Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration.

Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.

Macrophages in guided bone regeneration: potential roles and future directions.

Guided bone regeneration (GBR) is one of the most widely used and thoroughly documented alveolar bone augmentation surgeries. However, implanting GBR membranes inevitably triggers an immune response, which can lead to inflammation and failure of bone augmentation. It has been shown that GBR membranes may significantly improve in vivo outcomes as potent immunomodulators, rather than solely serving as traditional barriers. Macrophages play crucial roles in immune responses and participate in the entire process of bone injury repair. The significant diversity and high plasticity of macrophages complicate our understanding of the immunomodulatory mechanisms underlying GBR. This review provides a comprehensive summary of recent findings on the potential role of macrophages in GBR for bone defects in situ. Specifically, macrophages can promote osteogenesis or fibrous tissue formation in bone defects and degradation or fibrous encapsulation of membranes. Moreover, GBR membranes can influence the recruitment and polarization of macrophages. Therefore, immunomodulating GBR membranes are primarily developed by improving macrophage recruitment and aggregation as well as regulating macrophage polarization. However, certain challenges remain to be addressed in the future. For example, developing more rational and sophisticated sequential delivery systems for macrophage activation reagents; addressing the interference of bone graft materials and dental implants; and understanding the correlations among membrane degradation, macrophage responses, and bone regeneration.

Osteoinductive micro-nano guided bone regeneration membrane for in situ bone defect repair.

BACKGROUND: Biomaterials used in bone tissue engineering must fulfill the requirements of osteoconduction, osteoinduction, and osseointegration. However, biomaterials with good osteoconductive properties face several challenges, including inadequate vascularization, limited osteoinduction and barrier ability, as well as the potential to trigger immune and inflammatory responses. Therefore, there is an urgent need to develop guided bone regeneration membranes as a crucial component of tissue engineering strategies for repairing bone defects. METHODS: The mZIF-8/PLA membrane was prepared using electrospinning technology and simulated body fluid external mineralization method. Its ability to induce biomimetic mineralization was evaluated through TEM, EDS, XRD, FT-IR, zeta potential, and wettability techniques. The biocompatibility, osteoinduction properties, and osteo-immunomodulatory effects of the mZIF-8/PLA membrane were comprehensively evaluated by examining cell behaviors of surface-seeded BMSCs and macrophages, as well as the regulation of cellular genes and protein levels using PCR and WB. In vivo, the mZIF-8/PLA membrane's potential to promote bone regeneration and angiogenesis was assessed through Micro-CT and immunohistochemical staining. RESULTS: The mineralized deposition enhances hydrophilicity and cell compatibility of mZIF-8/PLA membrane. mZIF-8/PLA membrane promotes up-regulation of osteogenesis and angiogenesis related factors in BMSCs. Moreover, it induces the polarization of macrophages towards the M2 phenotype and modulates the local immune microenvironment. After 4-weeks of implantation, the mZIF-8/PLA membrane successfully bridges critical bone defects and almost completely repairs the defect area after 12-weeks, while significantly improving the strength and vascularization of new bone. CONCLUSIONS: The mZIF-8/PLA membrane with dual osteoconductive and immunomodulatory abilities could pave new research paths for bone tissue engineering.

A Janus, robust, biodegradable bacterial cellulose/Ti3C2Tx MXene bilayer membranes for guided bone regeneration.

Guided bone regeneration (GBR) stands as an essential modality for craniomaxillofacial bone defect repair, yet challenges like mechanical weakness, inappropriate degradability, limited bioactivity, and intricate manufacturing of GBR membranes hindered the clinical efficacy. Herein, we developed a Janus bacterial cellulose(BC)/MXene membrane through a facile vacuum filtration and etching strategy. This Janus membrane displayed an asymmetric bilayer structure with interfacial compatibility, where the dense layer impeded cell invasion and the porous layer maintained stable space for osteogenesis. Incorporating BC with Ti3C2Tx MXene significantly enhanced the mechanical robustness and flexibility of the material, enabling clinical operability and lasting GBR membrane supports. It also contributed to a suitable biodegradation rate, which aligned with the long-term bone repair period. After demonstrating the desirable biocompatibility, barrier role, and osteogenic capability in vitro, the membrane's regenerative potential was also confirmed in a rat cranial defect model. The excellent bone repair performance could be attributed to the osteogenic capability of MXene nanosheets, the morphological cues of the porous layer, as well as the long-lasting, stable regeneration space provided by the GBR membrane. Thus, our work presented a facile, robust, long-lasting, and biodegradable BC/MXene GBR membrane, offering a practical solution to craniomaxillofacial bone defect repair.

