetes and peripheral artery disease.Here,we highlight the clinical significance of the TTT and its importance in healing DFU to promote the use of this technique in tissue regeneration.

Embedding aligned nanofibrous architectures within 3D-printed polycaprolactone scaffolds for directed cellular infiltration and tissue regeneration

Three-dimensional(3D) printing provides a promising way to fabricate biodegradable scaffolds with designer architectures for the regeneration of various tissues.However,the existing3D-printed scaffolds commonly suffer from weak cell-scaffold interactions and insufficient cell organizations due to the limited resolution of the 3D-printed features.Here,composite scaffolds with mechanically-robust frameworks and aligned nanofibrous architectures are presented and hybrid manufactured by combining techniques of 3D printing,electrospinning,and unidirectional freeze-casting.It was found that the composite scaffolds provided volume-stable environments and enabled directed cellular infiltration for tissue regeneration.In particular,the nanofibrous architectures with aligned micropores served as artificial extracellular matrix materials and improved the attachment,proliferation,and infiltration of cells.The proposed scaffolds can also support the adipogenic maturation of adipose-derived stem cells(ADSCs)in vitro.Moreover,the composite scaffolds were found to guide directed tissue infiltration and promote nearby neovascularization when implanted into a subcutaneous model of rats,and the addition of ADSCs further enhanced their adipogenic potential.The presented hybrid manufacturing strategy might provide a promising way to produce additional topological cues within 3D-printed scaffolds for better tissue regeneration.

Local icariin application enhanced periodontal tissue regeneration and relieved local inflammation in a minipig model of periodontitis

Periodontitis is an inflammatory autoimmune disease. Treatment should alleviate inflammation, regulate the immune reaction and promote periodontal tissue regeneration. Icariin is the main active ingredient of Epimedii Folium, and it is a promising compound for the enhancement of mesenchymal stem cell function, promotion of bone formation, inhibition of bone resorption, alleviation of inflammation and regulation of immunity. The study investigated the effect of icariin on periodontal tissue regeneration in a minipig model of periodontitis. The minipig model of periodontitis was established. Icariin was injected locally. The periodontal clinical assessment index, a computed tomography(CT) scan, histopathology and enzyme-linked immune sorbent assay(ELISA)were used to evaluate the effects of icariin. Quantitative analysis results 12 weeks post-injection demonstrated that probing depth,gingival recession, attachment loss and alveolar bone regeneration values were(3.72 ± 1.18) mm vs.(6.56 ± 1.47) mm,(1.67 ± 0.59)mm vs.(2.38 ± 0.61) mm,(5.56 ± 1.29) mm vs.(8.61 ± 1.72) mm, and(25.65 ± 5.13) mm3 vs.(9.48 ± 1.78) mm3 in the icariin group and0.9% NaCl group, respectively. The clinical assessment, CT scan, and histopathology results demonstrated significant enhancement of periodontal tissue regeneration in the icariin group compared to the 0.9% NaCl group. The ELISA results suggested that the concentration of interleukin-1 beta(IL-1β) in the icariin group was downregulated compared to the 0.9% NaCl group, which indicates that local injection of icariin relieved local inflammation in a minipig model of periodontitis. Local injection of icariin promoted periodontal tissue regeneration and exerted anti-inflammatory and immunomodulatory function. These results support the application of icariin for the clinical treatment of periodontitis.

Decellularized adipose matrix provides an inductive microenvironment for stem cells in tissue regeneration

Stem cells play a key role in tissue regeneration due to their self-renewal and multidirectional differentiation,which are continuously regulated by signals from the extracellular matrix(ECM)microenvironment.Therefore,the unique biological and physical characteristics of the ECM are important determinants of stem cell behavior.Although the acellular ECM of specific tissues and organs(such as the skin,heart,cartilage,and lung)can mimic the natural microenvironment required for stem cell differentiation,the lack of donor sources restricts their development.With the rapid development of adipose tissue engineering,decellularized adipose matrix(DAM)has attracted much attention due to its wide range of sources and good regeneration capacity.Protocols for DAM preparation involve various physical,chemical,and biological methods.Different combinations of these methods may have different impacts on the structure and composition of DAM,which in turn interfere with the growth and differentiation of stem cells.This is a narrative review about DAM.We summarize the methods for decellularizing and sterilizing adipose tissue,and the impact of these methods on the biological and physical properties of DAM.In addition,we also analyze the application of different forms of DAM with or without stem cells in tissue regeneration(such as adipose tissue),repair(such as wounds,cartilage,bone,and nerves),in vitro bionic systems,clinical trials,and other disease research.

