Double-layered Scaffold Research Articles

3D printing of flexible piezoelectric composite with integrated sensing and actuation applications

3D printing of flexible piezoelectric composites (3D-FPCs) is increasingly attracting the attention due to its unique advantage for customized smart applications. However, current research mainly focuses on the 0–3 piezoelectric composites, in which the piezoelectric ceramics are embedded in polymer matrix in the form of particles. The poor connectivity between particles much reduces the conduction of strain and charge in the composites, seriously limiting its application in actuation. In this work, a continuous lead zirconate titanate (PZT) double-layer ceramic scaffold was prepared by 3D printing and assembled with epoxy resin and interdigital electrodes together to manufacture a multifunctional device. The 3D-FPCs exhibit a free strain of 1830 ​ppm in actuating and are able to actuate a stainless-steel cantilever beam to produce a tip displacement of 5.71 ​mm. Additionally, the devices exhibit a sensitivity of 26.81V/g in sensing applications. Furthermore, 3D-FPCs are demonstrated as actuators for mobile small robots and wearable sensors for sensing joint activities.

Integrating coaxial electrospinning and 3D printing technologies for the development of biphasic porous scaffolds enabling spatiotemporal control in tumor ablation and osteochondral regeneration

The osteochondral defects (OCDs) resulting from the treatment of giant cell tumors of bone (GCTB) often present two challenges for clinicians: tumor residue leading to local recurrence and non-healing of OCDs. Therefore, this study focuses on developing a double-layer PGPC-PGPH scaffold using shell-core structure nanofibers to achieve “spatiotemporal control” for treating OCDs caused by GCTB. It addresses two key challenges: eliminating tumor residue after local excision and stimulating osteochondral regeneration in non-healing OCD cases. With a shell layer of protoporphyrin IX (PpIX)/gelatin (GT) and inner cores containing chondroitin sulfate (CS)/poly(lactic-co-glycolic acid) (PLGA) or hydroxyapatite (HA)/PLGA, coaxial electrospinning technology was used to create shell-core structured PpIX/GT-CS/PLGA and PpIX/GT-HA/PLGA nanofibers. These nanofibers were shattered into nano-scaled short fibers, and then combined with polyethylene oxide and hyaluronan to formulate distinct 3D printing inks. The upper layer consists of PpIX/GT-CS/PLGA ink, and the lower layer is made from PpIX/GT-HA/PLGA ink, allowing for the creation of a double-layer PGPC-PGPH scaffold using 3D printing technique. After GCTB lesion removal, the PGPC-PGPH scaffold is surgically implanted into the OCDs. The sonosensitizer PpIX in the shell layer undergoes sonodynamic therapy to selectively damage GCTB tissue, effectively eradicating residual tumors. Subsequently, the thermal effect of sonodynamic therapy accelerates the shell degradation and release of CS and HA within the core layer, promoting stem cell differentiation into cartilage and bone tissues at the OCD site in the correct anatomical position. This innovative scaffold provides temporal control for anti-tumor treatment followed by tissue repair and spatial control for precise osteochondral regeneration.

In vitro assessment of Momordica charantia/Hypericum perforatum oils loaded PCL/Collagen fibers: Novel scaffold for tissue engineering.

The research on tissue engineering applications has been progressing to manufacture ideal tissue scaffold biomaterials. In this study, a double-layered electrospun biofiber scaffold biomaterial including Polycaprolactone (PCL)/Collagen (COL) fibrous inner layer and PCL/ Momordica charantia (MC) and Hypericum perforatum (HP) oils fibrous outer layer was developed to manufacture a functional, novel tissue scaffold with the advantageous mechanical and biological properties. The main approach was to combine the natural perspective using medicinal oils with an engineering point of view to fabricate a potential functional scaffold for tissue engineering. Medicinal plants MC and HP are rich in functional oils and incorporation of them in a tissue scaffold will unveil their potential to augment both new tissue formation and wound healing. In this study, a novel double-layered scaffold prototype was fabricated using electrospinning technique with two PCL fiber layers, first is composed of collagen, and second is composed of oils extracted from medicinal plants. Initially, the composition of plant oils was analyzed. Thereafter the biofiber scaffold layers were fabricated and were evaluated in terms of morphology, physicochemistry, thermal and mechanical features, wettability, in vitro bio-degradability. Double-layered scaffold prototype was further analyzed in terms of in vitro biocompatibility and antibacterial effect. The medicinal oils blend provided antioxidant and antibacterial properties to the novel PCL/Oils layer. The results signify that inner PCL/COL layer exhibited advanced biodegradability of 8.5% compared to PCL and enhanced wettability with 11.7° contact angle. Strength of scaffold prototype was 5.98 N/mm2 thanks to the elastic PCL fibrous matrix. The double-layered functional biofiber scaffold enabled 92% viability after 72 h contact with fibroblast cells and furthermore provided feasible attachment sites for the cells. The functional scaffold prototype's noteworthy mechanical, chemical, and biological features enable it to be suggested as a different novel biomaterial with the potential to be utilized in tissue engineering applications.

