Hybrid Scaffolds Research Articles

Chondrogenesis of mesenchymal stromal cells on the 3D printed polycaprolactone/fibrin/decellular cartilage matrix hybrid scaffolds in the presence of piascledine

Nowadays, cartilage tissue engineering (CTE) is considered important due to lack of repair of cartilaginous lesions and the absence of appropriate methods for treatment. In this study, polycaprolactone (PCL) scaffolds were fabricated by three-dimensional (3D) printing and were then coated with fibrin (F) and acellular solubilized extracellular matrix (ECM). After extracting adipose-derived stem cells (ADSCs), 3D-printed scaffolds were characterized and compared to hydrogel groups. After inducing the chondrogenic differentiation in the presence of Piascledine and comparing it with TGF-β3 for 28 days, the expression of genes involved in chondrogenesis (AGG, COLII) and the expression of the hypertrophic gene (COLX) were examined by real-time PCR. The expression of proteins COLII and COLX was also determined by immunohistochemistry. Glycosaminoglycan was measured by toluidine blue staining. 3D-printed scaffolds clearly improved cell proliferation, viability, water absorption and compressive strength compared to the hydrogel groups. Moreover, the use of compounds such as ECM and Piascledine in the process of ADSCs chondrogenesis induction increased cartilage-specific markers and decreased the hypertrophic marker compared to TGF-β3. In Piascledine groups, the expression of COLL II protein, COLL II and Aggrecan genes, and the amount of glycosaminoglycan showed a significant increase in the PCL/F/ECM compared to the PCL and PCL/F groups.

3D printed hybrid scaffolds do not induce adverse inflammation in mice and direct human BM-MSC chondrogenesis in vitro

Biomaterials that can improve the healing of articular cartilage lesions are needed. To address this unmet need, we developed novel 3D printed silica/poly(tetrahydrofuran)/poly(ε-caprolactone) (SiO2/PTHF/PCL-diCOOH) hybrid scaffolds. Our aim was to carry out essential studies to advance this medical device towards functional validation in pre-clinical trials. First, we show that the chemical composition, microarchitecture and mechanical properties of these scaffolds were not affected by sterilisation with gamma irradiation. To evaluate the systemic and local immunogenic reactivity of the sterilised 3D printed hybrid scaffolds, they were implanted subcutaneously into Balb/c mice. The scaffolds did not trigger a systemic inflammatory response over one week of implantation. The interaction between the host immune system and the implanted scaffold elicited a local physiological reaction with infiltration of mononuclear cells without any signs of a chronic inflammatory response.Then, we investigated how these 3D printed hybrid scaffolds direct chondrogenesis in vitro. Human bone marrow-derived mesenchymal stem/stromal cells (hBM-MSCs) seeded within the 3D printed hybrid scaffolds were cultured under normoxic or hypoxic conditions, with or without chondrogenic supplements. Chondrogenic differentiation assessed by both gene expression and protein production analyses showed that 3D printed hybrid scaffolds support hBM-MSC chondrogenesis. Articular cartilage-specific extracellular matrix deposition within these scaffolds was enhanced under hypoxic conditions (1.7 or 3.7 fold increase in the median of aggrecan production in basal or chondrogenic differentiation media).Our findings show that 3D printed SiO2/PTHF/PCL-diCOOH hybrid scaffolds have the potential to support the regeneration of cartilage tissue.

Three-Dimensional Bioprinting in Vascular Tissue Engineering and Tissue Vascularization of Cardiovascular Diseases.