Application of dental stem cells in three-dimensional tissue regeneration

Dental stem cells can differentiate into different types of cells.Dental pulp stem cells,stem cells from human exfoliated deciduous teeth,periodontal ligament stem cells,stem cells from apical papilla,and dental follicle progenitor cells are five different types of dental stem cells that have been identified during different stages of tooth development.The availability of dental stem cells from discarded or removed teeth makes them promising candidates for tissue engineering.In recent years,three-dimensional(3D)tissue scaffolds have been used to reconstruct and restore different anatomical defects.With rapid advances in 3D tissue engineering,dental stem cells have been used in the regeneration of 3D engineered tissue.This review presents an overview of different types of dental stem cells used in 3D tissue regeneration,which are currently the most common type of stem cells used to treat human tissue conditions.

Possible mechanism of 15D-PGJ2 in promoting periodontal tissue regeneration in patients with mandibular defects

Objective:To explore the main physiological mechanism of 15d-PGJ2 promoting periodontal tissue regeneration in patients with jaw defects caused by periodontal disease.Methods:From February 2016 to July 2019,a controlled study was conducted on 73 healthy residents(healthy group)and 73 patients(case group)with periodontal disease combined with jaw defects in Changsha medical university.T test was used to compare the growth factors of gingival crevicular fluid between the two groups.Peripheral blood cells;Cement-specific protein;Peripheral blood enzyme;Statistical differences in bone metabolites.The t test method compared the content of each index before and after treatment(15d-PGJ2 was treated at a dose of 200 mu/kg for 14 days).The method of factor analysis explores the internal correlation of each index.Result:RANKL,ICAM-1,TGF-β1,Th17,Treg,PDLSCs,SOST,CAP,HMGB1,CTSK,5-LOX,COX-2,NTX were higher in the case group than in the healthy group.In the case group,RANKL,ICAM-1,TGF-β1,Th17,Treg,PDLSCs,SOST,CAP,HMGB1,CTSK,5-LOX,COX-2,NTX were lower than those in the healthy group.The differences between the groups were statistically significant(P<0.05).Compared with before treatment,IL-1β,IL-17,Bfgf,YKL-40,BMP-2,ICTP,PICP,CTX were significantly decreased after treatment.RANKL,ICAM-1,TGF-β1,Th17,Treg,PDLSCs,SOST,CAP,HMGB1,CTSK,5-LOX,COX-2,NTX were significantly increased.The differences were statistically significant(P<0.05).Factor analysis shows that four common factors can be extracted from 21 indicators,and the cumulative contribution rate is 96.993%.Conclusions:The treatment of 15d-PGJ2 in patients with periodontal disease with maxillary defects can significantly affect the expression of multiple characteristic indicators,which may involve four mechanisms:dysregulation of cell differentiation or migration,local inflammation or immune imbalance,destruction of alveolar bone microstructure,load or stimulation,and remodeling.The specific pathway related to this is still to be further explored.

Research progress of strontium in promoting periodontal tissue regeneration

Periodontal disease is a chronic infectious disease of the oral cavity.Its main clinical features are periodontal pocket formation and alveolar bone resorption.Scholars'research hotspot is to achieve periodontal tissue regeneration in patients.Studies have found that strontium has certain potential in promoting periodontal tissue regeneration.In recent years,scholars have been conducting research on strontium and periodontal tissue regeneration,with a view to opening a new path for periodontal disease treatment.This article reviews the research status of strontium and periodontal tissue regeneration.The review results show that strontium can induce the proliferation and differentiation of PDLSCs and promote the regeneration of lost bone tissue;it can inhibit osteoclast activity and induce osteoclast apoptosis through a variety of signaling pathways,thereby inhibiting bone resorption;Promote bone formation;Strontium also has the function of promoting early angiogenesis and suppressing immune inflammatory response.Because the current research on strontium and periodontal tissue regeneration is only focused on in vivo and in vitro experiments,there is no relevant clinical trial to apply strontium to periodontal tissue regeneration.Therefore,if strontium is used to promote periodontal tissue regeneration to achieve the treatment of periodontal disease,further research is needed.