Poly(l-lactic acid)-based double-layer composite scaffold for bone tissue repair.

Bone defect is a serious threat to human health. Osteopractic total flavone (OTF) extracted from Rhizoma Drynariae has the effects of promoting bone formation. Panax notoginseng saponin (PNS) has the function of activating blood circulation and removing blood stasis. Therefore, combining OTF and PNS with poly(l-lactic acid) (PLLA) to prepare scaffolds containing PNS in the outer layer and OTF in the inner layer is a feasible solution to rapidly remove blood stasis and continue to promote bone formation. In addition, degradation rate of the scaffold can affect the release time of two drugs. Adding Mg particles in outer layer can control the degradation rate of the scaffold and the drug release. Therefore, a double-layer drug-loaded PLLA scaffold containing OTF in the inner layer, PNS and Mg particles in the outer layer was prepared and characterized to verify its feasibility. The experimental results showed that the scaffold can realize the rapid release of PNS and the continuous release of OTF. With the increase of Mg content, the drug release rate became faster. Animal experiments showed that the scaffold containing 5% Mg particles could effectively promote the formation of new bone in the bone defect of male New Zealand white rabbits, and the area and density of new bone formed were much better than those in the control group. These results demonstrated that the double-layer drug-loaded scaffold had good ability to promote bone repair.

Adipose-Derived Stromal Cells Preserve Pancreatic Islet Function in a Transplantable 3D Bioprinted Scaffold.

Intra-portal islet transplantation is currently the only clinically approved beta cell replacement therapy, but its outcome is hindered by limited cell survival due to a multifactorial reaction against the allogeneic tissue in liver. Adipose-derived stromal cells (ASCs) can potentially improve the islet micro-environment by their immunomodulatory action. The challenge is to combine both islets and ASCs in a relatively easy and consistent long-term manner in a deliverable scaffold. Manufacturing the 3D bioprinted double-layered scaffolds with primary islets and ASCs using a mix of alginate/nanofibrillated cellulose (NFC) bioink is reported. The diffusion properties of the bioink and the supportive effect of human ASCs on islet viability, glucose sensing, insulin secretion, and reducing the secretion of pro-inflammatory cytokines are demonstrated. Diabetic mice transplanted with islet-ASC scaffolds reach normoglycemia seven days post-transplantation with no significant difference between this group and the group received islets under the kidney capsules. In addition, animals transplanted with islet-ASC scaffolds stay normoglycemic and show elevated levels of C-peptide compared to mice transplanted with islet-only scaffolds. The data present a functional 3D bioprinted scaffold for islets and ASCs transplanted to the extrahepatic site and suggest a possible role of ASCs on improving the islet micro-environment.

Lineage-specific multifunctional double-layer scaffold accelerates the integrated regeneration of cartilage and subchondral bone

Repairing cartilage/subchondral bone defects that involve subchondral bone is a major challenge in clinical practice. Overall, the integrated repair of the structure and function of the osteochondral (OC) unit is very important. Some studies have demonstrated that the differentiation of cartilage is significantly enhanced by reducing the intake of nutrients such as lipids. This study demonstrates that using starvation can effectively optimize the therapeutic effect of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs). A hyaluronic acid (HA)-based hydrogel containing starved BMSCs-EVs displayed continuous release for more than 3 weeks and significantly promoted the proliferation and biosynthesis of chondrocytes around the defect regulated by the forkhead-box class O (FOXO) pathway. When combined with vascular inhibitors, the hydrogel inhibited cartilage hypertrophy and facilitated the regeneration of hyaline cartilage. A porous methacrylate gelatine (GelMA)-based hydrogel containing calcium salt loaded with thrombin rapidly promoted haematoma formation upon contact with the bone marrow cavity to quickly block the pores and prevent the blood vessels in the bone marrow cavity from invading the cartilage layer. Furthermore, the haematoma could be used as nutrients to accelerate bone survival. The in vivo experiments demonstrated that the multifunctional lineage-specific hydrogel promoted the integrated regeneration of cartilage/subchondral bone. Thus, this hydrogel may represent a new strategy for osteochondral regeneration and repair.

