The Making of a Flight Feather: Bio-architectural Principles and Adaptation.

The evolution of flight in feathered dinosaurs and early birds over millions of years required flight feathers whose architecture features hierarchical branches. While barb-based feather forms were investigated, feather shafts and vanes are understudied. Here, we take a multi-disciplinary approach to study their molecular control and bio-architectural organizations. In rachidial ridges, epidermal progenitors generate cortex and medullary keratinocytes, guided by Bmp and transforming growth factor ß (TGF-ß) signaling that convert rachides into adaptable bilayer composite beams. In barb ridges, epidermal progenitors generate cylindrical, plate-, or hooklet-shaped barbule cells that form fluffy branches or pennaceous vanes, mediated by asymmetric cell junction and keratin expression. Transcriptome analyses and functional studies show anterior-posterior Wnt2b signaling within the dermal papilla controls barbule cell fates with spatiotemporal collinearity. Quantitative bio-physical analyses of feathers from birds with different flight characteristics and feathers in Burmese amber reveal how multi-dimensional functionality can be achieved and may inspire future composite material designs. VIDEO ABSTRACT.

Posterior-Stabilized Antibiotic Cement Articulating Spacer With Endoskeleton-Reinforced Cam Reduces Rate of Post-Cam Mechanical Complications in Prosthetic Knee Infection: A Preliminary Study.

BACKGROUND: Posterior-stabilized antibiotic cement articulating spacers (PS spacers) reduce spacer mechanical complications in prosthetic knee infections (PKIs); however, joint dislocation after femoral cam fracture has been reported. We hypothesized that the rate of post-cam mechanical complications is lower in PS spacers with an endoskeleton-reinforced cam. METHOD: A retrospective study of PKIs using PS spacers with or without a Kirschner wire-reinforced cam (K-PS or nK-PS spacers, respectively) was conducted between 2015 and 2019. The rates of post-cam mechanical complications and reoperation, as well as risk factors for post or cam failure, were analyzed. RESULTS: The cohort included 118 nK-PS and 49 K-PS spacers. All patients were followed up for 2 years. The rate of joint subluxation/dislocation after femoral cam fracture was lower in K-PS (0%) than in nK-PS spacers (17.8%; P = .002). The reoperation rate for spacer mechanical complications was lower in K-PS (0%) than in nK-PS spacers (11.9%; P = .008). The identified risk factors for femoral cam fractures were body mass index ≥25 kg/m2, femoral spacer size ≤2, and surgical volume ≤12 resection arthroplasties per year. CONCLUSION: This preliminary study highlights that K-PS spacers have a lower rate of post-cam mechanical complications than nK-PS spacers. We recommend the use of PS spacers with endoskeleton-reinforced cam when treating PKIs performed by surgeons with lower surgical volumes, especially in patients with higher body mass index and smaller femoral spacer sizes.

Cruciate-Retaining vs Posterior-Stabilized Antibiotic Cement Articulating Spacers for Two-Stage Revision of Prosthetic Knee Infection: A Retrospective Cohort Study.

BACKGROUND: Antibiotic cement articulating spacers are recommended during 2-stage revision for prosthetic knee infection because of increased range of motion (ROM) and improved function; however, spacer mechanical complications have been reported. We aimed to determine the association between different constraints of articulating spacers and the rate of complications and infection eradication, functional outcomes, and ROM. METHODS: A retrospective study of prosthetic knee infection using cruciate-retaining (CR) or posterior-stabilized (PS) spacers was conducted between 2011 and 2018. The rate of spacer mechanical complications, infection eradication after reimplantation and reoperation, Hospital of Special Surgery (HSS) knee score, and ROM during the interim stage were analyzed. All patients were regularly followed up for 2 years. RESULTS: One hundred forty-one patients were included, with 66 CR and 75 PS spacers. Overall mechanical complication rate was lower in PS (9.3%) than in CR spacers (45.5%) (P < .001), especially in joint dislocation (1.3% vs 30.3%, respectively, P < .001). Overall reoperation rate was lower in PS (16.0%) than in CR spacers (36.4%) (P < .001), especially for mechanical complications (1.3% vs 24.2%, respectively, P < .001). HSS knee score was higher in PS (72.3) than in CR spacers (63.8) (P < .001). ROM was greater in PS (90.3°) than in CR spacers (80.6°) (P = .005), especially at maximum flexion (102.4° vs 89.6°, respectively, P = .003). Infection eradication was comparable between the spacers. CONCLUSION: Both spacers can control infection; however, PS spacers had a lower rate of mechanical complications and reoperation, better HSS knee scores, and greater ROM than CR spacers.