GUIDED TISSUE REGENERATION AROUND DENTAL IMPLANTS IN IMMEDIATE EXTRACTION SOCKETS:COMPARISON OF RESORBABLE ANDNONRESORBABLE MEMBRANES

This study was per formed to compare the efficacy of guided tissue regeneration (GTR) around dentalimplants immediately placed into extraction sockets by resorbable of nonresorbable membranes. Mandibular. P2, P3, and P4 of four aduIt beagle dogs were extracted bilaterally, and buccal standard defects were cre-ated and measured. Eighteen commercially pure titanium Steri-Oss implant fixtures were placed into thefresh extraction sockets. Four implants were untreated controls, four implants received polytetrafluoro-ethylene (e-PTFE, Gore-Tex) membranes, five implants received collagen membranes (ParaGuide), andfive implants received polyglactin 910 mesh (Vicryl). After l4 weeks, clinical measurements were takenand the dogs were sacrificed and all specimens retrieved for histologic and histomorphometric evaluation.The average gain in bone height was 2. 1mm for untreated control sites, 3. 3mm for Gore-Tex sites,3. 8mm for collagen sites, and 1. 3mm for polyglactin 910 sites. The greatest gain in bone height and volume was seen for two sites that received Gore-Tex membranes and remained covered for the entire evalua-tion interval. The results of this study indicate that Gore-Tex and collagen membrane preduced gdri re-sults for GTR around Implants immediately placed into extraction sockets. Since collagen membrane doesnot cause obvious infection and does not need the surgical reentry for membrane removal, it can be a validalternative to Gore-Tex membrane to improve bone regeneration around dental implants, while polyglactin910 mesh seems not suitable to be used as GTR membrane in immediate implantation for its hIgh infectionrate.

Gibberellin promotes cambium reestablishment during secondary vascular tissue regeneration after girdling in an auxin-dependent manner in Populus

Secondary vascular tissue(SVT)development and regeneration are regulated by phytohormones.In this study,we used an in vitro SVT regeneration system to demonstrate that gibberellin(GA)treatment significantly promotes auxin-induced cambium reestablishment.Altering GA content by overexpressing or knocking down ent-kaurene synthase(KS)affected secondary growth and SVT regeneration in poplar.The poplar DELLA gene GIBBERELLIC ACID INSENSITIVE(PtoGAI)is expressed in a specific pattern during secondary growth and cambium regeneration after girdling.Overexpression of PtoGAI disrupted poplar growth and inhibited cambium regeneration,and the inhibition of cambium regeneration could be partially restored by GA application.Further analysis of the PtaDR5:GUS transgenic plants,the localization of PIN-FORMED 1(PIN1)and the expression of auxin-related genes found that an additional GA treatment could enhance the auxin response as well as the expression of PIN1,which mediates auxin transport during SVT regeneration.Taken together,these findings suggest that GA promotes cambium regeneration by stimulating auxin signal transduction.

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.

Targeted delivery of factors and cells for improving cardiac tissue regeneration and heart function following myocardial infarction