In the 21st century, significant progress has been made in repairing damaged materials through material engineering. However, the creation of large-scale artificial materials still faces a major challenge in achieving proper vascularization. To address this issue, researchers have turned to biomaterials and three-dimensional (3D) bioprinting techniques, which allow for the combination of multiple biomaterials with improved mechanical and biological properties that mimic natural materials. Hydrogels, known for their ability to support living cells and biological components, have played a crucial role in this research. Among the recent developments, 3D bioprinting has emerged as a promising tool for constructing hybrid scaffolds. However, there are several challenges in the field of bioprinting, including the need for nanoscale biomimicry, the formulation of hydrogel blends, and the ongoing complexity of vascularizing biomaterials, which requires further research. On a positive note, 3D bioprinting offers a solution to the vascularization problem due to its precise spatial control, scalability, and reproducibility compared with traditional fabrication methods. This paper aims at examining the recent advancements in 3D bioprinting technology for creating blood vessels, vasculature, and vascularized materials. It provides a comprehensive overview of the progress made and discusses the limitations and challenges faced in current 3D bioprinting of vascularized tissues. In addition, the paper highlights the future research directions focusing on the development of 3D bioprinting techniques and bioinks for creating functional materials.

3D-PRINTED HYBRID SCAFFOLDS FOR CARTILAGE REGENERATION

For chondral damage in younger patients, surgical best practice is microfracture, which involves drilling into the bone to liberate the bone marrow. This leads to a mechanically inferior fibrocartilage formed over the defect as opposed to the desired hyaline cartilage that properly withstands joint loading. While some devices have been developed to aid microfracture and enable its use in larger defects, fibrocartilage is still produced and there is no clear clinical improvement over microfracture alone in the long term. Our goal is to develop 3D printed devices, which surgeons can implant with a minimally invasive technique. The scaffolds should match the functional properties of cartilage and expose endogenous marrow cells to suitable mechanobiological stimuli in-situ, in order to promote healing of articular cartilage lesions before they progress to osteoarthritis, and rapidly restore joint health and mobility. Importantly, scaffolds should direct a physiological host reaction, instead of a foreign body reaction, associated with chronic inflammation and fibrous capsule formation, negatively influencing the regenerative outcome.Our novel silica/polytetrahydrofuran/polycaprolactone hybrids were prepared by sol-gel synthesis and scaffolds were 3D printed by direct ink writing. 3D printed hybrid scaffolds with pore channels of ~250 µm mimic the compressive behaviour of cartilage. Our results show that these scaffolds support human bone marrow stem/stromal cell (hMSC) differentiation towards chondrogenesis in vitro under hypoxic conditions to produce markers integral to articular cartilage-like matrix evaluated by immunostaining and gene expression analysis. Macroscopic and microscopic evaluation of subcutaneously implanted scaffolds in mice showed that scaffolds caused a minimal resolving inflammatory response. Our findings show that 3D printed hybrid scaffolds have the potential to support cartilage regeneration.Acknowledgements: Authors acknowledge funding provided by EPSRC grant EP/N025059/1.

Novel Polycaprolactone‐Chitosan Hybrid Scaffold: A Double‐Sided Hernia Mesh for Regeneration of Abdominal Wall Defects with Minimized Adverse Adhesions

Novel Polycaprolactone‐Chitosan Hybrid Scaffold: A Double‐Sided Hernia Mesh for Regeneration of Abdominal Wall Defects with Minimized Adverse Adhesions

Collagen/polyester-polyurethane porous scaffolds for use in meniscal repair.

Focusing on the regeneration of damaged knee meniscus, we propose a hybrid scaffold made of poly(ester-urethane) (PEU) and collagen that combines suitable mechanical properties with enhanced biological integration. To ensure biocompatibility and degradability, the degradable PEU was prepared from a poly(ε-caprolactone), L-lysine diisocyanate prepolymer (PCL di-NCO) and poly(lactic-co-glycolic acid) diol (PLGA). The resulting PEU (Mn = 52 000 g mol-1) was used to prepare porous scaffolds using the solvent casting (SC)/particle leaching (PL) method at an optimized salt/PEU weight ratio of 5 : 1. The morphology, pore size and porosity of the scaffolds were evaluated by SEM showing interconnected pores with a uniform size of around 170 μm. Mechanical properties were found to be close to those of the human meniscus (Ey ∼ 0.6 MPa at 37 °C). To enhance the biological properties, incorporation of collagen type 1 (Col) was then performed via soaking, injection or forced infiltration. The latter yielded the best results as shown by SEM-EDX and X-ray tomography analyses that confirmed the morphology and highlighted the efficient pore Col-coating with an average of 0.3 wt% Col in the scaffolds. Finally, in vitro L929 cell assays confirmed higher cell proliferation and an improved cellular affinity towards the proposed scaffolds compared to culture plates and a gold standard commercial meniscal implant.