Biodegradable polyvinyl alcohol/nano-hydroxyapatite composite membrane enhanced by MXene nanosheets for guided bone regeneration.

MXene, as a new category of two-dimensional nanomaterials, exhibits a promising prospect in biomedical applications due to its ultrathin structure and morphology, as well as a range of remarkable properties such as biological, chemical, electronic, and optical properties. In this work, different concentrations of MXene (M) were added to polyvinyl alcohol (PVA, P)/nano-hydroxyapatite (n-HA, H) mixed solution, and series of PVA/n-HA/MXene (PHM) composite membranes were obtained by combining sol-gel and freeze-drying processes. Morphology, chemical composition, surface, and mechanical properties of the prepared PHM membranes were characterized by various techniques. Subsequently, the swelling and degradation performances of the composite membranes were tested by swelling and degradation tests. In addition, in vitro studies like cell adhesion, cytotoxicity, proliferation, osteogenic differentiation, and antibacterial properties of MC3T3-E1 were also evaluated. The results showed that the addition of MXene could apparently improve the composite membranes' physicochemical properties, bioactivity, and osteogenic differentiation. Specially, PHM membrane had the best comprehensive properties when the concentration of MXene was set as 2.0% w/v. In a word, the addition of MXene has a positive effect on improving the mechanical properties, osteogenic induction, and antibacterial properties of PH composite membranes, and the prepared PHM composite membranes possess potential applications for guided bone regeneration.

Functionalizable bacterial cellulose composite membrane for guided tissue regeneration.

This research aims to develop guided tissue regeneration (GTR) membranes from bacterial cellulose (BC), a natural polysaccharide-based biopolymer. A double-layered BC composite membrane was prepared by coating the BC membrane with mixed carboxymethyl cellulose/poly(ethylene oxide) (CMC/PEO) fibers via electrospinning. The CMC/PEO-BC membranes were then characterized for their chemical and physical characteristics. The 8 % (wt/v) CMC/PEO (1:1) aqueous solution yielded well-defined electrospun CMC/PEO nanofibers (125 ± 10 nm) without beads. The CMC/PEO-BC membranes exhibited good mechanical and swelling properties as well as good cytocompatibility against human periodontal ligament cells (hPDLs). Its functionalizability via carboxyl entities in CMC was tested using the calcium-binding domain of plant-derived recombinant human osteopontin (p-rhOPN-C122). As evaluated by enzyme-linked immunosorbent assay, a 98-99 % immobilization efficiency was achieved in a concentration-dependent manner over an applied p-rhOPN-C122 concentration range of 7.5-30 ng/mL. The biological function of the membrane was assessed by determining the expression levels of osteogenic-related gene transcripts using quantitative real-time reverse-transcriptase polymerase chain reaction. Mineralization assay indicated that the p-rhOPN-C122 immobilized CMC/PEO-BC membrane promoted hPDLs osteogenic differentiation. These results suggested that the developed membrane could serve as a promising GTR membrane for application in bone tissue regeneration.

Zinc hybrid polyester barrier membrane accelerates guided tissue regeneration.

Barrier membranes play a pivotal role in the success of guided periodontal tissue regeneration. The biodegradable barriers predominantly used in clinical practice often lack sufficient barrier strength, antibacterial properties, and bioactivity, frequently leading to suboptimal regeneration outcomes. Although with advantages in mechanical strength, biodegradability and plasticity, bioinert aliphatic polyesters as barrier materials are usually polymerized via toxic catalysts, hard to be functionalized and lack of antibacterial properties. To address these challenges, we propose a new concept that controlled release of bioactive substance on the whole degradation course can give a bioinert aliphatic polyester bioactivity. Thus, a Zn-based catalytic system for polycondensation of dicarboxylic acids and diols is created to prepare zinc covalent hybrid polyester (PBS/ZnO). The atomically-dispersed Zn2+ ions entering main chain of polyester molecules endow PBS/ZnO barrier with antibacterial properties, barrier strength, excellent biocompatibility and histocompatibility. Further studies reveal that relying on long-term controlled release of Zn2+ ions, the PBS/ZnO membrane greatly expedites osteogenetic effect in guided tissue regeneration (GTR) by enhancing the mitochondrial function of macrophages to induce M2 polarization. These findings show a novel preparation strategy of bioactive polyester biomaterials based on long term controlled release of bioactive substance that integrates catalysis, material structures and function customization.