Preliminary studies on intimal injury related to stent retrieval in a canine model

ObjectiveThis pilot study aimed to observe intimal injuries related to stent retrieval in the iliac artery of a canine. BackgroundIn-stent restenosis remains challenging owing to permanent stent implantation. A retrievable stent may be alternative for intervention without permanent residue. MethodsFive retrievable stents with point-to-point overlapped double-layer scaffolds were deployed into the iliac arteries and retrieved on days 14, 21, 28, 35, and 42 from five canines. ResultsArterial diameter decreased by 9–10% before retrieval and 15% on day 14 after retrieval. In the 14-day-stent, the stent surface was clean without visible fibrin. In the 28-day-stent, the overlay was mainly composed of fibrin and fibroblasts. The proliferation of smooth muscle cells has not yet been observed with α-smooth muscle actin staining. In the 42-day-stent, endothelial and smooth muscle cells decreased under the struts, and the internal elastic lamina was interrupted segmentally. Neointima formation involves fibroblasts and smooth muscle cells. Neointimal thickness was negatively correlated with strut space. Stent traces on the artery wall tended to be flat at a follow-up14 days after retrieval. The primary intima was completely covered by neointima. Two stents could not be retrieved because of in-stent thrombosis or capture loss. ConclusionsThe stent was covered mainly by depositional fibrin after 28 days and by typical neointima after 42 days. The stent retrieval procedure did not induce injury to vascular smooth muscle, and the intima repair was performed 14 days after stent retrieval.

Assessment of Esophageal Reconstruction via Bioreactor Cultivation of a Synthetic Scaffold in a Canine Model.

Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals that requires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment of peristalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaffold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model. We fabricated a novel double-layered scaffold as a tissue-engineered esophagus using an electrospinning technique. Prior to transplantation, human-derived mesenchymal stem cells were seeded into the lumen of the scaffold, and bioreactor cultivation was performed to enhance cellular reactivity. After 3 days of cultivation using the bioreactor system, tissue-engineered artificial esophagus was transplanted into a partial esophageal defect (5×3 cm-long resection) in a canine model. Scanning electron microscopy (SEM) showed that the electrospun fibers in a tubular scaffold were randomly and circumferentially located toward the inner and outer surfaces. Complete recovery of the esophageal mucosa was confirmed by endoscopic analysis and SEM. Esophagogastroduodenoscopy and computed tomography also showed that there were no signs of leakage or stricture and that there was a normal lumen with complete epithelialization. Significant regeneration of the mucosal layer was observed by keratin-5 immunostaining. Alpha-smooth muscle actin immunostaining showed significantly greater esophageal muscle regeneration at 12 months than at 6 months. Custom-designed bioreactor cultured electrospun polyurethane scaffolds can be a promising approach for esophageal tissue engineering.

In situ fabrication of an anisotropic double-layer hydrogel as a bio-scaffold for repairing articular cartilage and subchondral bone injuries.

Articular cartilage is a smooth and elastic connective tissue playing load-bearing and lubricating roles in the human body. Normal articular cartilage comprises no blood vessels, lymphatic vessels, nerves, or undifferentiated cells, so damage self-repair is very unlikely. The injuries of articular cartilage are often accompanied by damage to the subchondral bone. The subchondral bone mainly provides mechanical support for the joint, and the successful repair of articular cartilage depends on the ability of the subchondral bone to provide a suitable environment. Currently, conventional repair treatments for articular cartilage and subchondral bone defects can hardly achieve good results due to the poor self-repairing ability of the cartilage Here, we propose a bioactive injectable double-layer hydrogel to repair articular cartilage and subchondral bone. The hydrogel scaffold mimics the multilayer structure of articular cartilage and subchondral bone. Agarose was used as a common base material for the double-layer hydrogel scaffold, in which a sodium alginate (SA)/agarose layer was used for the repair of artificially produced subchondral bone defects, while a decellularized extracellular matrix (dECM)/agarose layer was used for the repair of articular cartilage defects. The double-layer hydrogel scaffold is injectable, easy to use, and can fill in the damaged area. The hydrogel scaffold is also anisotropic both chemically and structurally. Animal experiments showed that the surface of the new cartilage tissue in the double-layer hydrogel scaffold group was closest to normal articular cartilage, with a structure similar to that of hyaline cartilage and a preliminary calcified layer. Moreover, the new subchondral bone in this group exhibited many regular bone trabeculae, and the new cartilage and subchondral bone were mechanically bound without mutual intrusion and tightly integrated with the surrounding tissue. The continuous double-layer hydrogel scaffold prepared in this study mimics the multilayer structure of articular cartilage and subchondral bone and promotes the functional repair of articular cartilage and subchondral bone, favoring close integration between the newborn tissue and the original tissue.

