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Delivery of therapeutic peptides via sublingual administration is extremely desired and 3D printed scaffolds are potential candidates as carriers to enhance insulin delivery. 3D printed sublingual sodium alginate (SA)/polyethylene glycol (PEG) composite scaffolds were produced for enhancing insulin delivery by examining the chemical, morphological, mechanical, thermal, cytotoxic, and pharmacokinetic features. The tensile strength and flexibility of scaffolds increased after loading insulin due to the crystalline structure of insulin. Furthermore, insulin-loaded 9SA/3PEG scaffolds showed ultrafast wetting (<1 s), disintegration (<6 s), and also dissolution (<30 s) according to Hixson-Crowell kinetic model. The cell viability of L929 cells on 3D printed scaffolds was examined and these scaffolds could be safely applied on animals. Pharmacokinetic parameters and blood glucose level were evaluated following sublingual administration of scaffolds to type-1 diabetic rats. A single dose of scaffold presented a longer hypoglycemic effect, reducing ~60% of glycemia after 30 min and it lasted for 12 h by increasing the bioavailability of insulin. Scaffolds indicated a sustained profile for serum insulin levels, which continued to increase slightly after 3 h during the study. The polymeric scaffold with a high safety and efficacy holds a new promising delivery strategy for administering injectable insulin through the sublingual route. [Display omitted] • Sodium alginate/polyethylene glycol scaffolds were produced by 3D printing. • Scaffolds were used as carriers to enhance insulin delivery via sublingual route. • Ultrafast wetting, disintegration (<6 s), and dissolution (<30s) were presented. • Scaffolds show a longer hypoglycemic effect, reducing ~60% of glycemia after 30 min. • Scaffolds indicated a sustained profile for serum insulin levels lasted for 12 h. [ABSTRACT FROM AUTHOR]

Mussel-derived nacre and pearl, which are natural composites composed CaCO3 platelets and interplatelet organic matrix, have recently gained interest due to their osteogenic potential. The crystal form of CaCO3 could be either aragonite or vaterite depending on the characteristics of mineralization template within pearls. So far, little attention has been paid on the different osteogenic capacities between aragonite and vaterite pearl. In the current work, aragonite or vaterite pearl powders were incorporated into poly-l-lactic acid (PLLA) scaffold as bio-functional fillers for enhanced osteogenesis. In intro results revealed that PLLA/aragonite scaffold possessed stronger stimulatory effect on SaOS-2 cell proliferation and differentiation, evidenced by the enhanced cell viability, alkaline phosphatase activity, collagen synthesis and gene expressions of osteogenic markers including osteocalcin, osteopotin and bone sialoprotein. The bone regeneration potential of various scaffolds was evaluated in vivo employing a rabbit critical-sized radial bone defect model. The X-ray and micro-CT results showed that significant bone regeneration and bridging were achieved in defects implanted with composite scaffolds, while less bone formation and non-bridging were found for pure PLLA group. Histological evaluation using Masson's trichrome and hematoxylin/eosin (H&E) staining indicated a typical endochondral bone formation process conducted at defect sites treated with composite scaffolds. Through three-point bending test, the limbs implanted with PLLA/aragonite scaffold were found to bear significantly higher bending load compared to other two groups. Together, it is suggested that aragonite pearl has superior osteogenic capacity over vaterite pearl and PLLA/aragonite scaffold can be employed as a potential bone graft for bone regeneration.

Qinghui Zhao1 12 23 3,* Hongming Tang1 12 23 3,* Lishu Ren4 4, Jie Wei4 4 1School of Life Sciences and Technology, Tongji University, Shanghai 200092, People’s Republic of China; 2Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, People’s Republic of China; 3Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai 200123, People’s Republic of China; 4Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinghui Zhao Tel +86-21-38804518Email qinghui_zhao@126.comPurpose: A bioactive and degradable scaffold of ternary composite with good biocompatibility and osteogenesis was developed for bone tissue repair.Materials and Methods: Polybutylene succinate (PS:50 wt%), magnesium phosphate (MP:40 wt%) and wheat protein (WP:10 wt%) composite (PMWC) scaffold was fabricated, and the biological performances of PMWC were evaluated both in vitro and vivo in this study.Results: PMWC scaffold possessed not only interconnected macropores (400 μm to 600 μm) but also micropores (10 μm ∼ 20 μm) on the walls of macropores. Incorporation of MP into composite improved the apatite mineralization (bioactivity) of PMWC scaffold in simulated body fluid (SBF), and addition of WP into composite further enhanced the degradability of PMWC in PBS compared with the scaffold of PS (50 wt%)/MP (50 wt%) composite (PMC) and PS alone. In addition, the PMWC scaffold containing MP and WP significantly promoted the proliferation and differentiation of mouse pre-osteoblastic cell line (MC3T3-E1) cells. Moreover, the images from synchrotron radiation microcomputed tomography (SRmCT) and histological sections of the in vivo implantation suggested that the PMWC scaffold containing MP and WP prominently improved the new bone formation and ingrowth compared with PMC and PS. Furthermore, the immunohistochemical analysis further confirmed that the PMWC scaffold obviously promoted osteogenesis and vascularization in vivo compared with PMC and PS.Conclusion: This study demonstrated that the biocompatible PMWC scaffold with improved bioactivity and degradability significantly promoted the osteogenesis and vascularization in vivo, which would have a great potential to be applied for bone tissue repair.Keywords: polybutylene succinate, composite scaffold, cytocompatibility, osteogenesis, vascularization