Development of mussel-inspired 3D-printed poly (lactic acid) scaffold grafted with bone morphogenetic protein-2 for stimulating osteogenesis.

3D printing is a versatile technique widely applied in tissue engineering due to its ability to manufacture large quantities of scaffolds or constructs with various desired architectures. In this study, we demonstrated that poly (lactic acid) (PLA) scaffolds fabricated via fused deposition not only retained the original interconnected microporous architectures, the scaffolds also exhibited lower lactic acid dissolution as compared to the freeze-PLA scaffold. The 3D-printed scaffolds were then grafted with human bone morphogenetic protein-2 (BMP-2) via the actions of polydopamine (PDA) coatings. The loading and release rate of BMP-2 were monitored for a period of 35 days. Cellular behaviors and osteogenic activities of co-cultured human mesenchymal stem cells (hMSCs) were assessed to determine for efficacies of scaffolds. In addition, we demonstrated that our fabricated scaffolds were homogenously coated with PDA and well grafted with BMP-2 (219.1 ± 20.4 ng) when treated with 250 ng/mL of BMP-2 and 741.4 ± 127.3 ng when treated with 1000 ng/mL of BMP-2. This grafting enables BMP-2 to be released in a sustained profile. From the osteogenic assay, it was shown that the ALP activity and osteocalcin of hMSCs cultured on BMP-2/PDA/PLA were significantly higher when compared with PLA and PDA/PLA scaffolds. The methodology of PDA coating employed in this study can be used as a simple model to immobilize multiple growth factors onto different 3D-printed scaffold substrates. Therefore, there is potential for generation of scaffolds with different unique modifications with different capabilities in regulating physiochemical and biological properties for future applications in bone tissue engineering.

3D-Printed Bioactive Calcium Silicate/Poly-ε-Caprolactone Bioscaffolds Modified with Biomimetic Extracellular Matrices for Bone Regeneration.

Currently, clinically available orthopedic implants are extremely biocompatible but they lack specific biological characteristics that allow for further interaction with surrounding tissues. The extracellular matrix (ECM)-coated scaffolds have received considerable interest for bone regeneration due to their ability in upregulating regenerative cellular behaviors. This study delves into the designing and fabrication of three-dimensional (3D)-printed scaffolds that were made out of calcium silicate (CS), polycaprolactone (PCL), and decellularized ECM (dECM) from MG63 cells, generating a promising bone tissue engineering strategy that revolves around the concept of enhancing osteogenesis by creating an osteoinductive microenvironment with osteogenesis-promoting dECM. We cultured MG63 on scaffolds to obtain a dECM-coated CS/PCL scaffold and further studied the biological performance of the dECM hybrid scaffolds. The results indicated that the dECM-coated CS/PCL scaffolds exhibited excellent biocompatibility and effectively enhanced cellular adhesion, proliferation, and differentiation of human Wharton's Jelly mesenchymal stem cells by increasing the expression of osteogenic-related genes. They also presented anti-inflammatory characteristics by showing a decrease in the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). Histological analysis of in vivo experiments presented excellent bone regenerative capabilities of the dECM-coated scaffold. Overall, our work presented a promising technique for producing bioscaffolds that can augment bone tissue regeneration in numerous aspects.