Following myocardial infarction(MI),cardiac tissue undergoes irreversible cellular alterations,with cardiomy-ocytes being replaced by fibrotic tissue.In order to improve tissue regeneration,a previously characterized chitosan-based cryogel,which was designed by our group,was used.The treatment regimen involved the sequen-tial delivery of the cryogel loaded with specific cytokines and growth factors,followed by a separate injection of pre-differentiated cells.Initially,the cryogel loaded with interleukin-10 and transforming growth factor-βwas injected into infarcted tissue immediately after MI induction,targeting the acute inflammatory response.On day four post-MI,a second injection was administered,this time utilizing cryogel loaded with vascular endothelial growth factor and fibroblast growth factor-2,aimed at promoting tissue regeneration and angiogenesis.Subse-quently,on day six post-MI,the experimental group received cardiomyocyte-like cells,smooth muscle cells,and endothelial cells.The purpose of these cells,in synergy with cytokines and growth factors,was to repopulate the lost cellular populations,thereby enhancing myocardial repair.The treatment improved myocardial tissue regeneration,increased cardiac output,ejection fraction,and reduced fibrotic regions.Thus,the chitosan-based cryogel,enriched with anti-inflammatory and proangiogenic factors and supplemented with pre-differentiated cells,offers a promising platform for controlled release of therapeutics,promoting substantial tissue repair and regeneration following MI.

Transforming layered 2D mats into multiphasic 3D nanofiber scaffolds with tailored gradient features for tissue regeneration

Multiphasic scaffolds with tailored gradient features hold significant promise for tissue regeneration applications. Herein, this work reports the transformation of two-dimensional (2D) layered fiber mats into three-dimensional (3D) multiphasic scaffolds using a ‘solids-of-revolution’ inspired gas-foaming expansion technology. These scaffolds feature precise control over fiber alignment, pore size, and regional structure. Manipulating nanofiber mat layers and Pluronic F127 concentrations allows further customization of pore size and fiber alignment within different scaffold regions. The cellular response to multiphasic scaffolds demonstrates that the number of cells migrated and proliferated onto the scaffolds is mainly dependent on the pore size rather than fiber alignment. In vivo subcutaneous implantation of multiphasic scaffolds to rats reveals substantial cell infiltration, neo tissue formation, collagen deposition, and new vessel formation within scaffolds, greatly surpassing the capabilities of traditional nanofiber mats. Histological examination indicates the importance of optimizing pore size and fiber alignment for the promotion of cell infiltration and tissue regeneration. Overall, these scaffolds have potential applications in tissue modeling, studying tissue-tissue interactions, interface tissue engineering, and highthroughput screening for optimized tissue regeneration.

The use of hydrogel microspheres as cell and drug delivery carriers for bone,cartilage,and soft tissue regeneration

Bone,cartilage,and soft tissue regeneration is a complex process involving many cellular activities across various cell types.Autografts remain the“gold standard”for the regeneration of these tissues.However,the use of autografts is associated with many disadvantages,including donor scarcity,the requirement of multiple surgeries,and the risk of infection.The development of tissue engineering techniques opens new avenues for enhanced tissue regeneration.Nowadays,the expectations of tissue engineering scaffolds have gone beyond merely providing physical support for cell attachment.Ideal scaffolds should also provide biological cues to actively boost tissue regeneration.As a new type of injectable biomaterial,hydrogel microspheres have been increasingly recognised as promising therapeutic carriers for the local delivery of cells and drugs to enhance tissue regeneration.Compared to traditional tissue engineering scaffolds and bulk hydrogel,hydrogel microspheres possess distinct advantages,including less invasive delivery,larger surface area,higher transparency for visualisation,and greater flexibility for functionalisation.Herein,we review the materials characteristics of hydrogel microspheres and compare their fabrication approaches,including microfluidics,batch emulsion,electrohydrodynamic spraying,lithography,and mechanical fragmentation.Additionally,based on the different requirements for bone,cartilage,nerve,skin,and muscle tissue regeneration,we summarize the applications of hydrogel microspheres as cell and drug delivery carriers for the regeneration of these tissues.Overall,hydrogel microspheres are regarded as effective therapeutic delivery carriers to enhance tissue regeneration in regenerative medicine.However,significant effort is required before hydrogel microspheres become widely accepted as commercial products for clinical use.