Background/objectives: For treatment of large bone defects challenging in orthopaedic clinics, bone graft substitutes are commonly used for the majority of surgeons. It would be proposed in the current study that our bioactive scaffolds could additionally serve as a local delivery system for therapeutic small molecule agents capable of providing support to enhance biological bone repair. Methods: In this study, composite scaffolds made of poly (lactic-co-glycolic acid) (PLGA) and tricalcium phosphate (TCP) named by P/T was fabricated by a low-temperature rapid prototyping technique. For optimizing the scaffolds, the phytomolecule icaritin (ICT) was incorporated into P/T scaffolds called P/T/ICT. The osteogenic efficacies of the two groups of scaffolds were compared in a successfully established calvarial defect model in rats. Bone regeneration was evaluated by X-ray, micro-computerised tomography (micro-CT), and histology at weeks 4 and/or 8 post-implantation. In vitro induction of osteogenesis and osteoclastogenesis was established for identification of differentiation potentials evoked by icaritin in primary cultured precursor cells. Results: The results of radiographies and decalcified histology demonstrated more area and volume fractions of newly formed bone within bone defect sites implanted with P/T/ICT scaffold than that with P/T scaffold. Undecalcified histological results presented more osteoid and mineralized bone tissues, and also more active bone remodeling in P/T/ICT group than that in P/T group. The results of histological staining in osteoclast-like cells and newly formed vessels indicated favorable biocompatibility, rapid bioresorption and more new vessel growth in P/T/ICT scaffolds in contrast to P/T scaffolds. Based on in vitro induction, the results presented that icaritin could significantly facilitate osteogenic differentiation, while suppressed adipogenic differentiation. Meanwhile, icaritin demonstrated remarkable inhibition of osteoclastogenic differentiation. Conclusion: The finding that P/T/ICT composite scaffold can enhance bone regeneration in calvarial bone defects through facilitating effective bone formation and restraining excessive bone resorption. The translational potential of this article: The osteogenic bioactivity of icaritin facilitated PLGA/TCP/icartin composite scaffold to exert significant bone regeneration in calvarial defects in rat model. It might form an optimized foundation for potential clinical validation in bone defects application.

In the present study, acellular cartilage matrix (ACM) was modified with poly-l-lysine/hyaluronic acid (PLL/HA) multilayers via detergent-enzyme chemical digestion and layer-by-layer self-assembly technology. This modified ACM was then loaded with Transforming Growth Factor Beta 3 (TGF-β3) and incorporated into a thermosensitive hydrogel (TH) to create a HA/PLL-ACM/TH composite scaffold with sustained-release function. This study aimed to evaluate the efficacy of this novel composite scaffold in promoting chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and facilitating osteochondral defect repair. In vitro , isolated, and cultured rat BMSCs were inoculated in equal amounts into TH, ACM/TH, and HA/PLL-ACM/TH groups, with or without TGF-β3 supplementation, for 21 days. Western blot (WB) analysis and immunofluorescence staining were employed to assess the expression levels of collagen II, aggrecan, and SOX-9. In vivo , osteochondral defect was created in the Sprague-Dawley rat trochlea using microdrilling. TH, ACM/TH, and HA/PLL-ACM/TH scaffolds, with or without TGF-β3, were implanted into the defect. After 6 weeks, the repairs were evaluated macroscopically, using Micro computed tomography (micro-CT), histological analysis, and immunohistochemistry. The results demonstrated that the HA/PLL-ACM/TH scaffold loaded with TGF-β3 significantly upregulated the expression of collagen II, aggrecan, and SOX-9 compared with the control and other experimental groups. Furthermore, at 6 weeks postsurgery, the HA/PLL-ACM/TH group loaded with TGF-β3 exhibited superior tissue formation on the joint surface, as confirmed by micro-CT and histological evidence, indicating improved osteochondral repair. These findings suggest that the HA/PLL-ACM/TH scaffold loaded with TGF-β3 holds promise as a therapeutic strategy for osteochondral defect and offers a novel approach for utilizing acellular cartilage microfilaments.