Effect of Strontium Substitution on the Physicochemical Properties and Bone Regeneration Potential of 3D Printed Calcium Silicate Scaffolds.

In this study, we synthesized strontium-contained calcium silicate (SrCS) powder and fabricated SrCS scaffolds with controlled precise structures using 3D printing techniques. SrCS scaffolds were shown to possess increased mechanical properties as compared to calcium silicate (CS) scaffolds. Our results showed that SrCS scaffolds had uniform interconnected macropores (~500 µm) with a compressive strength 2-times higher than that of CS scaffolds. The biological behaviors of SrCS scaffolds were assessed using the following characteristics: apatite-precipitating ability, cytocompatibility, proliferation, and osteogenic differentiation of human mesenchymal stem cells (MSCs). With CS scaffolds as controls, our results indicated that SrCS scaffolds demonstrated good apatite-forming bioactivity with sustained release of Si and Sr ions. The in vitro tests demonstrated that SrCS scaffolds possessed excellent biocompatibility which in turn stimulated adhesion, proliferation, and differentiation of MSCs. In addition, the SrCS scaffolds were able to enhance MSCs synthesis of osteoprotegerin (OPG) and suppress macrophage colony-stimulating factor (M-CSF) thus disrupting normal bone homeostasis which led to enhanced bone formation over bone resorption. Implanted SrCS scaffolds were able to promote new blood vessel growth and new bone regeneration within 4 weeks after implantation in critical-sized rabbit femur defects. Therefore, it was shown that 3D printed SrCS scaffolds with specific controllable structures can be fabricated and SrCS scaffolds had enhanced mechanical property and osteogenesis behavior which makes it a suitable potential candidate for bone regeneration.

Effects of bone morphogenic protein-2 loaded on the 3D-printed MesoCS scaffolds.

BACKGROUND/PURPOSE: The mesoporous calcium silicate (MesoCS) 3D-printed scaffold show excellent bioactivity and can enhance the bone-like apatite formation. The purpose of this study aims to consider the effects of the different loading methods on the novel grafting materials which composed of bone morphogenetic protein-2 (BMP-2) loaded MesoCS scaffold by employing 3D-printing technique. METHODS: The MesoCS scaffold were fabricated by fused deposition modeling. In this study, there are two methods of loading BMP-2: (1) the pre-loading (PL) method by mixing MesoCS and BMP-2 as a raw material for a 3D-printer, and (2) the direct-loading (DL) method by soaking the 3D-printed MesoCS scaffold in a BMP-2 solution. The characteristics of MesoCS scaffold were examined by transmission electron microscopy (TEM), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Their physical properties, biocompatibility, and osteogenic-related ability were also evaluated. RESULTS: The 3D MesoCS/PCL scaffolds showed excellent biocompatibility and physical properties. After soaking in simulated body fluid, the bone-like apatite layer of the PL and DL groups could be formed. In addition, the DL group released fifty percent more than the PL group at the end of the first day and PL showed a sustained release profile after 2 weeks. CONCLUSION: The 3D MesoCS/PCL porous scaffolds were successfully fabricated via a 3D printing system and were tested in vitro and were found to show good cellular activity for cell behavior although the PL method was not favorable for clinical application in relation with the preservation of BMP-2. With regards to different growth factor loading methods, this study demonstrated that PL of BMP-2 into MesoCS prior to printing will result in a more sustained drug release pattern as compared to traditional methods of scaffolds directly immersed with BMP-2.

Bioactive calcium silicate/poly-ε-caprolactone composite scaffolds 3D printed under mild conditions for bone tissue engineering.