A novel in vitro blood-brain barrier model using 3D bioprinter: A pilot study

3D bioprinters allow the creation of functional tissues using various cell lines. The blood-brain barrier (BBB) is crucial for maintaining homeostasis in the brain, acting as a protective interface between the cerebral blood vessels and the brain parenchyma. Advancements in tissue engineering have led to the development of in vitro BBB models. However, model accuracy and reproducibility still require improvements. Thus, we hypothesized that producing BBB models using a 3D bioprinter is a novel method to overcome these limitations. We tested the maintainability of habitable conditions for cells and the durability of the 3D-bioprinted BBB model. We printed four different BBB models using a bio-ink composed of Matrigel base and CPA47 endothelial cells: single- and double-layered square and circular scaffolds. The double-layered square scaffold fostered optimal BBB functions as it most effectively maintained a fixed shape and initial cell positions. When A172 glioblastoma cells were placed in the empty square spaces of the square BBB scaffold, most cells were alive and healthy after 96 hours. Although A172 cells remained in their initial cell positions until the first 48 hours, we observed movement across the Matrigel barrier when checked at 96 hours. At 48 hours, A172 cells showed no movement from their initial positions; however, by 96 hours, we observed clear movement of A172 cells across the Matrigel barrier. Due to its relative cost-effectiveness and high reproducibility, our BBB model has several applications, especially for studying brain cancer metastasis past the BBB and developing potential corresponding clinical therapeutics.

Biomimetic hybrid scaffold containing niosomal deferoxamine promotes angiogenesis in full-thickness wounds

Effective management of full-thickness wounds faces significant challenges due to poor angiogenesis and impaired healing. Biomimetic tissue-engineered scaffolds with angiogenic properties can, however, enhance the regeneration capacity of the damaged skin. Here, we developed a hybrid double-layer nanofibrous scaffold, comprised of egg white (EW) and polyvinyl alcohol (PVA), loaded with niosomal Deferoxamine (NDFO) for enhanced angiogenesis and wound healing features. The hybrid scaffold showed enhanced mechanical properties with comparable modulus and shape-recovery behavior of the human skin. Thanks to the porous morphology and uniform distribution of NDFO within the nanofibers, in vitro drug release studies indicated controlled and sustained release of DFO for up to 9 days. The constructs also promoted a significant increase in vascular sprouting area in vitro and enhanced vascular branches ex vivo. In vivo, implantation of the hybrid scaffold in full-thickness wounds in rats revealed early angiogenic response, a higher number of neo-formed vessels, a faster healing rate and complete epithelialization as early as day 10, compared to the control groups. Thus, the presented biomimetic hybrid scaffold with DFO control release features holds great promise in accelerated full-thickness wound healing and soft tissue regeneration.

Freeze-casting osteochondral scaffolds: The presence of a nutrient-permeable film between the bone and cartilage defect reduces cartilage regeneration