Going below and beyond the surface: Microneedle structure, materials, drugs, fabrication, and applications for wound healing and tissue regeneration

Microneedle, as a novel drug delivery system, has attracted widespread attention due to its non-invasiveness, painless and simple administration, controllable drug delivery, and diverse cargo loading capacity. Although microneedles are initially designed to penetrate stratum corneum of skin for transdermal drug delivery, they, recently, have been used to promote wound healing and regeneration of diverse tissues and organs and the results are promising. Despite there are reviews about microneedles, few of them focus on wound healing and tissue regeneration. Here, we review the recent advances of microneedles in this field. We first give an overview of microneedle system in terms of its potential cargos (e.g., small molecules, macromolecules, nucleic acids, nanoparticles, extracellular vesicle, cells), structural designs (e.g., multidrug structures, adhesive structures), material selection, and drug release mechanisms. Then we briefly summarize different microneedle fabrication methods, including their advantages and limitations. We finally summarize the recent progress of microneedle-assisted wound healing and tissue regeneration (e.g., skin, cardiac, bone, tendon, ocular, vascular, oral, hair, spinal cord, and uterine tissues). We expect that our article would serve as a guideline for readers to design their microneedle systems according to different applications, including material selection, drug selection, and structure design, for achieving better healing and regeneration efficacy.

Highly resilient and fatigue-resistant poly(4-methyl-ε-caprolactone)porous scaffold fabricated via thiol-yne photo-crosslinking/salt-templating for soft tissue regeneration

Elastomeric scaffolds, individually customized to mimic the structural and mechanical properties of natural tissues have been used for tissue regeneration. In this regard, polyester elastic scaffolds with tunable mechanical properties and exceptional biological properties have been reported to provide mechanical support and structural integrity for tissue repair. Herein, poly(4-methyl-ε-caprolactone) (PMCL) was first double-terminated by alkynylation (PMCL-DY) as a liquid precursor at room temperature. Subsequently, three-dimensional porous scaffolds with custom shapes were fabricated from PMCL-DY via thiol-yne photocrosslinking using a practical salt template method. By manipulating the Mn of the precursor, the modulus of compression of the scaffold was easily adjusted. As evidenced by the complete recovery from 90% compression, the rapid recovery rate of >500 mm min 1, the extremely low energy loss coefficient of <0.1, and the superior fatigue resistance, the PMCL20-DY porous scaffold was confirmed to harbor excellent elastic properties. In addition, the high resilience of the scaffold was confirmed to endow it with a minimally invasive application potential. In vitro testing revealed that the 3D porous scaffold was biocompatible with rat bone marrow stromal cells (BMSCs), inducing BMSCs to differentiate into chondrogenic cells. In addition, the elastic porous scaffold demonstrated good regenerative efficiency in a 12-week rabbit cartilage defect model. Thus, the novel polyester scaffold with adaptable mechanical properties may have extensive applications in soft tissue regeneration.

3D printing of cell-delivery scaffolds for tissue regeneration Jianmin Xue and others

Tissue engineering strategy that combine biomaterials with living cells has shown special advantages in tissue regeneration and promoted the development of regenerative medicine.In particular,the rising of 3D printing technology further enriched the structural design and composition of tissue engineering scaffolds,which also provided convenience for cell loading and cell delivery of living cells.In this review,two types of cell-delivery scaffolds for tissue regeneration,including 3D printed scaffolds with subsequent cell-seeding and 3D cells bioprinted scaffolds,are mainly reviewed.We devote a major part to present and discuss the recent advances of two 3D printed cell-delivery scaffolds in regeneration of various tissues,involving bone,cartilage,skin tissues etc.Although two types of 3D printed cell-delivery scaffolds have some shortcomings,they do have generally facilitated the exploration of tissue engineering scaffolds in multiple tissue regeneration.It is expected that 3D printed cell-delivery scaffolds will be further explored in function mechanism of seeding cells in vivo,precise mimicking of complex tissues and even organ reconstruction under the cooperation of multiple fields in future.