The present study provides a solvent-free processing method for establishing the ideal porous 3-dimension (3D) scaffold filled with different ratios of calcium silicate-based (CS) powder and polycaprolactone (PCL) for 3D bone substitute application. Characterization of hybrid scaffolds developed underwent assessments for physicochemical properties and biodegradation. Adhesion and growth of human Wharton's Jelly mesenchymal stem cells (WJMSCs) on the CS/PCL blended scaffold were investigated in vitro. Cell attachment and morphology were examined by scanning electron microscope (SEM) and confocal microscope observations. Colorimetric assay was tested for assessing cell metabolic activity. In addition, RT-qPCR was also performed for the osteogenic-related and angiogenesis-related gene expression. As a result, the hydrophilicity of the scaffolds was further significantly improved after we additive CS into PCL, as well as the compressive strength up to 5.8 MPa. SEM showed that a great amount of precipitated bone-like apatite formed on the scaffold surface after immersed in the simulated body fluid. The 3D-printed scaffolds were found to enhance cell adhesion, proliferation and differentiation. Additionally, results of osteogenesis and angiogenesis proteins were expressed obviously greater in the response of WJMSCs. These results indicate the CS/PCL composite exhibited a favorable bioactivity and osteoconductive properties that could be served as a promising biomaterial for bone tissue engineering scaffolds.

Anti-inflammation performance of curcumin-loaded mesoporous calcium silicate cement.

BACKGROUND/PURPOSE: Calcium silicate (CS) cements have excellent bioactivity and can induce the bone-like apatite formation. They are good biomaterials for bone tissue engineering and bone regenerative medicine. However, they have degradability and the dissolved CS can cause the inflammatory response at the early post-implantation stage. The purpose of this study was to design and prepare the curcumin-loaded mesoporous CS (MesoCS/curcumin) cements as a strategy to reduce the inflammatory reaction after implantation. METHODS: The MesoCS/curcumin cements were designed and prepared. The characteristics of MesoCS/curcumin specimens were examined by transmission electron microscopy (TEM), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Their physical properties, biocompatibility, and anti-inflammatory ability were also evaluated. RESULTS: The MesoCS/curcumin cements displayed excellent biocompatibility and physical properties. Their crystalline characterizations were very similar with MesoCS cements. After soaking in simulated body fluid, the bone-like apatite layer of the MesoCS/curcumin cements could be formed. In addition, it could inhibit the expression of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) after inflammation reaction induced by lipopolysaccharides and had good anti-inflammatory ability. CONCLUSION: Adding curcumin in MesoCS cements can reduce the inflammatory reaction, but does not affect the original biological activity and properties of MesoCS cements. It can provide a good strategy to inhibit the inflammatory reaction after implantation for bone tissue engineering and bone regenerative medicine.

Can Early Rehabilitation Prevent Posttraumatic Osteoarthritis in the Patellofemoral Joint after Anterior Cruciate Ligament Rupture? Understanding the Pathological Features.

Knee instability resulting from anterior cruciate ligament (ACL) rupture is a high-risk factor for posttraumatic osteoarthritis (PTOA) in the patellofemoral joint (PFJ). However, whether non-weight-bearing and weight-bearing treatments have chondroprotective effects remains unclear. Twenty-four adult New Zealand White male rabbits were employed in this study. All animals received ACL transection in the right knee and sham surgery in the left knee. The rabbits were randomly assigned to the following groups: (I) In the sedentary (SED) group, the rabbits (n = 6) were simply kept in their cage; (II) In the continuous passive motion (CPM) group, the rabbits (n = 6) performed CPM exercise for 7 days, starting from the first postoperative day; (III) In the active treadmill exercise (TRE) group, the rabbits (n = 6) performed TRE for 2 weeks; (IV) In the CPM + TRE group, the rabbits (n = 6) executed CPM exercise, followed by TRE. Two joint surfaces (the retropatella and femoral trochlear groove) were assessed at 4 weeks after operation. Although the gross appearance in each group was comparable, histological examination revealed significant differences in the articular cartilage status. The CPM group exhibited a greater thickness of articular cartilage, maintenance of tidemark continuity, abundant glycosaminoglycan (GAG), and significantly lower inflammatory cytokine 9, e.g., tumor necrosis factor-alpha (TNF-α) 0 levels, with modest cell apoptosis (i.e., caspase-3). By contrast, the TRE group displayed the worst pathological features: an irregular cartilage surface and chondrocyte disorganization, reduced cartilage thickness, breakdown of the tidemark, depletion of collagen fibers, loss of GAG, and the highest levels of TNF-α and caspase-3 expression. Furthermore, the CPM + TRE group had more favorable outcomes than the SED group, indicating that suitable exercise is needed. The sham treatment displayed no variance in the changes in the two joint surfaces among groups. These data indicate that the application of early CPM rehabilitation is suggested for subjects in order to decrease the risk of PTOA without ACL reconstruction in the PFJ compartment in rabbits. The early TRE program, however, had harmful outcomes. Additionally, inactivity was discovered to initiate the development of PTOA.