Remodeling of the Intra-Conduit Inflammatory Microenvironment to Improve Peripheral Nerve Regeneration with a Neuromechanical Matching Protein-Based Conduit.

Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra-conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory-polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein-based conduits. Moreover, the NGC can gradually regulate the intra-conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments.

Fabrication and characterization of a multi-functional GBR membrane of gelatin-chitosan for osteogenesis and angiogenesis.

Guided bone regeneration (GBR) membranes are widely used to treat bone defects. In this study, sequential electrospinning and electrospraying techniques were used to prepare a dual-layer GBR membrane composed of gelatin (Gel) and chitosan (CS) containing simvastatin (Sim)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (Sim@PLGA/Gel-CS). As a GBR membrane, Sim@PLGA/Gel-CS could act as a barrier to prevent soft tissue from occupying regions of bone tissue. Furthermore, compared with traditional GBR membranes, Sim@PLGA/Gel-CS played an active role on stimulating osteogenesis and angiogenesis. Determination of the physical, chemical, and biological properties of Sim@PLGA/Gel-CS membranes revealed uniform sizes of the nanofibers and microspheres and appropriate morphologies. Fourier-transform infrared spectroscopy was used to characterize the interactions between Sim@PLGA/Gel-CS molecules and the increase in the number of amide groups in crosslinked membranes. The thermal stability and tensile strength of the membranes increased after N-(3-dimethylaminopropyl)-N9- ethylcarbodiimide/N-hydroxysuccinimide crosslinking. The increased fiber density of the barrier layer decreased fibroblast migration compared with that in the osteogenic layer. Osteogenic function was indicated by the increased alkaline phosphatase activity, calcium deposition, and neovascularization. In conclusion, the multifunctional effects of Sim@PLGA/Gel-CS on the barrier and bone microenvironment were achieved via its dual-layer structure and simvastatin coating. Sim@PLGA/Gel-CS has potential applications in bone tissue regeneration.

Preparation and optimization of an eggshell membrane-based biomaterial for GTR applications.

OBJECTIVES: Guided Tissue Regeneration (GTR) is a popular clinical procedure for periodontal tissue regeneration. However, its key component, the barrier membrane, is largely collagen-based and is still quite expensive, posing a financial burden to the patients as well as healthcare systems and negatively impacting the patient's decision-making. Thus, our aim is to prepare a novel biomimetic GTR membrane utilizing a natural biomaterial, soluble eggshell membrane protein (SEP), which is economical as it comes from an abundant industrial waste from food and poultry industries, unlike collagen. Additive polymer, poly (lactic-co-glycolic acid) (PLGA), and a bioceramic, nano-hydroxyapatite (HAp), were added to improve its mechanical and biological properties. METHODS: For this barrier membrane preparation, we initially screened the significant factors affecting its mechanical properties using Taguchi orthogonal array design and further optimized the significant factors using response surface methodology. Furthermore, this membrane was characterized using SEM, EDAX, and ATR-FTIR, and tested for proliferation activity of human periodontal ligament fibroblasts (HPLFs). RESULTS: Optimization using response surface methodology predicted that the maximal tensile strength of 3.1 MPa and modulus of 39.9 MPa could be obtained at membrane composition of 8.9 wt% PLGA, 7.2 wt% of SEP, and 2 wt% HAp. Optimized PLGA/SEP/HAp membrane specimens that were electrospun on a static collector showed higher proliferation activity of HPLFs compared to tissue culture polystyrene and a commercial collagen membrane. SIGNIFICANCE: From the results observed, we can conclude that SEP-based nanofibrous GTR membrane could be a promising, environment-friendly, and cost-effective alternative for commercial collagen-based GTR membrane products.

Surface Modification of Nerve Guide Conduits with ECM Coatings and Investigating Their Impact on Schwann Cell Response.