Microfracture treatment that is basically relied on stem cells and growth factors in bone marrow has achieved a certain progress for cartilage repair in clinic. Nevertheless, the neocartilage generated from the microfracture strategy is limited endogenous regeneration and prone to fibrosis due to the influences of cell inflammation and vascular infiltration. To explore the crucial factor for articular cartilage remodeling, here we design a trilaminar osteochondral scaffold with a selective permeable film in middle isolation layer which can prevent stem cells, immune cells, and blood vessels in the bone marrow from invading into the cartilage layer, but allow the nutrients and cytokines to penetrate. Our findings show that the trilaminar scaffold exhibits a good biocompatibility and inflammatory regulation, but the osteochondral repair is far less effective than the control of double-layer scaffold without isolation layer. These results demonstrate that it is not adequate to rely only on nutrients and cytokines to promote reconstruction of articular cartilage, and the various cells in bone marrow are indispensable. Consequently, the current study illustrates that cell infiltration involving stem cells, immune cells and other cells from bone marrow plays a crucial role in articular cartilage remodeling based on the integrated scaffold strategy. Statement of significanceClinical microfracture treatment plays a certain role on the restoration of injured cartilage, but the regenerative cartilage is prone to be fibrocartilage due to the modulation of bone marrow cells. Herein, we design a trilaminar osteochondral scaffold with a selective permeable film in middle isolation layer. This specific film made of dense electrospun nanofiber can prevent bone marrow cells from invading into the cartilage layer, but allow the nutrients and cytokines to penetrate. Our conclusion is that the cartilage remodeling will be extremely inhibited when the bone marrow cells are blocking. Owing to the diverse cells in bone marrow, we will further explore the influence of each cell type on cartilage repair in our continuous future work.

A bionic composite hydrogel with dual regulatory functions for the osteochondral repair

Due to the avascular nature of cartilage, it is difficult to heal and regenerate spontaneously after injury. At present, tissue engineering has become a promising strategy for repairing damaged cartilage, but the use of seed cells and growth factors is limited. In addition, the importance of mechanical compatibility of scaffold materials is often ignored. In this study, osteochondral scaffold was designed as a bilayer structure with a dense γ-Polyglutamic acid/carboxymethyl chitosan/bacterial cellulose (PGA/CMCS/BC) hydrogel cartilage layer and a porous nano HA-containing PGA/CMCS/BC hydrogel osteogenic layer. In addition, bioactive ions were introduced into the hydrogel scaffold to adjust the mechanical and swelling properties of the material to match the mechanical properties of natural articular cartilage. At the same time, based on the structural characteristics of bone and cartilage, magnesium and copper ions were introduced into the double-layer hydrogel scaffold, respectively, to prepare the cartilage layer and the bone layer, which endowed the material with excellent antibacterial properties and achieved the purpose of the integrated repair of bone and cartilage. The results showed that, after adding magnesium ions, the tensile breaking strength of material was increased from 0.66 MPa to 1.37 MPa，the corresponding compression modulus of the material (strain 0–12%) increased from 0.15 MPa to 0.58 MPa whilst the maximum mass swelling rate decreased from 155% to 75%. The results of in vivo experiments show that the group with bioactive ions had a much better effect on the repair of osteochondral defects, compared with group without bioactive ions, demonstrating such double ion regulation strategy is a very practical strategy for the treatment of osteochondral defects.

Preparation of SF/SF-nHA double-layer scaffolds for periodental tissue regeneration

Silk fibroin (SF) film/porous SF-nanohydroxyapatite (nHA) double-layer composite scaffolds were fabricated by a combination of electrospinning, casting and freeze-drying. The results showed that the tensile strength and elongation of the SF film layer were significantly improved through the bridging effect of SF/(ε-caprolactone) fibers in the SF matrix. The pore size in SF-nHA porous scaffold layer was approximately 213 μm, and nHA enhanced the compressive strength of the scaffold. CCK-8 assay showed that the SF/SF-nHA scaffold not only had no obvious cytotoxicity but also significantly promoted cell proliferation. The scaffold has the potential to be used for periodontal tissue regeneration.

Repair of osteochondral defects mediated by double-layer scaffolds with natural osteochondral-biomimetic microenvironment and interface.

Tissue engineering provides a new approach for the treatment of osteochondral defects. However, the lack of an ideal double-layer scaffold with osteochondral-biomimetic microenvironment and interface similar to native articular tissue greatly limits clinical translation. Our current study developed a double-layer acellular osteochondral matrix (AOM) scaffold with natural osteochondral-biomimetic microenvironment and interface by integrating ultraviolet (UV) laser and decellularization techniques. The laser parameters were optimized to achieve a proper pore depth close to the osteochondral interface, which guaranteed complete decellularization, sufficient space for cell loading, and relative independence of the chondrogenic and osteogenic microenvironments. Gelatin-methacryloyl (GelMA) hydrogel was further used as the cell carrier to significantly enhance the efficiency and homogeneity of cell loading in the AOM scaffold with large pore structure. Additionally, in vitro results demonstrated that the components of the AOM scaffold could efficiently regulate the chondrogenic/osteogenic differentiations of bone marrow stromal cells (BMSCs) by activating the chondrogenic/osteogenic related pathways. Importantly, the AOM scaffolds combined with BMSC-laden GelMA hydrogel successfully realized tissue-specific repair of the osteochondral defects in a knee joint model of rabbit. The current study developed a novel double-layer osteochondral biomimetic scaffold and feasible strategy, providing strong support for the tissue-specific repair of osteochondral defects and its future clinical translation.

