The Synergistic Effect of Electrical Stimulation and Dermal Fibroblast Cells-Laden 3D Conductive Hydrogel for Full-Thickness Wound Healing.

Clinically, most patients with poor wound healing suffer from generalized skin damage, usually accompanied by other complications, so developing therapeutic strategies for difficult wound healing has remained extremely challenging until now. Current studies have indicated that electrical stimulation (ES) to cutaneous lesions enhances skin regeneration by activating intracellular signaling cascades and secreting skin regeneration-related cytokine. In this study, we designed different concentrations of graphene in gelatin-methacrylate (GelMa) to form the conductive composite commonly used in wound healing because of its efficiency compared to other conductive thermo-elastic materials. The results demonstrated the successful addition of graphene to GelMa while retaining the original physicochemical properties of the GelMa bioink. In addition, the incorporation of graphene increased the interactions between these two biomaterials, leading to an increase in mechanical properties, improvement in the swelling ratio, and the regulation of degradation characteristics of the biocomposite scaffolds. Moreover, the scaffolds exhibited excellent electrical conductivity, increasing proliferation and wound healing-related growth factor secretion from human dermal fibroblasts. Overall, the HDF-laden 3D electroconductive GelMa/graphene-based hydrogels developed in this study are ideal biomaterials for skin regeneration applications in the future.

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.

Genome-wide methylation profiles in coronary artery ectasia.

Coronary artery ectasia (CAE) is a disease characterized by abnormally dilated coronary arteries. The mechanism of CAE remains unclear, and its treatment is limited. Previous studies have shown that risk factors for CAE were related to changes in DNA methylation. However, no systematic investigation of methylation profiles has been performed. Therefore, we compared methylation profiles between 12 CAE patients and 12 propensity-matched individuals with normal coronary arteries using microarrays. Wilcoxon's rank sum tests revealed 89 genes with significantly different methylation levels (P<0.05 and Δß > |0.1|). Functional characterization using the DAVID database and gene set enrichment analysis indicated that these genes were involved in immune and inflammatory responses. Of these genes 6 were validated in 29 CAE patients and 87 matched individuals with CAE, using pyro-sequencing. TLR6 and NOTCH4 showed significant differences in methylation between the two groups, and lower protein levels of toll-like receptor 6 (TLR6) were detected in CAE patients. In conclusion, this genome-wide analysis of methylation profiles in CAE patients showed that significant changes in both methylation and expression of TLR6 deserve further study to elucidate their roles in CAE.

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.

Enhancing the Mechanical Properties and Aging Resistance of 3D-Printed Polyurethane through Polydopamine and Graphene Coating.

Three-dimensional (3D) printing is a versatile manufacturing method widely used in various industries due to its design flexibility, rapid production, and mechanical strength. Polyurethane (PU) is a biopolymer frequently employed in 3D printing applications, but its susceptibility to UV degradation limits its durability. To address this issue, various additives, including graphene, have been explored to enhance PU properties. Graphene, a two-dimensional carbon material, possesses remarkable mechanical and electrical properties, but challenges arise in its dispersion within the polymer matrix. Surface modification techniques, like polydopamine (PDA) coating, have been introduced to improve graphene's compatibility with polymers. This study presents a method of 3D printing PU scaffolds coated with PDA and graphene for enhanced UV stability. The scaffolds were characterized through X-ray diffraction, Fourier-transform infrared spectroscopy, mechanical testing, scanning electron microscopy, and UV durability tests. Results showed successful PDA coating, graphene deposition, and improved mechanical properties. The PDA-graphene-modified scaffolds exhibited greater UV resistance over time, attributed to synergistic effects between PDA and graphene. These findings highlight the potential of combining PDA and graphene to enhance the stability and mechanical performance of 3D-printed PU scaffolds.

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.

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.

The Synergistic Effect of Cyclic Tensile Force and Periodontal Ligament Cell-Laden Calcium Silicate/Gelatin Methacrylate Auxetic Hydrogel Scaffolds for Bone Regeneration.