In this study, layer-by-layer coatings composed of heparin and collagen are proposed as an extracellular mimetic environment on nerve guide conduits (NGC) to modulate the behavior of Schwann cells (hSCs). The authors evaluated the stability, degradation over time, and bioactivity of six bilayers of heparin/collagen layer-by-layer coatings, denoted as (HEP/COL)6. The stability study reveals that (HEP/COL)6 is stable after incubating the coatings in cell media for up to 21 days. The impact of (HEP/COL)6 on hSCs viability, protein expression, and migration is evaluated. These assays show that hSCs cultured in (HEP/COL)6 have enhanced protein expression and migration. This condition increases the expression of neurotrophic and immunomodulatory factors up to 1.5-fold compared to controls, and hSCs migrated 1.34 times faster than in the uncoated surfaces. Finally, (HEP/COL)6 is also applied to a commercial collagen-based NGC, NeuraGen, and hSC viability and adhesion are studied after 6 days of culture. The morphology of NeuraGen is not altered by the presence of (HEP/COL)6 and a nearly 170% increase of the cell viability is observed in the condition where NeuraGen is used with (HEP/COL)6. Additionally, cell adhesion on the coated samples is successfully demonstrated. This work demonstrates the reparative enhancing potential of extracellular mimetic coatings.

Advances in guided bone regeneration membranes: a comprehensive review of materials and techniques.

Guided tissue/bone regeneration (GTR/GBR) is a widely used technique in dentistry to facilitate the regeneration of damaged bone and tissue, which involves guiding materials that eventually degrade, allowing newly created tissue to take its place. This comprehensive review the evolution of biomaterials for guided bone regeneration that showcases a progressive shift from non-resorbable to highly biocompatible and bioactive materials, allowing for more effective and predictable bone regeneration. The evolution of biomaterials for guided bone regeneration GTR/GBR has marked a significant progression in regenerative dentistry and maxillofacial surgery. Biomaterials used in GBR have evolved over time to enhance biocompatibility, bioactivity, and efficacy in promoting bone growth and integration. This review also probes into several promising fabrication techniques like electrospinning and latest 3D printing fabrication techniques, which have shown potential in enhancing tissue and bone regeneration processes. Further, the challenges and future direction of GTR/GBR are explored and discussed.

Leveraging Oriented Lateral Walls of Nerve Guidance Conduit with Core-Shell MWCNTs Fibers for Peripheral Nerve Regeneration.

Peripheral nerve regeneration and functional recovery rely on the chemical, physical, and structural properties of nerve guidance conduits (NGCs). However, the limited support for long-distance nerve regeneration and axonal guidance has hindered the widespread use of NGCs. This study introduces a novel nerve guidance conduit with oriented lateral walls, incorporating multi-walled carbon nanotubes (MWCNTs) within core-shell fibers prepared in a single step using a modified electrohydrodynamic (EHD) printing technique to promote peripheral nerve regeneration. The structured conduit demonstrated exceptional stability, mechanical properties, and biocompatibility, significantly enhancing the functionality of NGCs. In vitro cell studies revealed that RSC96 cells adhered and proliferated effectively along the oriented fibers, demonstrating a favorable response to the distinctive architectures and properties. Subsequently, a rat sciatic nerve injury model demonstrated effective efficacy in promoting peripheral nerve regeneration and functional recovery. Tissue analysis and functional testing highlighted the significant impact of MWCNT concentration in enhancing peripheral nerve regeneration and confirming well-matured aligned axonal growth, muscle recovery, and higher densities of myelinated axons. These findings demonstrate the potential of oriented lateral architectures with coaxial MWCNT fibers as a promising approach to support long-distance regeneration and encourage directional nerve growth for peripheral nerve repair in clinical applications.

Soybean Oil-Based 3D Printed Mesh Designed for Guided Bone Regeneration (GBR) in Oral Surgery.

This study aims to obtain a cyto-compatible 3D printable bio-resin for the manufacturing of meshes designed from acquired real patients' bone defect to be used in future for guided bone regeneration (GBR), achieving the goal of personalized medicine, decreasing surgical, recovery time, and patient discomfort. To this purpose, a biobased, biocompatible, and photo-curable resin made of acrylated epoxidized soybean oil (AESO) diluted with soybean oil (SO) is developed and 3D printed using a commercial digital light processing (DLP) 3D printer. 3D printed samples show good thermal properties, allowing for thermally-based sterilization process and mechanical properties typical of crosslinked natural oils (i.e., E = 12 MPa, UTS = 1.5 MPa), suitable for the GBR application in the oral surgery. The AESO-SO bio-resin proves to be cytocompatible, allowing for fibroblast cells proliferation (viability at 72 h > 97%), without inducing severe inflammatory response when co-cultured with macrophages, as demonstrated by cytokine antibody arrays, that is anyway resolved in the first 24 h. Moreover, accelerated degradation tests prove that the bio-resin is biodegradable in hydrolytic environments.

Nerve Guide Conduits Integrated with Fisetin-Loaded Chitosan Hydrogels for Reducing Oxidative Stress, Inflammation, and Nerve Regeneration.