Integrating Melt Electrowriting and Fused Deposition Modeling to Fabricate Hybrid Scaffolds Supportive of Accelerated Bone Regeneration (Adv. Healthcare Mater. 3/2024)

Integrating Melt Electrowriting and Fused Deposition Modeling to Fabricate Hybrid Scaffolds Supportive of Accelerated Bone Regeneration (Adv. Healthcare Mater. 3/2024)

Identification of 1,2,4-triazole-bearing Bis-Schiff base hybrid scaffolds: In vitro and in silico insights to develop promising anti-urease and anti-cancer agents

The present work describes the synthetic procedure of 1,2,4-triazole derivatives (1–14) synthesized efficiently in a single step reaction. Basic skeleton confirmation was achieved through different characterization approaches, such as nuclear magnetic resonance(1HNMR and13CNMR) and high-resolution electron ionization mass spectrometry(HREI-MS). In vitro biological assessment of these scaffolds as anti-urease and anti-cancer agents was analyzed in presence of their standard compounds thiourea (IC50 = 9.30 ± 0.20 µM)and Tetrandrine (IC50 = 11.70 ± 0.10 µM), respectively. Inhibition ranges were observed for all scaffolds with IC50 = 2.10 ± 0.20–––37.40 ± 1.10 µM and IC50 = 4.10 ± 0.10–––39.90 ± 0.20 µM, respectively. Among the screened, the potent behavior were shown by scaffolds 3 (IC50 = 2.10 ± 0.20 and 4.10 ± 0.10 µM), 4(IC50 = 3.20 ± 1.10 and 5.20 ± 0.20 µM), 5(IC50 = 4.20 ± 0.30 and 5.60 ± 0.10 µM), 13(IC50 = 5.80 ± 1.10 and 5.90 ± 0.10 µM)and 14(IC50 = 4.30 ± 1.20 and 6.10 ± 1.20 µM).These analogs show the excellent inhibition owing to the spellbinding reactivity of –CF3, −F, −Cl and –OH moieties, which decelerate enzyme potential via effective binding between drug molecule and enzyme. These compounds were further investigated by means of molecular docking studies which explore the binding interaction of ligand within the binding pockets of enzymes. In this regard, excellent results were found in both the activity profiles of these scaffolds. Additionally, ADMET investigations also strengthen the drug profile of the potent compounds.

Coumarin Chalcone Hybrids: Molecular Hybridization Strategy for Drug Design

Naturally occurring and synthetically produced hybrid compounds are potential reservoir for development of novel drug regimen because of various benefits including effectiveness, minimal side effects, receptor interactions and pharmacokinetic features. Coumarin and chalcone are perfect building blocks for creating hybrid scaffolds that can be used as bioactive agents. These are essential classes of synthetic chemistry with wide range of pharmacological properties. Encouraged by potential therapeutic and medicinal significance of these hybrids, the scientists have reported dozens of coumarin chalcone hybrids with a broad range of biological properties like antioxidant, analgesic, antimicrobial, antiviral, anticancer, antianxiety, antimalarial, anti-inflammatory etc. It is intended to support to medicinal researchers in the efficient, fruitful development of coumarin chalcone hybrids to maximize their biological potential. In view of these findings, we present here some literature review, synthetic methods and pharmacological efficacy, molecular targets.