Physical stimulations such as mechanical and electric stimulation can continuously work on bone defect locations to maintain and enhance cell activity, and it has become a hotspot for research in the field of bone repair. Herein, bifunctional porous composite scaffolds with shape memory and piezoelectric functions were fabricated using thermoplastic polyurethane (TPU) and poly(vinylidene fluoride) through triply periodic minimal surfaces design and selective laser sintering technology. Thereinto, the shape fixity ratio and recovery ratio of the composite scaffold reached 98.6% and 81.2%, respectively, showing excellent shape memory functions. More importantly, its piezoelectric coefficient (d33 = 2.47 pC/N) is close to the piezoelectric constant of bone tissue (d33 = 0.7-2.3 pC/N), and the voltage released during the compression process can reach 0.5 V. Furthermore, cyclic compression experiments showed that the strength of composite scaffold was up to 8.3 times compared with the TPU scaffold. Besides, the composite scaffold showed excellent cytocompatibility. In conclusion, the composite scaffold is expected to continuously generate mechanical and electric stimulation due to shape memory and piezoelectric function, respectively, which provide an effective strategy for bone repair.

Repair and regeneration of bone tissue defects is a multidimensional process that has been highly challenging to date. The artificial bone scaffold materials, which play a core role, still face the conflict that a biofriendly porous structure will reduce the mechanical performance and accelerate degradation. Herein, a multistage porous structured hydroxyapatite (HA)/silk fibroin (SF) composite scaffold (e-HA/SF) was successfully constructed by cleverly utilizing electric field-induced gel technology. The results indicated that the prepared e-HA/SF scaffolds possess biomimetic hierarchical porous structures with a suitable porosity similar to that of cancellous bone. The HA nanocrystals were uniformly encapsulated in the three-dimensional space of the composite scaffold, thus endowing the e-HA/SF composite scaffolds with an enhanced mechanical performance. Notably, the maximum compression stress and Young's modulus of e-HA/SF-2 scaffolds can reach 24.66 ± 0.88 and 28.91 ± 3.19 MPa, respectively, which are equivalent to those of cancellous bone. Such mechanical performance enhancement was previously unattainable through conventional freeze-drying strategies. Moreover, the introduction of bioactive nano-HA can trigger the optimal cell response in both static and dynamic cell culture experiments in vitro . The e-HA/SF composite scaffold developed in this study can better balance the conflict between the porous structure and mechanical and degradation properties of porous scaffolds.

In the clinical management of solid tumors, the possibility to successfully couple the regeneration of injured tissues with the elimination of residual tumor cells left after surgery could open doors to new therapeutic strategies. In this work, we present a composite hydrogel–electrospun nanofiber scaffold, showing a modular architecture for the delivery of two pharmaceutics with distinct release profiles, that is potentially suitable for local therapy and post-surgical treatment of solid soft tumors. The composite was obtained by coupling gelatin hydrogels to poly(ethylene oxide)/poly(butylene terephthalate) block copolymer nanofibers. Results of the scaffolds' characterization, together with the analysis of gelatin and drug release kinetics, displayed the possibility to modulate the device architecture to control the release kinetics of the drugs, also providing evidence of their activity. In vitro analyses were also performed using a human epithelioid sarcoma cell line. Furthermore, publicly available expression datasets were interrogated. Confocal imaging showcased the nontoxicity of these devices in vitro. ELISA assays confirmed a modulation of IL-10 inflammation-related cytokine supporting the role of this device in tissue repair. In silico analysis confirmed the role of IL-10 in solid tumors including 262 patients affected by sarcoma as a negative prognostic marker for overall survival. In conclusion, the developed modular composite device may provide a key-enabling technology for the treatment of soft tissue sarcoma. [ABSTRACT FROM AUTHOR]