Novel metal nanomaterials to promote angiogenesis in tissue regeneration

Angiogenesis-the formation of new blood vessels from existing blood vessels-has drawn significant attention in medical research.New techniques have been developed to control proangiogenic factors to obtain desired ef-fects.Two important research areas are 1)understanding cellular mechanisms and signaling pathways involved in angiogenesis and 2)discovering new biomaterials and nanomaterials with proangiogenic effects.This paper reviews recent developments in controlling angiogenesis in the context of regenerative medicine and wound healing.We focus on novel proangiogenic materials that will advance the field of regenerative medicine.Specifically,we mainly focus on metal nanomaterials.We also discuss novel technologies developed to carry these proangio-genic inorganic molecules efficiently to target sites.We offer a comprehensive overview by combining existing knowledge regarding metal nanomaterials with novel developments that are still being refined to identify new nanomaterials.

Interplay between mesenchymal stem cells and macrophages:Promoting bone tissue repair

The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.

Exhausted local lactate accumulation via injectable nanozyme-functionalized hydrogel microsphere for inflammation relief and tissue regeneration

Local lactate accumulation greatly hinders tissue repair and regeneration under ischemic condition.Herein,an injectable microsphere(MS@MCL)for local lactate exhaustion was constructed by grafting manganese dioxide(MnO_(2))-lactate oxidase(LOX)composite nanozyme on microfluidic hyaluronic acid methacrylate(HAMA)microspheres via chemical bonds,achieving a long-term oxygen-promoted lactate exhaustion effect and a long half-life in vivo.The uniform and porous microspheres synthesized by microfluidic technology is beneficial to in situ injection therapy and improving encapsulation efficiency.Furthermore,chemical grafting into HAMA microspheres through amide reactions promoted local enzymatic concentration and activity enhancement.It was showed that the MS@MCL eliminated oxidative and inflammatory stress and promoted extracellular matrix metabolism and cell survival when co-cultured with nucleus pulposus cells(NPCs)in vitro.In the rat degenerative intervertebral disc model caused by lactate injection,MS@MCL showed a long-term therapeutic effect in reducing intervertebral height narrowing and preventing extracellular matrix(ECM)degradation as well as inflammatory damage in vivo.Altogether,this study confirms that this nanozyme-functionalized injectable MS@MCL effectively improves the regenerative and reparative effect in ischemic tissues by disposing of enriched lactate in local microenvironment.

Dimethyloxallyl glycine/nanosilicates-loaded osteogenic/angiogenic difunctional fibrous structure for functional periodontal tissue regeneration

The coupled process of osteogenesis-angiogenesis plays a crucial role in periodontal tissue regeneration.Although various cytokines or chemokines have been widely applied in periodontal in situ tissue engineering,most of them are macromolecular proteins with the drawbacks of short effective half-life,poor stability and high cost,which constrain their clinical translation.Our study aimed to develop a difunctional structure for periodontal tissue regeneration by incorporating an angiogenic small molecule,dimethyloxalylglycine(DMOG),and an osteoinductive inorganic nanomaterial,nanosilicate(nSi)into poly(lactic-co-glycolic acid)(PLGA)fibers by electrospinning.The physiochemical properties of DMOG/nSi-PLGA fibrous membranes were characterized.Thereafter,the effect of DMOG/nSi-PLGA membranes on periodontal tissue regeneration was evaluated by detecting osteogenic and angiogenic differentiation potential of periodontal ligament stem cells(PDLSCs)in vitro.Additionally,the fibrous membranes were transplanted into rat periodontal defects,and tissue regeneration was assessed with histological evaluation,micro-computed tomography(micro-CT),and immunohistochemical analysis.DMOG/nSi-PLGA membranes possessed preferable mechanical property and biocompatibility.PDLSCs seeded on the DMOG/nSi-PLGA membranes showed up-regulated expression of osteogenic and angiogenic markers,higher alkaline phosphatase(ALP)activity,and more tube formation in comparison with single application.Further,in vivo study showed that the DMOG/nSi-PLGA membranes promoted recruitment of CD90+/CD34stromal cells,induced angiogenesis and osteogenesis,and regenerated cementum-ligament-bone complex in periodontal defects.Consequently,the combination of DMOG and nSi exerted admirable effects on periodontal tissue regeneration.DMOG/nSi-PLGA fibrous membranes could enhance and orchestrate osteogenesis-angiogenesis,and may have the potential to be translated as an effective scaffold in periodontal tissue engineering.