Tensile force on human macrophage cells promotes osteoclastogenesis through receptor activator of nuclear factor κB ligand induction.

Little is known about the effects of tensile forces on osteoclastogenesis by human monocytes in the absence of mechanosensitive cells, including osteoblasts and fibroblasts. In this study we consider the effects of tensile force on osteoclastogenesis in human monocytes. The cells were treated with receptor activator of nuclear factor κB ligand (RANKL) to promote osteoclastogenesis. Then,expression and secretion of cathepsin K were examined. RANKL and the formation of osteoclasts during the osteoclast differentiation process under continual tensile stress were evaluated by Western blot. It was also found that -100 kPa or lower induces RANKL-enhanced tartrate-resistant acid phosphatase activity in a dose-dependent manner. Furthermore, an increased tensile force raises the expression and secretion of cathepsin K elevated by RANKL, and is concurrent with the increase of TNF-receptor-associated factor 6 induction and nuclear factor κB activation. Overall, the current report demonstrates that tensile force reinforces RANKL-induced osteoclastogenesis by retarding osteoclast differentiation. The tensile force is able to modify every cell through dose-dependent in vitro RANKL-mediated osteoclastogenesis, affecting the fusion of preosteoclasts and function of osteoclasts. However, tensile force increased TNF-receptor-associated factor 6 expression. These results are in vitro findings and were obtained under a condition of tensile force. The current results help us to better understand the cellular roles of human macrophage populations in osteoclastogenesis as well as in alveolar bone remodeling when there is tensile stress.

Macrophage-mediated osteogenesis activation in co-culture with osteoblast on calcium silicate cement.

The use of calcium silicate (CS) cement holds great promise for bone substitute biomaterials. However, the effects of CS on osteoblast and macrophage cells are not fully understood. This study examines cell proliferation and differentiation of mono- or co-cultured MC3T3-E1 and Raw 264.7 cells on CS cement. Very few studies to date have looked at the effects of osteoblast and macrophages on biomaterial-regulated osteogenesis. In this study the proliferation and differentiation of MC3T3-E1, Raw 264.7 and co-cultured MC3T3-E1/Raw 264.7 on CS cements have been analyzed using a PrestoBlue kit and ELISA. In addition, the effect of macrophages on CS-coordinated osteogenesis of MC3T3-E1 has been investigated. Results show that MC3T3-E1, Raw 264.7 and co-cultured MC3T3-E1/Raw 264.7 adhere to and proliferate well on the CS cement. In a co-culture, the CS cements inhibit receptor activator of nuclear factor kappa B ligand expression of both genes and proteins in Raw 264.7 cells when compared to those grown in mono-cultured system. Ca deposition of MC3T3-E1 in the co-culture is higher than that of cells in a mono-culture. Bone morphogenetic protein 2 (BMP2) is also significantly up-regulated by the CS cement stimulation, indicating that macrophages may participate in the CS stimulated osteogenesis. Interestingly, when macrophage are cultured with BMP2 receptor-blocking MC3T3-E1 on the CS cements, the osteogenesis differentiation of the cells is significantly inhibited, indicating the important role of macrophages in biomaterial-induced osteogenesis via BMP2 receptors. It is assumed that it is an increase in the secretion of the BMP2 from the Raw 264.7 cell that is primarily involved in the promotion of the osteogenesis of the MC3T3-E1. These results provide valuable insights into both the mechanism of CS-stimulated osteogenesis, and strategies to optimize the evaluation system for the in vitro osteogenesis capacity of bone substitute biomaterials.