Hydroxyapatite, a bone mineral was extracted from different seashell species by hydrothermal method and investigated by SEM-EDX, FTIR, TGA, DSC, XRD, and EPR analysis. Amongst, the seashell Dallarca subrostata was chosen for composite preparation by incorporating chitosan and silver nanoparticles which could be used as fillers and films for wound healing applications. Silver ions doped HA were examined using EPR for better biocompatibility. These findings further aim to create a patient-specific implant using 3D modelling. It paves the way for the potential applications as a pre-operative surgical planning procedure and a better point of health care. Further, the biominerals extracted would act as a source for the fabrication of designs and thereafter 3D modelling for investigation. It also rectifies tissue engineering challenges faced so far. [ABSTRACT FROM AUTHOR]

Release kinetics of a drug from the ceramic drug delivery carrier depends on various parameters such as nature of the ceramic, binder, porosity of the ceramics, particle size of the ceramic and, solubility as well as nature of the drug. In the present study effect of formulation on the release kinetics of the drug from hydroxyapatite, the carrier was studied. Hydroxyapatite and Zirconia were taken as ceramic carriers and the model drugs taken for comparison are ciprofloxacin hydrochloride and levofloxacin whereas polyvinyl alcohol was added as a binder. Ciprofloxacin hydrochloride shows a sustained release whereas levofloxacin shows burst release from the ceramic drug carrier. The percentage of polyvinyl alcohol added to the drug played a vital role as a higher concentration of the polymer affects the stability of the drug carrier. Hydroxyapatite/zirconia composite shows sustained release (29%) when compared to pure hydroxyapatite (43%) and zirconia (37%) after 6 hours of immersion in simulated body fluid. Release kinetics shows that the solubility of the drug, concentration of the binder, and the ratio of ceramics in the composites decides the release kinetics of the drug from the drug delivery carrier. [ABSTRACT FROM AUTHOR]

Titanium alloy has been widely used in orthopedic surgeries as bone defect filling. However, the regeneration of high-quality new bones is limited due to the pro-inflammatory microenvironment around implants, resulting in a high occurrence rate of implant loosening or failure in osteological therapy. In this study, extracellular matrix-mimetic polysaccharide hydrogel co-delivering BMP-2 and interleukin (IL)-4 was composited with 3D printed titanium alloy to promote the osseointegration and regulate macrophage response to create a pro-healing microenvironment in bone defect. Notably, it is discovered from the bioinformatics data that IL-4 and BMP-2 could affect each other through multiple signal pathways to achieve a synergistic effect toward osteogenesis. The composite scaffold significantly promoted the osteoblast differentiation and proliferation of human bone marrow mesenchyme stem cells (hBMSCs). The repair of large-scale femur defect in rat indicated that the dual-cytokine-delivered composite scaffold could manipulate a lower inflammatory level in situ by polarizing macrophages to M2 phenotype, resulting in superior efficacy of mature new bone regeneration over the treatment of native titanium alloy or that with an individual cytokine. Collectively, this work highlights the importance of M2-type macrophages-enriched immune-environment in bone healing. The biomimetic hydrogel–metal implant composite is a versatile and advanced scaffold for accelerating in vivo bone regeneration, holding great promise in treating orthopedic diseases. [ABSTRACT FROM AUTHOR]