Preliminary Results on Heparin-Modified Double-Layered PCL and PLA-Based Scaffolds for Tissue Engineering of Small Blood Vessels.

Low-diameter blood vessels are challenging to replace with more traditional synthetic vascular grafts. Therefore, the obvious choice is to try to regenerate small veins and arteries through tissue-engineering approaches. However, the layered structure of native vessels and blood compatibility issues make this a very challenging task. The aim of this study is to create double-layered tubular scaffolds with enhanced anticoagulant properties for the tissue engineering of small blood vessels. The scaffolds were made of a polycaprolactone-based porous outer layer and a polylactide-based electrospun inner layer modified with heparin. The combination of thermally induced phase separation and electrospinning resulted in asymmetric scaffolds with improved mechanical properties. The release assay confirmed that heparin is released from the scaffolds. Additionally, anticoagulant activity was shown through APTT (activated partial thromboplastin time) assay. Interestingly, the endothelial cell culture test revealed that after 14 days of culture, HAECs (human aortic endothelial cell lines) tended to organize in chain-like structures, typical for early stages of vascular formation. In the longer culture, HAEC viability was higher for the heparin-modified scaffolds. The proposed scaffold design and composition have great potential for application in tissue engineering of small blood vessels.

Double-layered and shape-stabilized phase change materials with enhanced thermal conduction and reversible thermochromism for solar thermoelectric power generation

Energy conversion technologies and systems associated with phase change materials (PCMs) have gained great popularity recently. How to convert the heat captured from solar energy into applicable electricity is significant and challenging, in particular for stable power output. Given that three-dimensional (3D) structural scaffold can ameliorate shape stability and thermal conductivity simultaneously, a novel double-layered multifunctional 3D hybrid scaffold is developed through two-step freeze-casting to produce leakage-proof photodriven composite PCMs with enhanced thermal conductivity for efficient light-thermoelectric conversion. The as-prepared double-layered scaffold is composed of black bacterial cellulose (BC)/thermochromic particle (TP) upper layer with the function of reversible photoabsorption and white BC/boron nitride (BN) lower layer with the function of heat conduction. The resultant leakage-proof composite PCMs exhibit high thermal conductivity up to 3.26 W/(mK) at a BN loading of 16.3 vol% and improved reversible photoabsorption ability. When used as heat source in a light-thermoelectric power generation system, a long-term stable output voltage of 287 mV is generated, achieving effective conversion from renewable solar energy to applicable electricity.

Bilayered scaffold with 3D printed stiff subchondral bony compartment to provide constant mechanical support for long-term cartilage regeneration.

Background/ObjectiveWe seek to figure out the effect of stable and powerful mechanical microenvironment provided by Ti alloy as a part of subchondral bone scaffold on long-term cartilage regeneration.Methods: we developed a bilayered osteochondral scaffold based on the assumption that a stiff subchondral bony compartment would provide stable mechanical support for cartilage regeneration and enhance subchondral bone regeneration. The subchondral bony compartment was prepared from 3D printed Ti alloy, and the cartilage compartment was created from a freeze-dried collagen sponge, which was reinforced by poly-lactic-co-glycolic acid (PLGA).ResultsIn vitro evaluations confirmed the biocompatibility of the scaffold materials, while in vivo evaluations demonstrated that the mechanical support provided by 3D printed Ti alloy layer plays an important role in the long-term regeneration of cartilage by accelerating osteochondral formation and its integration with the adjacent host tissue in osteochondral defect model at rabbit femoral trochlea after 24 weeks.ConclusionMechanical support provided by 3D printing Ti alloy promotes cartilage regeneration by promoting subchondral bone regeneration and providing mechanical support platform for cartilage synergistically.Translational potential statementThe raw materials used in our double-layer osteochondral scaffolds are all FDA approved materials for clinical use. 3D printed titanium alloy scaffolds can promote bone regeneration and provide mechanical support for cartilage regeneration, which is very suitable for clinical scenes of osteochondral defects. In fact, we are conducting clinical trials based on our scaffolds. We believe that in the near future, the scaffold we designed and developed can be formally applied in clinical practice.