The development of 3D printing technologies has allowed us to fabricate complex novel scaffolds for bone regeneration. In this study, we reported the incorporation of different concentrations of calcium silicate (CS) powder into fish gelatin methacrylate (FGelMa) for the fabrication of CS/FGelMa auxetic bio-scaffolds using 3D printing technology. Our results showed that CS could be successfully incorporated into FGelMa without influencing the original structural components of FGelMa. Furthermore, it conveyed that CS modifications both the mechanical properties and degradation rates of the scaffolds were improved in accordance with the concentrations of CS upon modifications of CS. In addition, the presence of CS enhanced the adhesion and proliferation of human periodontal ligament cells (hPDLs) cultured in the scaffold. Further osteogenic evaluation also confirmed that CS was able to enhance the osteogenic capabilities via activation of downstream intracellular factors such as pFAK/FAK and pERK/ERK. More interestingly, it was noted that the application of extrinsic biomechanical stimulation to the auxetic scaffolds further enhanced the proliferation and differentiation of hPDLs cells and secretion of osteogenic-related markers when compared to CS/FGelMa hydrogels without tensile stimulation. This prompted us to explore the related mechanism behind this interesting phenomenon. Subsequent studies showed that biomechanical stimulation works via YAP, which is a biomechanical cue. Taken together, our results showed that novel auxetic scaffolds could be fabricated by combining different aspects of science and technology, in order to improve the future chances of clinical applications for bone regeneration.

The effects of a 3D-printed magnesium-/strontium-doped calcium silicate scaffold on regulation of bone regeneration via dual-stimulation of the AKT and WNT signaling pathways.

Numerous studies have demonstrated that calcium silicate (CS) can be doped with various trace metal elements such as strontium (Sr) or magnesium (Mg). These studies have confirmed that such modifications promote bone regeneration. However, the development and emergence of 3D printing have further made it possible to fabricate bone grafts with precise structural designs using multi-bioceramics so as to better suit specific clinical requirements. We fabricated scaffolds using Mg-doped CS as the outer layer with Sr-doped CS in the center. In addition, PCL was used to improve printability of the scaffolds. This enhanced Mg and Sr architecture prevented premature degradation of the scaffolds during immersion while enabling the release of ions in a sustained manner in order to achieve the desired therapeutic goals. Even the capabilities of stem cells were shown to be enhanced when cultured on these scaffolds. Furthermore, the hybrid scaffolds were found to up-regulate the expression of bone-related proteins such as factors leading to differentiation-inducing pathways, including PI3K/Akt, Wnt, and TRPM7. The in vivo performance of the proposed scaffolds was assessed using micro-CT. The histological results revealed that the hybrid scaffolds were able to further enhance bone regeneration as compared to uni-bioceramics. By combining 3D printing, multi-ceramics, and trace metal elements, a novel hybrid scaffold could be fabricated with ease and specifically suited to future bone tissue engineering applications.

Effect of mussel-inspired polydopamine on the reinforced properties of 3D printed ß-tricalcium phosphate/polycaprolactone scaffolds for bone regeneration.

Bioceramic/polymer scaffolds have been considered as potential grafts used for facilitating bone healing. Unfortunately, the poor interfacial interaction between polymer matrices and bioceramic fillers limited their use in practical medicine. Thus, a facile strategy for reinforcing the three-dimensional printed ß-tricalcium phosphate/polycaprolactone scaffolds through employing polydopamine modified-ceramics as fillers. The effects of the dopamine precursor on the compressive strength, degradability, cell proliferation, osteogenic differentiation, and in vivo osteogenicity were measured. The results indicated that the concentration of dopamine could remarkably affect the thickness and density of the polydopamine layer on fillers, further varying the compressive strength (1.23-fold to 1.64-fold), degradability, and osteogenicity of the scaffolds. More importantly, the presence of polydopamine in the three-dimensional printed composite scaffolds not only facilitated the proliferation, alkaline phosphatase activity and mineralization of mesenchymal stem cells, but also stimulated the formation of neo-bone tissue in femur defects. Taking together, the proposed scaffolds might serve as a candidate for bone regeneration.

Synergistic Effect of Static Magnetic Fields and 3D-Printed Iron-Oxide-Nanoparticle-Containing Calcium Silicate/Poly-ε-Caprolactone Scaffolds for Bone Tissue Engineering.