The synergistic effects of Chinese herb and injectable calcium silicate/ß-tricalcium phosphate composite on an osteogenic accelerator in vitro.

This study investigates the physicochemical and biological effects of traditional Chinese medicines on the ß-tricalcium phosphate (ß-TCP)/calcium silicate (CS) composites of bone cells using human dental pulp cell. CS is an osteoconductive and bioactive material. For this research we have combined ß-TCP and CS and check its effectiveness, a series of ß-TCP/CS composites with different ratios of Xu Duan (XD) were prepared to make new bioactive and biodegradable biocomposites for bone repair. XD has been used in Traditional Chinese Medicine for hundreds of years as an antiosteoporosis, tonic and antiaging agent for the therapy of low back pain, traumatic hematoma, threatened abortion and bone fractures. Formation of bone-like apatite, the diametral tensile strength, and weight loss of composites were considered before and after immersion in simulated body fluid (SBF). In addition, we also examined the effects of XD released from ß-TCP/CS composites and in vitro human dental pulp cell (hDPCs) and studied its behavior. The results show the XD-contained paste did not give any demixing when the weight ratio of XD increased to 5-10 % due to the filter-pressing effect during extrusion through the syringe. After immersion in SBF, the microstructure image showed a dense bone-like apatite layer covered on the ß-TCP/CS/XD composites. In vitro cell experiments shows that the XD-rich composites promote human dental pulp cells (hDPCs) proliferation and differentiation. However, when the XD quantity in the composite is more than 5 %, the amount of cells and osteogenesis protein of hDPCs were stimulated by XD released from ß-TCP/CS composites. The combination of XD in degradation of ß-TCP and osteogenesis of CS gives strong reason to believe that these calcium-based composite cements may prove to be promising bone repair materials.

Activation of focal adhesion kinase induces extracellular signal-regulated kinase-mediated osteogenesis in tensile force-subjected periodontal ligament fibroblasts but not in osteoblasts.

The exact mechanism by which focal adhesion kinase (FAK) translates mechanical signals into osteogenesis differentiation in force-subjected cells has not been elucidated. The responses to different forces differ according to the origin of cells and the type of stress applied. Therefore, the recruitment of osteoclast and osteoblast progenitor cells, and the balanced activation of these cells around and within the periodontal ligament (PDL) are essential for alveolar bone remodeling. Cells within the PDL and MG63 cells were subjected to tensile forces of -100 kPa for different periods of time. At various times during the tensile force application, they were processed for the purpose of analyzing cell viability, cell cycle, and osteogenic protein. The effect of small interfering RNA transfection targeting FAK was also evaluated. Tensile force enhanced a rapid increase in the phosphorylation of FAK and up-regulated osteogenic protein expression in PDL cells, but not in MG63 cells. Transfecting PDL cells with FAK antisense oligonucleotide diminished alkaline phosphatase and osteocalcin secretion. These findings suggest that tensile force activates FAK pathways in PDL cells, which down-regulate immune cytokine and up-regulate osteogenic protein.

Correction: Additive manufacturing of barium-doped calcium silicate/poly-ε-caprolactone scaffolds to activate CaSR and AKT signalling and osteogenic differentiation of mesenchymal stem cells.