Peripheral nerve injuries (PNI) represent a prevalent and severe category of damage resulting from traumatic incidents. Predominantly, the deficiency in nerve regeneration can be ascribed to enduring inflammatory reactions, hence imposing substantial clinical implications for patients. Fisetin, a flavonoid derived from plants, is naturally present in an array of vegetables and fruits, including strawberries, apples, onions, and cucumbers. It exhibits immunomodulatory properties through the reduction of inflammation and oxidative stress. In the present research, a nerve defect is addressed for the first time utilizing a scaffold primed for controlled fisetin release. In this regard, fisetin-loaded chitosan hydrogels are incorporated into the lumen of polycaprolactone (PCL) nerve guide conduits (NGCs). The hydrogel maintained a steady release of an appropriate fisetin dosage. The study outcomes indicated that the fisetin/chitosan/polycaprolactone (FIS/CS/PCL) NGCs amplified Schwann cell proliferation and neural expression, curtailed oxidative stress, alleviated inflammation, and improved functions, electrophysiological properties, and morphology. This pioneering scaffold has the potential to contribute significantly to the field of neuroengineering.

Development of a PVA/PCL/CS-Based Nanofibrous Membrane for Guided Tissue Regeneration and Controlled Delivery of Doxycycline Hydrochloride in Management of Periodontitis: In Vivo Evaluation in Rats.

Antibiotic administration is an adjacent therapy to guided tissue regeneration (GTR) in the management of periodontitis. This is due to the major role of pathogen biofilm in aggravating periodontal defects. This study aimed to fabricate a GTR membrane for sustained delivery of doxycycline hydrochloride (DOX) while having a space-maintaining function. The membranes were prepared using a polymeric blend of polycaprolactone/polyvinyl alcohol/chitosan by the electrospinning technique. The obtained membranes were characterized in terms of physicochemical and biological properties. Nanofibers showed a mean diameter in the submicron range of < 450 nm while having uniform randomly aligned morphology. The obtained membranes showed high strength and flexibility. A prolonged in vitro release profile during 68 h was observed for manufactured formulations. The prepared membranes showed a cell viability of > 70% at different DOX concentrations. The formulations possessed antimicrobial efficacy against common pathogens responsible for periodontitis. In vivo evaluation also showed prolonged release of DOX for 14 days. The histopathological evaluation confirmed the biocompatibility of the GTR membrane. In conclusion, the developed nanofibrous DOX-loaded GTR membranes may have beneficial characteristics in favour of both sustained antibiotic delivery and periodontal regeneration by space-maintaining function without causing any irritation and tissue damage.

Healing outcomes of open versus closed flap procedures for collagen membrane coverage following immediate dental implant placements with simultaneous guided tissue regeneration.

OBJECTIVE: To compare the outcomes of open healing to complete closure for collagen membrane coverage for immediate implant placements with simultaneous guided bone regeneration (GBR) in two retrospective cohorts. METHODS: The subjects included 118 patients who received Bio-Gide® collagen membrane coverage for immediate implant placements and GBR in 20 anterior and 98 posterior teeth. For 58 patients, gingival flaps were released to achieve full coverage of collagen membrane (CC group). For 60 patients, no efforts were made to release the gingival flaps and collagen membrane was left exposed for open healing (OH group). Antibiotics and analgesics were prescribed for 7 days after surgery. The width of crestal open wounds were measured after surgery (W0), and at 1, 2 and 16 weeks (W16). Changes in bone mass were assessed by cone-beam computed tomography after implant placement and again at W16. Gingival and bone tissues over the implant cover screws were harvested and assessed for 16 patients in the OH group at W16. RESULTS: No wound dehiscence occurred in the CC group from W0 to W16. Both the vertical and horizontal bone dimension changes were not significantly different between the OH and CC group. For the OH group, soft tissue was completely healed at W16 when the initial wound widths were ≤6 mm. For those with initial wound widths ≥ 7 mm, the cover screws were exposed in 5/16 patients at W16 but did not affect the final restorations. Tissue staining showed keratinized mucosa and new bone formation above the dental implant in the OH group. CONCLUSION: Open healing achieved healing outcomes similar to those of complete closure for collagen membrane coverage following immediate implant placements. CLINICAL SIGNIFICANCE: For immediate implant placement requiring bone grafting and collagen membrane coverage, it is unnecessary to release the gingival flaps or use tissue grafts to achieve full coverage of the crestal wounds. Open healing with exposed membrane could achieve similar outcomes with less pain and swelling.