Exosomes from 3T3-J2 promote expansion of tracheal basal cells to facilitate rapid epithelization of 3D-printed double-layer tissue engineered trachea

Functional epithelization plays a pivotal role in maintaining long-term lumen patency of tissue-engineered trachea (TET). Due to the slow migration of autologous epithelium, spontaneous epithelization process of transplanted TET is always tardive. Seeding tracheal basal cells (TBCs) on TET before transplantation might be favorable for accelerating epithelization, but rapid expansion of TBCs in vitro is still relatively intractable. In this study, we proposed a promising expansion strategy which enables the TBCs to proliferate rapidly in vitro. TBCs were isolated from the autologous tracheal mucosae of rabbit, and co-cultured with exosomes derived from 3T3-J2 cells. After co-culture with exosomal component, TBCs could vigorously proliferate in vitro and retained their multi-potency. It was in stark contrast to that the single-cultured TBCs could only be expand to passage 2 in about 30 days, moreover, the most majority of single-cultured cells entered late apoptotic stage. On the other hand, a bionic tubular double-layer scaffold with good mechanical property and bio-compatibility was designed and fabricated by 3D printing technology. Then TET with bi-lineage cell-type was constructed in vitro by implanting autologous chondrocytes on the outer-layer of scaffold, and TBCs on the inner-layer, respectively. And then TET was pre-vascularized in vivo, and pedicled transplanted to restore long-segmental defect in recipient rabbits. It was found that the chondrocytes and TBCs seeded on double-layer scaffolds developed well as expected. And almost complete coverage with ciliated epitheliums was observed on the lumen surface of TET 2-week after operation, in comparison with that the epithelization of TET without pre-seeding of TBCs accomplished nearly 2-month after operation. In conclusion, the promising expansion strategy of TBCs together with 3D-printed double-layer scaffolds facilitate the rapid epithelization process of transplanted TET, which might be of vital significance for clinical and translational medicine.

Effects of PbS quantum dots layer and different light scattering films on the photovoltaic performance of double passivated PbS, CdS and CdSe quantum dots sensitized solar cells

In this research, two novel multi-layer photoelectrodes were fabricated and applied in quantum dot sensitized solar cells (QDSCs). The double layer scaffolds were composed of a TiO2 nanocrystalline sub-layer covered with an over-grown TiO2 nanorods (NRs) or ex-synthesized TiO2 hollow spheres (HSs) film. The light sensitization was carried out by deposition of separated PbS, CdS and CdSe quantum dots (QDs) layers. Finally, two electron blocking/passivating films of ZnS and SiO2 were formed for better photovoltaic (PV) performance. The syntheses of TiO2 nanocrystals (NCs), HSs and NRs were performed and tuned through different hydrothermal methods. The depositions of the PbS, CdS and ZnS layers were carried out by conventional successive ionic layer adsorption and reaction (SILAR) process. The CdSe and SiO2 films were also formed using a modified, effective chemical bath deposition (CBD) and sol–gel techniques, respectively. The PbS sensitizing film was additionally utilized for higher PV efficiency and the number of deposition cycles(X) was altered for the purpose of optimization. For the cell with novel TiO2NCs/TiO2NRs/PbS(X)/CdS/CdSe/ZnS/SiO2, X = 0–3, photoanode, the highest efficiency was about 5.5% and achieved for X = 2. This power conversion efficiency (PCE) was enhanced about 28% compared to that of the PbS free photoelectrode. The other improved TiO2 NCs/TiO2HSs/PbS(X)/CdS/CdSe/ZnS/SiO2, X = 0–3, photoanode was also utilized with a light scattering HSs film. The maximum efficiency was achieved about 6.5% for the extra PbS(2) sensitizing layer. This PCE was increased about 20% compared to the PbS free photoelectrode and 51% compared to that of the QDSC with the PbS free, NRs included photoanode. The highest efficiency was attributed to the co-sensitization and optimized PbS sensitizing layer together with the effective light scattering and utilization of double passivating layers.