Vascular Endothelial Growth Factor‑Recruiting Nanofiber Bandages Promote Multifunctional Skin Regeneration via Improved Angiogenesis and Immunomodulation

Tissue injury leads to gradients of chemoattractants,which drive multiple processes for tissue repair,including the inflam-matory response as well as endogenous cell recruitment.However,a limited time window for the gradients of chemoattract-ants as well as their poor stability at the injury site may not translate into healthy tissue repair.Consequently,intelligent multifunctional scaffolds with the capability to stabilize injury-induced cytokines and chemokines hold great promise for tissue repair.Vascular endothelial growth factor(VEGF)plays a significant role in wound healing by promoting angiogen-esis.The overarching objective of this research was to develop intelligent multifunctional scaffolds with the capability to endogenously recruit VEGF and promote wound healing via angiogenic and immunomodulatory dual functions.Prominin-1-derived peptide(PR1P)was encapsulated into electrospun poly(L-lactide-coglycolide)/gelatin(P/G)-based bandages.The sustained release of PR1P recruited VEGF in situ,thereby stabilizing the protein concentration peak in vivo and affording a reparative microenvironment with an adequate angiogenic ability at the wound site.Meanwhile,PR1P-recruited VEGF-induced macrophage reprogramming towards M2-like phenotypes further conferred immunomodulatory functions to the bandages.These dual functions of proangiogenesis and immunomodulation formed a cascade amplification,which regulated matrix metalloproteinases(MMP-9)as well as inflammatory factors(nuclear factor(NF)-κb,tumor necrosis factor(TNF)-α)in the wound microenvironment via the VEGF/macrophages/microenvironment axis.Consequently,the bandages realized multifunctional regeneration in splinted excisional wounds in rats,with or without diabetes,affording a higher skin append-age neogenesis,sensory function,and collagen remodeling.Conclusively,our approach encompassing in situ recruitment of VEGF at the injury site with the capability to promote immunomodulation-mediated tissue repair affords a promising avenue for scarless wound regeneration,which may also have implications for other tissue engineering disciplines.

Correction to:Vascular Endothelial Growth Factor‑Recruiting Nanofiber Bandages Promote Multifunctional Skin Regeneration via Improved Angiogenesis and Immunomodulation

Correction to:Advanced Fiber Materials https://doi.org/10.1007/s42765-022-00226-8 In this article the author name Muhammad Shafiq was incorrectly written as Shafiq Muhammad.The original article has been corrected.

Multifunctional bioactive core-shell electrospun membrane capable to terminate inflammatory cycle and promote angiogenesis in diabetic wound

Diabetic wound(DW)healing is a major clinical challenge due to multifactorial complications leading to prolonged inflammation.Electrospun nanofibrous(NF)membranes,due to special structural features,are promising biomaterials capable to promote DW healing through the delivery of active agents in a controlled manner.Herein,we report a multifunctional composite NF membrane loaded with ZnO nanoparticles(NP)and oregano essential oil(OEO),employing a new loading strategy,capable to sustainedly co-deliver bioactive agents.Physicochemical characterization revealed the successful fabrication of loaded nanofibers with strong in vitro anti-bacterial and anti-oxidant activities.Furthermore,in vivo wound healing confirmed the potential of bioactive NF membranes in epithelialization and granulation tissue formation.The angiogenesis was greatly prompted by the bioactive NF membranes through expression of vascular endothelial growth factor(VEGF).Moreover,the proposed NF membrane successfully terminated the inflammatory cycle by downregulating the pro-inflammatory cytokines interleukin6(IL-6)and matrix metalloproteinases-9(MMP-9).In vitro and in vivo studies revealed the proposed NF membrane is a promising dressing material for the healing of DW.