Development and characterization of antibacterial 3D porous hydroxyapatite-gelatin-PVA scaffolds containing zinc oxide nanoparticles

There is still a need to develop hydroxyapatite (HAp)/gelatin-based porous scaffolds to provide a hybrid system with structural and biochemical properties equivalent to those of bone. Here, we fabricated and characterized 3D hybrid scaffolds composed of HAp nanoparticles synthesized in situ in gelatin and PVA solutions and loaded with combustionally synthesized (10 wt%) zinc oxide nanoparticles (ZnO NPs) to ensure their homogeneous embedding in the polymer matrices. The phase analysis, composition, morphological and microstructural properties of ZnO NPs and freeze-dried hybrid scaffolds were studied. The compressive strength, porosity, swelling capacity, degradation rate, and antibacterial activity of the hybrid scaffolds were measured. The fabricated 3D scaffolds showed high porosity of up to 78 % with a pore size of about 50–300 μm, good mechanical strength in the range of about 55 kPa, high swelling capacity of up to 505 %, and long-term degradation rate of about 22–25 % for up to 35 days. ZnO NPs have a pure phase and a quasi-spherical shape with a size of about 78 ± 25 nm structure and there are no significant differences between the physicochemical properties of ZnO-free scaffolds and ZnO-loaded scaffolds. Incorporation of ZnO NPs into the scaffolds enhanced their antibacterial response against pathogenic Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This work provides advanced 3D porous hybrid bone scaffolds with favorable mechanical performance and antibacterial activity for bone repair and regeneration.

Three Birds, One Stone: An Osteo-Microenvironment Stage-Regulative Scaffold for Bone Defect Repair through Modulating Early Osteo-Immunomodulation, Middle Neovascularization, and Later Osteogenesis.

In order to repair critical-sized bone defects, various polylactic acid-glycolic acid (PLGA)-based hybrid scaffolds are successfully developed as bone substitutes. However, the byproducts of these PLGA-based scaffolds are known to acidify the implanted site, inducing tiresome acidic inflammation. Moreover, these degradation productions cannot offer an osteo-friendly microenvironment at the implanted site, matching natural bone healing. Herein, inspired by bone microenvironment atlas of natural bone-healing process, an osteo-microenvironment stage-regulative scaffold (P80/D10/M10) is fabricated by incorporating self-developed decellularized bone matrix microparticles (DBM-MPs) and multifunctional magnesium hydroxide nanoparticles (MH-NPs) into PLGA with an optimized proportion using low-temperature rapid prototyping (LT-RP) 3D-printing technology. The cell experiments show that this P80/D10/M10 exhibits excellent properties in mechanics, biocompatibility, and biodegradability, meanwhile superior stimulations in osteo-immunomodulation, angiogenesis, and osteogenesis. Additionally, the animal experiments determined that this P80/D10/M10 can offer an osteo-friendly microenvironment in a stage-matched pattern for enhanced bone regeneration, namely, optimization of early inflammation, middle neovascularization, and later bone formation. Furthermore, transcriptomic analysis suggested that the in vivo performance of P80/D10/M10 on bone defect repair is mostly attributed to regulating artery development, bone development, and bone remodeling. Overall, this study reveals that the osteo-microenvironment stage-regulative scaffold provides a promising treatment for bone defect repair.

Preparation and Properties of Antibacterial Silk Fibroin Scaffolds.

The development of a wound dressing with both antibacterial and healing-guiding functions is a major concern in the treatment of open and infected wounds. In this study, poly(hexamethylene biguanide) hydrochloride (PHMB) was loaded into a 3D silk fibroin (SF) scaffold based on electrostatic interactions between PHMB and SF, and PHMB/SF hybrid scaffolds were prepared via freeze-drying. The effects of the PHMB/SF ratio on the antibacterial activity and cytocompatibility of the hybrid scaffold were investigated. The results of an agar disc diffusion test and a bacteriostasis rate examination showed that when the mass ratio of PHMB/SF was greater than 1/100, the scaffold exhibited obvious antibacterial activity against E. coli and S. aureus. L-929 cells were encapsulated in the PHMB/SF scaffolds and cultured in vitro. SEM, laser scanning confocal microscopy, and CCK-8 assay results demonstrated that hybrid scaffolds with a PHMB/SF ratio of less than 2/100 significantly promoted cell adhesion, spreading, and proliferation. In conclusion, a hybrid scaffold with a PHMB/SF ratio of approximately 2/100 not only effectively inhibited bacterial reproduction but also showed good cytocompatibility and is expected to be usable as a functional antibacterial dressing for wound repair.