In scaffold-regulated bone regeneration, most three-dimensional (3D)-printed scaffolds do not provide physical stimulation to stem cells. In this study, a magnetic scaffold was fabricated using fused deposition modeling with calcium silicate (CS), iron oxide nanoparticles (Fe3O4), and poly-ε-caprolactone (PCL) as the matrix for internal magnetic sources. A static magnetic field was used as an external magnetic source. It was observed that 5% Fe3O4 provided a favorable combination of compressive strength (9.6 ± 0.9 MPa) and degradation rate (21.6 ± 1.9% for four weeks). Furthermore, the Fe3O4-containing scaffold increased in vitro bioactivity and Wharton's jelly mesenchymal stem cells' (WJMSCs) adhesion. Moreover, it was shown that the Fe3O4-containing scaffold enhanced WJMSCs' proliferation, alkaline phosphatase activity, and the osteogenic-related proteins of the scaffold. Under the synergistic effect of the static magnetic field, the CS scaffold containing Fe3O4 can not only enhance cell activity but also stimulate the simultaneous secretion of collagen I and osteocalcin. Overall, our results demonstrated that Fe3O4-containing CS/PCL scaffolds could be fabricated three dimensionally and combined with a static magnetic field to affect cell behaviors, potentially increasing the likelihood of clinical applications for bone tissue engineering.

Combined Effects of Polydopamine-Assisted Copper Immobilization on 3D-Printed Porous Ti6Al4V Scaffold for Angiogenic and Osteogenic Bone Regeneration.

Numerous studies have demonstrated that biological compounds and trace elements such as dopamine (DA) and copper ions (Cu) could be modified onto the surfaces of scaffolds using a one-step immersion process which is simple, inexpensive and, most importantly, non-cytotoxic. The development and emergence of 3D printing technologies such as selective laser melting (SLM) have also made it possible for us to fabricate bone scaffolds with precise structural designs using metallic compounds. In this study, we fabricated porous titanium scaffolds (Ti) using SLM and modified the surface of Ti with polydopamine (PDA) and Cu. There are currently no other reported studies with such a combination for osteogenic and angiogenic-related applications. Results showed that such modifications did not affect general appearances and microstructural characteristics of the porous Ti scaffolds. This one-step immersion modification allowed us to modify the surfaces of Ti with different concentrations of Cu ions, thus allowing us to fabricate individualized scaffolds for different clinical scenarios. The modification improved the hydrophilicity and surface roughness of the scaffolds, which in turn led to promote cell behaviors of Wharton's jelly mesenchymal stem cells. Ti itself has high mechanical strength, therefore making it suitable for surgical handling and clinical applications. Furthermore, the scaffolds were able to release ions in a sustained manner which led to an upregulation of osteogenic-related proteins (bone alkaline phosphatase, bone sialoprotein and osteocalcin) and angiogenic-related proteins (vascular endothelial growth factor and angiopoietin-1). By combining additive manufacturing, Ti6Al4V scaffolds, surface modification and Cu ions, the novel hybrid 3D-printed porous scaffold could be fabricated with ease and specifically benefited future bone regeneration in the clinic.

The 3D printed conductive grooved topography hydrogel combined with electrical stimulation for synergistically enhancing wound healing of dermal fibroblast cells.

Patients with extensive cutaneous damage resulting from poor wound healing often have other comorbidities such as diabetes that may lead to impaired skin functions and scar formation. Many recent studies have shown that the application of electrical stimulation (ES) to cutaneous lesions significantly improves skin regeneration via activation of AKT intracellular signaling cascades and secretion of regeneration-related growth factors. In this study, we fabricated varying concentrations of gelatin-methacrylate (GelMa) hydrogels with poly(3,4-ethylenedioxythiophene) (PEDOT): polystyrene sulfonate (PSS), which is a conductive material commonly used in tissue engineering due to its efficiency among conductive thermo-elastic materials. The results showed successful modification of PEDOT:PSS with GelMa while retaining the original structural characteristics of the GelMa hydrogels. In addition, the incorporation of PEDOT:PSS increased the interactions between both the materials, thus leading to enhanced mechanical strength, improved swelling ratio, and decreased hydrophilicity of the scaffolds. Our GelMa/PEDOT:PSS scaffolds were designed to have micro-grooves on the surfaces of the scaffolds for the purpose of directional guiding. In addition, our scaffolds were shown to have excellent electrical conductivity, thus leading to enhanced cellular proliferation and directional migration and orientation of human dermal fibroblasts. In vivo studies revealed that the GelMa/PEDOT:PSS scaffolds with electrical stimulation were able to induce full skin thickness regeneration, as seen from the various stainings. These results indicate the potential of GelMa/PEDOT:PSS as an electro-conductive biomaterial for future skin regeneration applications.

Therapeutic Effects of the Addition of Fibroblast Growth Factor-2 to Biodegradable Gelatin/Magnesium-Doped Calcium Silicate Hybrid 3D-Printed Scaffold with Enhanced Osteogenic Capabilities for Critical Bone Defect Restoration.