Electrospun silk fibroin/poly(L-lactide-ecaplacton)graft with platelet-rich growth factor for inducing smooth muscle cell growth and infiltration

The construction of a smooth muscle layer for blood vessel through electrospinning method plays a key role in vascular tissue engineering.However,smooth muscle cells(SMCs)penetration into the electrospun graft to form a smooth muscle layer is limited due to the dense packing of fibers and lack of inducing factors.In this paper,silk fibroin/poly(L-lactide-e-caplacton)(SF/PLLA-CL)vascular graft loaded with platelet-rich growth factor(PRGF)was fabricated by electrospinning.The in vitro results showed that SMCs cultured in the graft grew fast,and the incorporation of PRGF could induce deeper SMCs infiltrating compared to the SF/PLLA-CL graft alone.Mechanical properties measurement showed that PRGF-incorporated graft had proper tensile stress,suture retention strength,burst pressure and compliance which could match the demand of native blood vessel.The success in the fabrication of PRGF-incorporated SF/PLLA-CL graft to induce fast SMCs growth and their strong penetration into graft has important application for tissue-engineered blood vessels.

Photothermal‑Triggered Structural Change of Nanofiber Scaffold Integrating with Graded Mineralization to Promote Tendon–Bone Healing

Scaffolds functionalized with graded changes in both fiber alignment and mineral content are more appealing for tendon-bone healing.This study reports the healing of rotator cuff injury using a heterogeneous nanofiber scaffold,which is associated with a structural gradating from aligned to random and an increasing gradient of mineral content in the same orientation.The photothermal-triggered structural change of a nanofiber scaffold followed by graded mineralization is key to constructing such scaffolds.This type of scaffold was found to be biocompatible and provide beneficial contact guidance in the manipulation of tendon-derived stem cell morphologies in vitro.Specifically,tenogenic and osteogenic differentiation of tendon-derived stem cells were simultaneously achieved using the fabricated scaffold.In vivo investigation also showed the improved healing of rabbit rotator cuff injuries based on immunohistochemical analysis and biomechanical investigation that indicates the promising potential of a dual-gradient nanofiber scaffold in clinical tendon-bone healing.

Advanced fabrication for electrospun three-dimensional nanofiber aerogels and scaffolds

Electrospinning is a versatile strategy for creating nanofiber materials with various structures,which has broad application for a myriad of areas ranging from tissue engineering,energy harvesting,filtration and has become one of the most important academic and technical activities in the field of material science in recent years.In addition to playing a significant role in the construction of two-dimensional(2D)nanomaterials,electrospinning holds great promise as a robust method for producing three-dimensional(3D)aerogels and scaffolds.This article reviews and summarizes the recent advanced methods for fabricating electrospun three-dimensional nanofiber aerogels and scaffolds,including gas foaming,direct electrospinning of 3D nanofibrous scaffold,short nanofibers assembling into 3D aerogels/scaffolds,3D printing,electrospray,origami and cell sheet engineering,centrifugal electrospinning,and other methods.Besides,intriguing formation process,crosslinking pathway,properties,and applications of 3D aerogels and scaffolds are also introduced.Taken together,these aerogels and scaffolds with various excellent features present tremendous potential in various fields.

Electrospinning nanofiber scaffolds for soft and hard tissue regeneration

Tissue engineering is an interdisciplinary field that integrates medical,biological,and engineering expertise to restore or regenerate the functionality of healthy tissues and organs.The three fundamental pillars of tissue engineering are scaffolds,cells,and biomolecules.Electrospun nanofibers have been successfully used as scaffolds for a variety of tissue engineering applications because they are biomimetic of the natural,fibrous extracellular matrix(ECM)and contain a three-dimensional(3D)network of interconnected pores.In this review,we provide an overview of the electrospinning process,its principles,and the application of the resultant electrospun nanofibers for tissue engineering.We first briefly introduce the electrospinning process and then cover its principles and standard equipment for biomaterial fabrication.Next,we highlight the most important and recent advances related to the applications of electrospun nanofibers in tissue engineering,including skin,blood vessels,nerves,bone,cartilage,and tendon/ligament applications.Finally,we conclude with current advancements in the fabrication of electrospun nanofiber scaffolds and their biomedical applications in emerging areas.