Reconstruction of tracheal window-shape defect by 3D printed polycaprolatone scaffold coated with Silk Fibroin Methacryloyl.

In this study, we aimed to utilize autologous tracheal epithelia and BMSCs as the seeding cells, utilize PCL coated with SilMA as the hybrid scaffold to carry the cells and KGN, which can selectively stimulate chondrogenic differentiation of BMSCs. This hybrid tracheal substitution was carried out to repair the tracheal partial window-shape defect. Firstly, SilMA with the concentration of 10%, 15% and 20% was prepared, and the experiment of swelling and degradation was performed. With the increase of the concentration, the swelling ratio of SilMA decreased, and the degradation progress slowed down. Upon the result of CCK-8 test and HE staining of 3D co-culture, the SilMA with concentration of 20% was selected. Next, SilMA and the cells attached to SilMA were characterized by SEM. Furthermore, in vitro cytotoxicity test shows that 20% SilMA has good cytocompatibility. The hybrid scaffold was then made by PCL coated with 20% SilMA. The mechanical test shows this hybrid scaffold has better biomechanical properties than native trachea. In vivo tracheal defect repair assays were conducted to evaluate the effect of the hybrid substitution. H&E staining, IHC staining and IF staining showed that this hybrid substitution ensured the viability, proliferation and migration of epithelium. However, it is sad that the results of chondrogenesis were not obvious. This study is expected to provide new strategies for the fields of tracheal replacement therapy needing mechanical properties and epithelization.

Bone regeneration in critical-size defects of the mandible using biomechanically adapted CAD/CAM hybrid scaffolds: An in vivo study in miniature pigs

The study aimed to analyze bone regeneration in critical-size defects using hybrid scaffolds biomechanically adapted to the specific defect and adding the growth factor rhBMP-2.For this animal study, ten minipigs underwent bilateral defects in the corpus mandibulae and were subsequently treated with novel cylindrical hybrid scaffolds. These scaffolds were designed digitally to suit the biomechanical requirements of the mandibular defect, utilizing finite element analysis. The scaffolds comprised zirconium dioxide-tricalcium phosphate (ZrO2-TCP) support struts and TCP foam ceramics. One scaffold in each animal was loaded with rhBMP-2 (100 μg/cm³), while the other served as an unloaded negative control. Fluorescent dyes were administered every 2 weeks, and computed tomography (CT) scans were conducted every 4 weeks. Euthanasia was performed after 3 months, and samples were collected for examination using micro-CT and histological evaluation of both hard and soft tissue.Intravital CT examinations revealed minor changes in radiographic density from 4 to 12 weeks postoperatively. In the group treated with rhBMP-2, radiographic density shifted from 2513 ± 128 (mean ± SD) to 2606 ± 115 Hounsfield units (HU), while the group without rhBMP-2 showed a change from 2430 ± 131 to 2601 ± 67 HU. Prior to implantation, the radiological density of samples measured 1508 ± 30 mg HA/cm³, whereas post-mortem densities were 1346 ± 71 mg HA/cm³ in the rhBMP-2 group and 1282 ± 91 mg HA/cm³ in the control group (p = 0.045), as indicated by micro-CT measurements. The histological assessment demonstrated successful ossification in all specimens. The newly formed bone area proportion was significantly greater in the rhBMP-2 group (48 ± 10%) compared with the control group without rhBMP-2 (42 ± 9%, p = 0.03). The mean area proportion of remaining TCP foam was 23 ± 8% with rhBMP-2 and 24 ± 10% without rhBMP-2.Successful bone regeneration was accomplished by implanting hybrid scaffolds into critical-size mandibular defects. Loading these scaffolds with rhBMP-2 led to enhanced bone regeneration and a uniform distribution of new bone formation within the hybrid scaffolds. Further studies are required to determine the adaptability of hybrid scaffolds for larger and potentially segmental defects in the maxillofacial region.

Integrating Melt Electrowriting and Fused Deposition Modeling to Fabricate Hybrid Scaffolds Supportive of Accelerated Bone Regeneration.