Perspectives on the Novel Multifunctional Nerve Guidance Conduits: From Specific Regenerative Procedures to Motor Function Rebuilding.

Peripheral nerve injury potentially destroys the quality of life by inducing functional movement disorders and sensory capacity loss, which results in severe disability and substantial psychological, social, and financial burdens. Autologous nerve grafting has been commonly used as treatment in the clinic; however, its rare donor availability limits its application. A series of artificial nerve guidance conduits (NGCs) with advanced architectures are also proposed to promote injured peripheral nerve regeneration, which is a complicated process from axon sprouting to targeted muscle reinnervation. Therefore, exploring the interactions between sophisticated NGC complexes and versatile cells during each process including axon sprouting, Schwann cell dedifferentiation, nerve myelination, and muscle reinnervation is necessary. This review highlights the contribution of functional NGCs and the influence of microscale biomaterial architecture on biological processes of nerve repair. Progressive NGCs with chemical molecule induction, heterogenous topographical morphology, electroactive, anisotropic assembly microstructure, and self-powered electroactive and magnetic-sensitive NGCs are also collected, and they are expected to be pioneering features in future multifunctional and effective NGCs.

A bi-layered asymmetric membrane loaded with demineralized dentin matrix for guided bone regeneration.

OBJECTIVES: Guided bone regeneration (GBR) is a well-established method for repairing hard tissue deficiency in reconstructive dentistry. The aim of this study was to investigate the barrier function, osteogenic activity and immunomodulatory ability of a novel bi-layered asymmetric membrane loaded with demineralized dentin matrix (DDM). METHODS: DDM particles were harvested from healthy, caries-free permanent teeth. Electrospinning technique was utilized to prepare bi-layered DDM-loaded poly(lactic-co-glycolic acid) (PLGA)/poly(lactic acid) (PLA) membranes (abbreviated as DPP bilayer membranes). We analyzed the membranes' surface properties, cytocompatibility and barrier function, and evaluated their osteogenic activity in vitro. In addition, its effects on the osteogenic immune microenvironment were also investigated. RESULTS: Synthetic DPP bilayer membranes presented suitable surface characteristics and satisfactory cytocompatibility. Transwell assays showed significant fewer migrated cells by the DPP bilayer membranes compared with blank control, with or without in vitro degradation (all P < 0.001). In vitro experiments indicated that our product elevated messenger ribonucleic acid (mRNA) expression levels of osteogenic genes alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN) and runt-related transcription factor 2 (Runx2). Among all groups, 20% DPP bilayer membrane displayed highest ALP activity (P < 0.001). Furthermore, DPP bilayer membranes enhanced the mRNA expression of M2 macrophage markers and increased the proportion of CD206+ M2 macrophages by 100% (20% DPP: P < 0.001; 30% DPP: P < 0.001; 40% DPP: P < 0.05), thus exerting an inflammation suppressive effect. CONCLUSIONS: DPP bilayer membranes exhibited notable biological safety and osteogenic activity in vitro, and have potential as a prospective candidate for GBR approach in the future.

Electrospun Nanofibrous Conduit Filled with a Collagen-Based Matrix (ColM) for Nerve Regeneration.

Traumatic nerve defects result in dysfunctions of sensory and motor nerves and are usually accompanied by pain. Nerve guidance conduits (NGCs) are widely applied to bridge large-gap nerve defects. However, few NGCs can truly replace autologous nerve grafts to achieve comprehensive neural regeneration and function recovery. Herein, a three-dimensional (3D) sponge-filled nanofibrous NGC (sf@NGC) resembling the structure of native peripheral nerves was developed. The conduit was fabricated by electrospinning a poly(L-lactide-co-glycolide) (PLGA) membrane, whereas the intraluminal filler was obtained by freeze-drying a collagen-based matrix (ColM) resembling the extracellular matrix. The effects of the electrospinning process and of the composition of ColM on the physicochemical performance of sf@NGC were investigated in detail. Furthermore, the biocompatibility of the PLGA sheath and ColM were evaluated. The continuous and homogeneous PLGA nanofiber membrane had high porosity and tensile strength. ColM was shown to exhibit an ECM-like architecture characterized by a multistage pore structure and a high porosity level of over 70%. The PLGA sheath and ColM were shown to possess stagewise degradability and good biocompatibility. In conclusion, sf@NGC may have a favorable potential for the treatment of nerve reconstruction.