In vitro evaluation of electrospun gelatin-glutaraldehyde nanofibers

The gelatin-glutaraldehyde （gelatin-GA） nanofibers were electrospun in order to overcome the defects of ex-situ crosslinking process such as complex process, destruction of fiber morphology and decrease of porosity. The morphological structure, porosity, thermal property, moisture absorption and moisture retention performance, hydrolytic resistance, mechanical property and biocompatibiUty of nanofiber scaffolds were tested and characterized. The gelatin-GA nanofiber has nice uniform diameter and more than 80% porosity. The hydrolytic resistance and mechanical property of the gelatin-GA nanofiber scaffolds are greatly improved compared with that of gelatin nanofibers. The contact angle, moisture absorption, hydrolysis resistance, thermal resistance and mechanical property of gelatin-GA nanofiber scaffolds could be adjustable by varying the gelatin solution concentration and GA content. The gelatin- GA nanofibers had excellent properties, which are expected to be an ideal scaffold for biomedical and tissue engineering applications.

A 3D-Bioprinted dual growth factor-releasing intervertebral disc scaffold induces nucleus pulposus and annulus fibrosus reconstruction

Regeneration of Intervertebral disc(IVD)is a scientific challenge because of the complex structure and composition of tissue,as well as the difficulty in achieving bionic function.Here,an anatomically correct IVD scaffold composed of biomaterials,cells,and growth factors were fabricated via three-dimensional(3D)bioprinting technology.Connective tissue growth factor(CTGF)and transforming growth factor-β3(TGF-β3)were loaded onto polydopamine nanoparticles,which were mixed with bone marrow mesenchymal stem cells(BMSCs)for regenerating and simulating the structure and function of the nucleus pulposus and annular fibrosus.In vitro experiments confirmed that CTGF and TGF-β3 could be released from the IVD scaffold in a spatially controlled manner,and induced the corresponding BMSCs to differentiate into nucleus pulposus like cells and annulus fibrosus like cells.Next,the fabricated IVD scaffold was implanted into the dorsum subcutaneous of nude mice.The reconstructed IVD exhibited a zone-specific matrix that displayed the corresponding histological and immunological phenotypes:primarily type II collagen and glycosaminoglycan in the core zone,and type I collagen in the surrounding zone.The testing results demonstrated that it exhibited good biomechanical function of the reconstructed IVD.The results presented herein reveal the clinical application potential of the dual growth factors-releasing IVD scaffold fabricated via 3D bioprinting.However,the evaluation in large mammal animal models needs to be further studied.

Electrodeposition of calcium phosphate onto polyethylene terephthalate artificial ligament enhances graft-bone integration after anterior cruciate ligament reconstruction

It is a big challenge to develop a polyethylene terephthalate(PET)artificial ligament with excellent osteogenetic activity to enhance graft-bone integration for ligament reconstruction.Herein,we evaluated the effect of biomineralization(BM)and electrodeposition(ED)method for depositing calcium-phosphate(CaP)on the PET artificial ligament in vitro and in vivo.Scanning electron microscopy and energy-dispersive X-Ray spectrometer mapping analysis revealed that the ED-CaP had more uniform particles and element distribution(Ca,P and O),and thermogravimetric analysis showed there were more CaP on the PET/ED-CaP than the PET/BM-CaP scaffold.Moreover,the hydrophilicity of PET scaffolds was significantly improved after CaP deposition.In vitro study showed that CaP coating via BM or ED method could improve the attachment and proliferation of MC3T3-E1 cells,and ED-CaP coating significantly increased osteogenic differentiation of the cells,in which the Wnt/β-catenin signaling pathway might be involved.In addition,radiological,histological and immunohistochemical results of in vivo study in a rabbit anterior cruciate ligament(ACL)reconstruction model demonstrated that the PET/BM-CaP and PET/ED-CaP scaffolds significantly improved graft-bone integration process compared to the PET scaffold.More importantly,larger areas of new bone ingrowth and the formation of fibrocartilage tissue were observed at 12 weeks in the PET/ED-CaP group,and the biomechanical tests showed increased ultimate failure load and stiffness in PET/ED-CaP group compared to PET/BM-CaP and PET group.Therefore,ED of CaP is an effective strategy for the modification of PET artificial ligament and can enhance graft-bone integration both in vitro and in vivo.