Emerging additive manufacturing (AM) strategies can enable the engineering of hierarchal scaffold structures for guiding tissue regeneration. Here, the advantages of two AM approaches, melt electrowriting (MEW) and fused deposition modelling (FDM), are leveraged and integrated to fabricate hybrid scaffolds for large bone defect healing. MEW is used to fabricate a microfibrous core to guide bone healing, while FDM is used to fabricate a stiff outer shell for mechanical support, with constructs being coated with pro-osteogenic calcium phosphate (CaP) nano-needles. Compared to MEW scaffolds alone, hybrid scaffolds prevent soft tissue collapse into the defect region and support increased vascularization and higher levels of new bone formation 12 weeks post-implantation. In an additional group, hybrid scaffolds are also functionalized with BMP2 via binding to the CaP coating, which further accelerates healing and facilitates the complete bridging of defects after 12 weeks. Histological analyses demonstrate that such scaffolds support the formation of well-defined annular bone, with an open medullary cavity, smooth periosteal surface, and no evidence of abnormal ectopic bone formation. These results demonstrate the potential of integrating different AM approaches for the development of regenerative biomaterials, and in particular, demonstrate the enhanced bone healing outcomes possible with hybrid MEW-FDM constructs.

Development of Self-Assembled Biomimetic Nanoscale Collagen-like Peptide-Based Scaffolds for Tissue Engineering: An In Silico and Laboratory Study.

Development of biocomposite scaffolds has gained tremendous attention due to their potential for tissue regeneration. However, most scaffolds often contain animal-derived collagen that may elicit an immunological response, necessitating the development of new biomaterials. Herein, we developed a new collagen-like peptide,(Pro-Ala-His)10 (PAH)10, and explored its ability to be utilized as a functional biomaterial by incorporating it with a newly synthesized peptide-based self-assembled gel. The gel was prepared by conjugating a pectin derivative, galataric acid, with a pro-angiogenic peptide (LHYQDLLQLQY) and further functionalized with a cortistatin-derived peptide, (Phe-Trp-Lys-Thr)4 (FWKT)4, and the bio-ionic liquid choline acetate. The self-assembly of (PAH)10 and its interactions with the galactarate-peptide conjugates were examined using replica exchange molecular dynamics (REMD) simulations. Results revealed the formation of a multi-layered scaffold, with enhanced stability at higher temperatures. We then synthesized the scaffold and examined its physicochemical properties and its ability to integrate with aortic smooth muscle cells. The scaffold was further utilized as a bioink for bioprinting to form three-dimensional cell-scaffold matrices. Furthermore, the formation of actin filaments and elongated cell morphology was observed. These results indicate that the (PAH)10 hybrid scaffold provides a suitable environment for cell adhesion, proliferation and growth, making it a potentially valuable biomaterial for tissue engineering.

Natural bone inspired core–shell triple-layered gel/PCL/gel 3D printed scaffolds for bone tissue engineering

Despite technological advancements in bone tissue engineering, it is still a challenge to fabricate a scaffold with high bioactivity as well as high mechanical strength that can promote osteogenesis as well as bear load. Here we developed a 3D printed gel-polymer multi-layered hybrid scaffold. The innermost layer is porous gel-based framework made of gelatin/carboxymethyl-chitin/nano-hydroxyapatite and is cryogenically 3D printed. Further, the second and middle layer of micro-engineered polycaprolactone (PCL) is infused in the gel with controlled penetration and tuneable coating thickness. The PCL surface is further coated with a third and final thin layer of gel matrix used for the first layer. This triple-layered structure demonstrates compression strength and modulus of 13.07 ± 1.15 MPa and 21.8 ± 0.82 MPa, respectively, post 8 weeks degradation which is >3000% and >700% than gel scaffold. It also shows degradation of 6.84 ± 0.70% (83% reduction than gel scaffold) after 12 weeks and swelling of 69.09 ± 6.83% (81% reduction) as compared to gel scaffolds. Further, nearly 300%, 250%, 50%, and 440% increase in cellular attachment, proliferation, protein generation, and mineralization, respectively are achieved as compared to only PCL scaffolds. Thus, these hybrid scaffolds offer high mechanical strength, slow degradation rate, high bioactivity, and high osteoconductivity. These multifunctional scaffolds have potential for reconstructing non-load-bearing bone defects like sinus lift, jaw cysts, and moderate load-bearing like reconstructing hard palate, orbital palate, and other craniomaxillofacial bone defects.