Correction for 'Additive manufacturing of barium-doped calcium silicate/poly-ε-caprolactone scaffolds to activate CaSR and AKT signalling and osteogenic differentiation of mesenchymal stem cells' by Yung-Cheng Chiu et al., J. Mater. Chem. B, 2023, 11, 4666-4676, https://doi.org/10.1039/D3TB00208J.

Additive manufacturing of barium-doped calcium silicate/poly-ε-caprolactone scaffolds to activate CaSR and AKT signalling and osteogenic differentiation of mesenchymal stem cells.

3D-printed scaffolds are suitable for patient-specific implant preparation for bone regeneration in large-scale critical bone defects. In addition, these scaffolds should have mechanical and biological properties similar to those of natural bone tissue. In this study, 3D-printed barium-doped calcium silicate (BaCS)/poly-ε-caprolactone (PCL) composite scaffolds were fabricated as an alternative strategy for bone tissue engineering to achieve appropriate physicochemical characteristics and stimulate osteogenesis. Scaffolds containing 10% Ba (Ba10) showed optimal mechanical properties, preventing premature scaffold degradation during immersion while enabling ion release in a sustained manner to achieve the desired therapeutic goals. In addition, Wharton's jelly mesenchymal stem cells (WJMSCs) were used to assess biocompatibility and osteogenic differentiation behaviour. WJMSCs were cultured on the scaffold and permeabilised via ICP to analyse the presence of Si and Ba ions in the medium and cell lysates, suggesting that the ions released by the scaffold could effectively enter the cells. The protein expression of CaSR, PI3K, Akt, and JNK confirmed that CaSR could activate cells cultured in Ba10, thereby affecting the subsequent PI3k/Akt and JNK pathways and further promoting osteogenic differentiation. The in vivo performance of the proposed scaffolds was assessed using micro-CT and histological slices, which revealed that the BaCS scaffolds could further enhance bone regeneration, compared with bare scaffolds. These results suggest the potential use of 3D-printed BaCS/PCL scaffolds as next-generation substitutes for bone regeneration.

3D-biofabricated chondrocyte-laden decellularized extracellular matrix-contained gelatin methacrylate auxetic scaffolds under cyclic tensile stimulation for cartilage regeneration.

Three-dimensional (3D) hydrogel constructs can mimic features of the extracellular matrix (ECM) and have tailorable physicochemical properties to support and maintain the regeneration of articular cartilage. Various studies have shown that mechanical cues affect the cellular microenvironment and thereby influence cellular behavior. In this study, we fabricated an auxetic scaffold to investigate the effect of 3D tensile stimulation on chondrocyte behavior. Different concentrations of decellularized extracellular matrix (dECM) were mixed with fish gelatin methacrylate (FGelMa) and employed for the preparation of dECM/FGelMa auxetic bio-scaffolds using 3D biofabrication technology. We show that when human chondrocytes (HCs) were incorporated into these scaffolds, their proliferation and the expression of chondrogenesis-related markers increased with dECM content. The function of HC was influenced by cyclic tensile stimulation, as shown by increased production of the chondrogenesis-related markers, collagen II and glycosaminoglycans, with the involvement of the yes-associated protein 1 signaling pathway. The biofabricated auxetic scaffold represents an excellent platform for exploring interactions between cells and their mechanical microenvironment.

Additive manufacturing of Schwann cell-laden collagen/alginate nerve guidance conduits by freeform reversible embedding regulate neurogenesis via exosomes secretion towards peripheral nerve regeneration.