Stem cell homing-based tissue engineering using bioactive materials

Tissue engineering focuses on repairing tissue and restoring tissue functions by employing three elements： scaffolds, cells and biochemical signals. In tissue engineering, bioactive material scaffolds have been used to cure tissue and organ defects with stem cell-based therapies being one of the best documented approaches. In the review, different biomaterials which are used in several methods to fabricate tissue engineering scaffolds were explained and show good properties （biocompatibility, biodegradability, and mechanical properties etc.） for cell migration and infiltration. Stem cell homing is a recruitment process for inducing the migration of the systemically transplanted cells, or host cells, to defect sites. The mechanisms and modes of stem cell homing-based tissue engineering can be divided into two types depending on the source of the stem cells： endogenous and exogenous. Exogenous stem cell-based bioactive scaffolds have the challenge of long-term culturing in vitro and for endogenous stem cells the biochemical signal homing recruitment mechanism is not clear yet. Although the stem cell homing-based bioactive scaffolds are attractive candidates for tissue defect therapies, based on in vitro studies and animal tests, there is still a long way before clinical application.

Electrospinning:An emerging technology to construct polymer-based nanofibrous scaffolds for diabetic wound healing

A chronic wound in diabetic patients is a major public health concern withsocioeconomic and clinical manifestations.The underlying medical condition of diabeticpatients deteriorates the wound through physiological,metabolic,molecular,and cellularpathologies.Consequently,a wound enters a vicious pathological inflammatory cycle.Many therapeutic approaches are in practice to manage diabetic wounds hence ensuringthe regeneration process.Polymer-based biomaterials have come up with hightherapeutic promises.Many efforts have been devoted,over the years,to build aneffective wound healing material using polymers.The electrospinning technique,although not new,has turned out to be one of the most effective strategies in buildingwound healing biomaterials due to the special structural advantages of electrospunnanofibers over the other formulations.In this review,careful integration of allelectrospinning approaches has been presented which will not only give an insight intothe current updates but also be helpful in the development of new therapeutic materialconsidering pathophysiological conditions of a diabetic wound.

Fabrication and characterization of Antheraea pernyi silk fibroin-blended P（LLA-CL） nanofibrous scaffolds for peripheral nerve tissue engineering

Electrospun nanofibers have gained widespreading interest for tissue engineering application. In the present study, ApF/P（LLA-CL） nanofibrous scaffolds were fabricated via electrospinning. The feasibility of the material as tissue engineering nerve scaffold was investigated in vitro. The average diameter increased with decreasing the blend ratio of ApF to P（LLA-CL）. Characterization of 13C NMR and FTIR clarified that there is no obvious chemical bond reaction between ApF and P（LLA-CL）. The tensile strength and elongation at break increased with the content increase of P（LLA-CL）. The surface hydrophilic property of nanofibrous scaffolds enhanced with the increased content of ApF. Cell viability studies with Schwann cells demonstrated that ApFIP（LLA-CL） blended nanofibrous scaffolds significantly promoted cell growth as compare to P（LLA-CL）, especially when the weight ratio of ApF to P（LLA-CL） was 25：75. The present work provides a basis for further studies of this novel nanofibrous material （ApF/P（LLA-CL）） in peripheral nerve tissue repair or regeneration.

Recent Advancements on Three‑Dimensional Electrospun Nanofiber Scaffolds for Tissue Engineering

Electrospinning is widely accepted as a technique for the fabrication of nanofibrous three-dimensional(3D)scaffolds which mimic extracellular matrix(ECM)microenvironment for tissue engineering(TE).Unlike normal densely-packed two-dimensional(2D)nanofibrous membranes,3D electrospun nanofiber scaffolds are dedicated to more precise spatial control,endowing the scaffolds with a sufficient porosity and 3D environment similar to the in vivo settings as well as optimizing the properties,including injectability,compressibility,and bioactivity.Moreover,the 3D morphology regulates cellular interaction and mediates growth,migration,and differentiation of cell for matrix remodeling.The variation among scaffold structures,functions and applications depends on the selection of electrospinning materials and methods as well as on the post-processing of electrospun scaffolds.This review summarizes the recent new forms for building electrospun 3D nanofiber scaffolds for TE applications.A variety of approaches aimed at the fabrication of 3D electrospun scaffolds,such as multilay-ering electrospinning,sacrificial agent electrospinning,wet electrospinning,ultrasound-enhanced electrospinning as well as post-processing techniques,including gas foaming,ultrasonication,short fiber assembly,3D printing,electrospraying,and so on are discussed,along with their advantages,limitations and applications.Meanwhile,the current challenges and prospects of 3D electrospun scaffolds are rationally discussed,providing an insight into developing the vibrant fields of biomedicine.