A silk fibroin scaffold that accelerates both biodegradation and cell proliferation by incorporating sericin

When 3D silk fibroin scaffolds are used for the regeneration of soft tissues with fast regeneration rates, such as skin dermis, one concern is to accelerate the biodegradation of scaffolds and to match the degradation rate of scaffolds with the regeneration rate of tissues. In this study, sericin was incorporated into 3D silk fibroin scaffolds through crosslinking and followed by freeze-drying. The effects of incorporating sericin on the pore wall microstructure within the scaffolds, the biodegradability of scaffolds and cell proliferation within scaffolds were investigated. It was found that a large number of secondary pores and nanoscale particles were generated on the pore walls within the scaffolds due to the incorporation of sericin and that the number of secondary pores and the size of the particles increased with increasing sericin proportion. The results of in vitro biodegradation and coculture with human umbilical vein vascular endothelial cells demonstrated that the incorporation of sericin not only significantly accelerated the degradation of 3D silk fibroin scaffolds, but also promoted cell adhesion and proliferation. The secondary pores and particles generated on the pore walls inside the fibroin/sericin hybrid scaffolds had a positive contribution to promoting cell adhesion and proliferation. This study provides a biocompatible method for the modification of silk fibroin scaffolds, which can not only accelerate the biodegradation of the scaffold but also promote the adhesion and proliferation of seeded cells.

Fabrication of Gentamicin Sulfate‐Loaded 3D‐Printed Polyvinyl Alcohol/Sodium Alginate/Gelatin‐Methacryloyl Hybrid Scaffolds for Skin Tissue Replacement

Abstract3D‐printed scaffolds can better mimic the function of human skin, both biologically and mechanically. Within the scope of this study, the effect of the addition of different amounts (10, 15, 20 mg) of gentamicin sulfate (GS) to a 10 mL solution of natural and synthetic polymers is investigated. Sodium alginate (SA), gelatin‐methacryloyl (GelMA), and polyvinyl alcohol (PVA) are chosen as bioactive materials. The surface morphology and pore structures are visualized by scanning electron microscopy (SEM). According to the results, it is observed that the pore sizes of all scaffolds are smaller than 270 µm, the lowest value (130 µm) is obtained in the scaffold loaded with 15 mg GS, and it also has the highest tensile strength value (12.5 ± 7.6 MPa). Similarly, it is observed that the tensile strength (9.7 ± 4.5 MPa) is high in scaffold loaded with 20 mg GS. The biocompatibility test is performed with fibroblast cells, and the results show that the scaffolds are biocompatible with cells. The antibacterial test is carried out against the S.aureous and E. coli and the results indicate that all GS‐loaded scaffolds demonstrate antibacterial activity.

Pearl Powder Hybrid Bioactive Scaffolds from Microfluidic 3D Printing for Bone Regeneration.

The development of bioactive scaffolds by mimicking bone tissue extracellular matrix is promising for bone regeneration. Herein, inspired by the bone tissue composition, a novel pearl powder (PP) hybrid fish gelatin methacrylate (GelMa) hydrogel scaffold loaded with vascular endothelial growth factor (VEGF) for bone regeneration is presented. With the help of microfluidic-assisted 3D printing technology, the composition and structure of the hybrid scaffold can be accurately controlled to meet clinical requirements. The combination of fish skin GelMa and PP also endowed the hybrid scaffold with good biocompatibility, cell adhesion, and osteogenic differentiation ability. Moreover, the controlled release of VEGF enables the scaffold to promote angiogenesis. Thus, the bone regeneration in the proposed scaffolds could be accelerated under the synergic effect of osteogenesis and angiogenesis, which has been proved in the rat skull defect model. These features indicate that the PP hybrid scaffolds will be an ideal candidate for bone regeneration in clinical applications.