Worldwide, the number of bone fractures due to traumatic and accidental injuries is increasing exponentially. In fact, repairing critical large bone defects remains challenging due to a high risk of delayed union or even nonunion. Among the many bioceramics available for clinical use, calcium silicate-based (CS) bioceramics have gained popularity due to their good bioactivity and ability to stimulate cell behavior. In order to improve the shortcomings of 3D-printed ceramic scaffolds, which do not easily carry growth factors and do not provide good tissue regeneration effects, the aim of this study was to use a gelatin-coated 3D-printed magnesium-doped calcium silicate (MgCS) scaffold with genipin cross-linking for regulating degradation, improving mechanical properties, and enhancing osteogenesis behavior. In addition, we consider the effects of fibroblast growth factor-2 (FGF-2) loaded into an MgCS scaffold with and without gelatin coating. Furthermore, we cultured the human Wharton jelly-derived mesenchymal stem cells (WJMSC) on the scaffolds and observed the biocompatibility, alkaline phosphatase activity, and osteogenic-related markers. Finally, the in vivo performance was assessed using micro-CT and histological data that revealed that the hybrid bioscaffolds were able to further achieve more effective bone tissue regeneration than has been the case in the past. The above results demonstrated that this type of processing had great potential for future clinical applications and studies and can be used as a potential alternative for future bone tissue engineering research, as well as having good potential for clinical applications.

Digital Light Processing Bioprinted Human Chondrocyte-Laden Poly (γ-Glutamic Acid)/Hyaluronic Acid Bio-Ink towards Cartilage Tissue Engineering.

Cartilage injury is the main cause of disability in the United States, and it has been projected that cartilage injury caused by osteoarthritis will affect 30% of the entire United States population by the year 2030. In this study, we modified hyaluronic acid (HA) with γ-poly(glutamic) acid (γ-PGA), both of which are common biomaterials used in cartilage engineering, in an attempt to evaluate them for their potential in promoting cartilage regeneration. As seen from the results, γ-PGA-GMA and HA, with glycidyl methacrylate (GMA) as the photo-crosslinker, could be successfully fabricated while retaining the structural characteristics of γ-PGA and HA. In addition, the storage moduli and loss moduli of the hydrogels were consistent throughout the curing durations. However, it was noted that the modification enhanced the mechanical properties, the swelling equilibrium rate, and cellular proliferation, and significantly improved secretion of cartilage regeneration-related proteins such as glycosaminoglycan (GAG) and type II collagen (Col II). The cartilage tissue proof with Alcian blue further demonstrated that the modification of γ-PGA with HA exhibited suitability for cartilage tissue regeneration and displayed potential for future cartilage tissue engineering applications. This study built on the previous works involving HA and further showed that there are unlimited ways to modify various biomaterials in order to further bring cartilage tissue engineering to the next level.

The synergistic effects of Xu Duan combined Sr-contained calcium silicate/poly-ε-caprolactone scaffolds for the promotion of osteogenesis marker expression and the induction of bone regeneration in osteoporosis.

Osteoporosis and its related problems such as fractures are gradually becoming common due to an aging population. Current methods to treat osteoporosis include medical and surgical options such as bone implants. Recent developments in 3D printing and materials science technologies has allowed us to fabricate individualized scaffolds with desired properties. In this study, we mixed Xu Duan into strontium­calcium silicate powder at 5% (XD5) and 10% (XD10) and fabricated 3D scaffolds with polycaprolactone. All scaffolds were assessed for its physical, mechanical, and biological properties to evaluated for its feasibility for bone tissue engineering in the osteoporosis model. Our results showed that such a scaffold could be fabricated using extrusion-based printing techniques and that addition of XD did not alter original structural properties of the SrCS. Furthermore, the XD5 and XD10 scaffolds were found to be non-toxic to cells and cells cultured on the scaffolds had significantly higher proliferation and secreted increased osteogenic-related proteins in in vitro studies as compared to the XD0 groups. Remarkably, the XD10 scaffolds could be used as substitutes for the critical-sized bone defect (7.0 mm diameter and 8.0 mm depth) in the osteoporotic rabbit model. The XD10 scaffolds can enhance bone ingrowth and accelerate new bone regeneration even in complex osteoporotic pathological environments. These results showed that such a Chinese medicine-contained scaffold had potential in osteoporosis bone tissue regeneration and could be considered as a promising tool for future clinical used applications.