Peripheral nerve injury is a common clinical problem that could be debilitating to one's quality of life. The complex nerve guidance conduits (NGCs) with cells in order to improve nerve regeneration. Therefore, we used freeform reversible embedding of suspended hydrogels to fabricate Schwann cells (SCs)-laden collagen/alginate (Col/Alg) NGCs. First, we evaluated Col influence on the characteristics of NGCs. After which, Wharton's jelly mesenchymal stem cells (WJMSC) are seeded onto the inner channel of NGCs and evaluated neural regeneration behaviors. Results indicated the SCs-laden NGCs with 2.5 % Col found the highest proliferation and secretion of neurotrophic protein. Furthermore, co-culture of SCs promoted differentiation of WJMSC as seen from the increased neurogenic-related protein in NGCs. To determine the molecular mechanism between SCs and WJMSC, we demonstrated the neurotrophic factors secreted by SCs act on tropomyosin receptor kinase A (TrkA) receptors of WJMSC to promote nerve regeneration. In addition, our study demonstrated SCs-derived exosomes had a critical role in regulating neural differentiation of WJMSC. Taken together, this study demonstrates the fabrication of SCs-laden Col/Alg NGCs for nerve regeneration and understanding regarding the synergistic regenerative mechanisms of different cells could bring us a step closer for clinical treatment of large nerve defects.

A novel label-free electrochemical immunosensor for the detection of heat shock protein 70 of lung adenocarcinoma cell line following paclitaxel treatment using l-cysteine-functionalized Au@MnO2/MoO3 nanocomposites.

The future trend in achieving precision medicine involves the development of non-invasive cancer biomarker sensors that offer high accuracy, low cost, and time-saving benefits for risk clarification, early detection, disease detection, and therapeutic monitoring. A facile approach for the synthesis of MoO3 nanosheets was developed by thermally oxidizing MoS2 nanosheets in air followed by thermal annealing. Subsequently, Au@MnO2 nanocomposites were prepared using a combined hydrothermal process and in situ chemical synthesis. In this study, we present a novel immunosensor design strategy involving the immobilization of antiHSP70 antibodies on Au@MnO2/MoO3 nanocomposites modified on a screen-printed electrode (SPE) using EDC/NHS chemistry. This study establishes HSP70 as a potential biomarker for monitoring therapeutic response during anticancer therapy. Impedance measurements of HSP70 on the Au@MnO2/MoO3/SPE immunosensor using EIS showed an increase in impedance with an increase in HSP70 concentration. The electrochemical immunosensor demonstrated a good linear response in the range of 0.001 to 1000 ng mL-1 with a detection limit of 0.17 pg mL-1 under optimal conditions. Moreover, the immunosensor was effective in detecting HSP70 at low concentrations in a lung adenocarcinoma cell line following Paclitaxel treatment, indicating its potential for early detection of the HSP70 biomarker in organ-on-a-chip and clinical applications.

The exosomal secretomes of mesenchymal stem cells extracted via 3D-printed lithium-doped calcium silicate scaffolds promote osteochondral regeneration.

The development of surface modification techniques has brought about a major paradigm shift in the clinical applications of bone tissue regeneration. Biofabrication strategies enable the creation of scaffolds with specific microstructural environments and biological components. Lithium (Li) has been reported to exhibit anti-inflammatory, osteogenic, and chondrogenic properties by promoting several intracellular signaling pathways. Currently, research focuses on fabricating scaffolds with simultaneous dual bioactivities to enhance osteochondral regeneration. In this study, we modified the surface of calcium silicate (CS) scaffolds with Li using a simple immersion technique and evaluated their capabilities for bone regeneration. The results showed that Li ions could be easily coated onto the surfaces of CS scaffolds without affecting the microstructural properties of CS itself. Furthermore, the modifications did not affect the printing capabilities of the CS, and porous scaffolds could be fabricated via extrusion. Moreover, the presence of Li improved the surface roughness and hydrophilicity, thus leading to enhanced secretion of osteochondral-related regeneration factors, such as alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen II (Col II) proteins. Subsequent in vivo studies, including histological and micro-CT analyses, confirmed that the Li-modified CS scaffolds promoted osteochondral regeneration. The transcriptome analysis suggested that the enhanced osteochondrogenic capabilities of our scaffolds were influenced by paracrine exosomes. We hope this study will inspire further research on osteochondral regeneration.