The comparison of the Wnt signaling pathway inhibitor delivered electrospun nanoyarn fabricated with two methods for the application of urethroplasty

Urethral strictures were common disease caused by over-expression of extracellular matrix from fibroblast. In this study, we compare two nanoyarn scaffolds for improving fibroblasts infiltration without inhibition the over-expression of extracellular matrix. Collagenlpoly（L-lactide-co-caprolactone）（ColIP（LLA-CL）） nanoyarn scaffolds were prepared by conjugated electrospinning and dynamic liquid electrospinning, respectively, in addition, co-axial electrospinning technique was combined with the nanoyarn fabrication process to produce nanoyarn scaffolds loading Wntsignaling pathway inhibitor. The mechanical properties of the scaffolds were examined and morphology was observed by SEM. Cell morphology, proliferation and infiltration on the scaffolds were investigated by SEM, MTT assay and H＆E staining, respectively. The release profiles of different scaffolds were determined using HPLC. The results indicated that cells showed an organized morphology along the nanoyarns and considerable infiltration into the nanoyarn scaffolds prepared by dynamic liquid electrospinning （DLY）. It was also observed that the DLY significantly facilitate cell proliferation. The D-DLY could facilitate the infiltration of the fibroblasts and could be a promising scaffold for the treatment of urethra stricture while it may inhibit the collagen production.

Evaluation of hydrogels for soft tissue adhesives in vitro and in vivo analyses

In this study, natural materials （sodium alginate, dextran, gelatin and carboxymethyl chitosan） were modified to get aldehyde components and amino components. Upon mixing the two-component solutions together, four kinds of Schiff base hydrogels formed successfully within 5-300 s and could seal the wound tissue. The cytotoxicity tests of hydrogel extraction solution confirmed that the hydrogels are nontoxic materials. The adhesive ability was evaluated in vivo by measuring the adhesive strength after sealing the skin incisions on the back of rats. All the hydrogels showed higher adhesive strength than that of commercial fibrin glue and the blank control. The histological staining observation by hematoxylin and eosin staining （HE） and Masson＇s trichrome staining （MTC） methods suggested that the hydrogels had good biocompatibility and biodegradation in vivo. They have only normal initial inflammation to skin tissue and could improve the formation of new collagen in the incision section. So, the prepared hydrogels were both safe and effective tissue adhesive, which had the great potentials to be used as skin tissue adhesive.

Extracellular matrix and nitric oxide based functional coatings for vascular stents

Cardiovascular diseases cause huge morbidity and mortality worldwide.Recently,vascular stents have been most frequently used to treat cardiovascular diseases thanks to their effectiveness at dilating blood vessels and main-taining the circulation of blood.However,stent expansion leads to endothelium injury posing thrombogenic and in-stent restenosis(ISR).In addition,the bioinertness and an acute lack of endothelium-like function on the surface of implanted vascular stents compromise their performance.Functional coatings of vascular stents to mimic endothelium-and extracellular matrix(ECM)-like functions could prevent thrombosis,inhibit the over-growth of smooth muscle cells(SMCs),and promote the rapid restoration of native endothelium,hence effec-tively suppressing stent-related complications.Noticeably,ECM-based coatings including a multitude of bioactive molecular,such as growth factors,heparin,hyaluronic acid(HA)and so on,have been proven to play important effects on regulating ECs/SMCs behavior and improving blood compatibility of stents.Additionally,nitric oxide(NO),which is fundamental to the endothelium-mediated anti-thrombogenesity,anti-intimal hyperplasia and anti-inflammation,has been leveraged to improve vascular stent functions.Therefore,this review will highlight different strategies and biological role of ECM and NO based functional coatings on vascular stent.Lastly,some potential important factors for stents development are suggested as well.