In this study, we investigated the effect of three-dimensional of naringin/gelatin microspheres/nano-hydroxyapatite/silk fibroin (NG/GMs/nHA/SF) scaffolds on repair of a critical-size bone defect of lumbar 6 in osteoporotic rats. In this work, a cell-free scaffold for bone-tissue engineering based on a silk fibroin (SF)/nano-hydroxyapatite (nHA) scaffold was developed. The scaffold was fabricated by lyophilization. Naringin (NG) was loaded into gelatin microspheres (GMs), which were encapsulated in the nHA/SF scaffolds. The materials were characterized using x ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis. Moreover, the biomechanics, degradation, and drug-release profile of the scaffold were also evaluated. In vitro , the effect of the scaffold on the adhesion, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) was evaluated. In vivo , at 3 months after ovariectomy, a critical-size lumbar defect was indued in the rats to evaluate scaffold therapeutic potential. A 3-mm defect in L6 developed in 60 SD rats, which were randomly divided into SF scaffold, nHA/SF scaffold, NG/nHA/SF scaffold, NG/GMs/nHA/SF scaffold, and blank groups (n = 12 each). At 4, 8, 12, and 16 weeks postoperatively, osteogenesis was evaluated by X-ray, micro-computed tomography, hematoxylin-eosin staining, and fast green staining, and by analysis of BMP-2, Runx2, and Ocn protein levels at 16 weeks. In our results, NG/GM/nHA/SF scaffolds exhibited good biocompatibility, biomechanical strength, and promoted BMSC adhesion, proliferation, and calcium nodule formation in vitro. Moreover, NG/GMs/nHA/SF scaffolds showed greater osteogenic differentiation potential than the other scaffolds in vitro. In vivo , gradual new bone formation was observed, and bone defects recovered by 16 weeks in the experimental group. In the blank group, limited bone formation was observed, and the bone defect was obvious. In conclusion, NG/GMs/nHA/SF scaffolds promoted repair of a lumbar 6 defect in osteoporotic rats. Therefore, the NG/GMs/nHA/SF biocomposite scaffold has potential as a bone-defect-filling biomaterial for bone regeneration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Some studies have shown that basic fibroblast growth factor can promote the proliferation and osteogenic differentiation of mesenchymal stem cells. OBJECTIVE: To compare the ability of acellular bone matrix/chitosan scaffold combined with basic fibroblast growth factor in repairing rabbit femoral defect. METHODS: The acellular bone matrix/chitosan scaffolds were prepared by fusion blending and freeze-drying method, and the acellular bone matrix/chitosan scaffold loaded with basic fibroblast growth factor was prepared by immersion method. Mouse embryonic osteoblasts MC3T3-E1 were seeded on the surface of the two scaffolds for cell proliferation, cell adhesion and osteogenic gene detection. Cells cultured alone served as control. Bone defect models with a diameter of 5 mm were made in bilateral distal femurs using thirty-six 6-month-old New Zealand white rabbits and randomly divided into three groups by drawing lots. The blank group was not intervened. The simple composite scaffold and growth factor + composite scaffold groups were implanted with acellular bone matrix/chitosan scaffold and acellular bone matrix/chitosan scaffold loaded with basic fibroblast growth factor for X-ray and histological examination. RESULTS AND CONCLUSION: (1) Within 1-11 days of culture, the cell proliferation of basic fibroblast growth factor/acellular bone matrix/chitosan scaffold group was faster than that of the acellular bone matrix/chitosan scaffold group (P < 0.05), and that of the acellular bone matrix/chitosan scaffold group was faster than that of the control group (P < 0.05). (2) After 4 days of co-culture with the scaffold, the mRNA expressions of type I collagen, osteocalcin, osteopontin and Runx2 were higher in the cells in basic fibroblast growth factor/acellular bone matrix/chitosan scaffold group cultured for 4 and 7 days than those of acellular bone matrix/chitosan scaffold group (P < 0.05), and the mRNA expression of alkaline phosphatase was higher than that of acellular bone matrix/chitosan scaffold group after 7 days of culture (P < 0.05). (3) Scanning electron microscopy showed that the scaffolds of the two groups supported the adhesion of MC3T3-E1 cells after 7 days of co-culture. (4) X-ray film of animal experiment showed that there was no obvious bone repair in the blank group at 12 weeks after operation; new bone formation could be seen at 8 weeks after operation in the simple composite scaffold group, and obvious new bone formation could be seen at 12 weeks after operation; new bone formation could be seen at 4 weeks after operation in the cytokine + composite scaffold group, and the bone defect site was almost completely repaired at 12 weeks after operation (5) Hematoxylin staining and Masson staining showed that a large amount of fibrous tissue could be seen in the blank group at 12 weeks after operation; a large amount of new bone formation could be seen in the two scaffold groups, in which the area and maturity of new bone formation in the growth factor + composite scaffold group were higher than those in the simple composite scaffold group. (6) The results showed that the acellular bone matrix/chitosan composite scaffold loaded with basic fibroblast growth factor is an ideal bone tissue repair material, which can promote bone formation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ti6Al4V powder was surface modified by NaOH treatment to form uniform nano network. • Sodium ions were replaced by calcium ions in the network by ion exchange method. • Presence of Ca and Ag transformed the network into anatase and calcium titanate. • Surface modified Ti6Al4V showed good antibacterial activity and biocompatibility. • Composite scaffolds were prepared by blending surface modified Ti6Al4V with PMMA. The present work describes a technique to develop silver nanoparticles decorated calcium titanate–titania (AgNPs-CT-TiO 2) nanostructured layer over Ti6Al4V alloy powder by simple chemical and heat treatment approach. The NaOH solution and heat treatment form a uniform porous nano-network morphology of sodium titanate and subsequent calcium nitrate treatment transforms it into calcium titanate along with rutile TiO 2. However, simultaneous treatment with calcium and silver nitrate solution allows the incorporation of both calcium and silver ions over the nano-network morphology leading to the formation of AgNPs decorated calcium titanate along with anatase TiO 2 (AgNPs-CT-TiO 2 @Ti6Al4V) that collectively induces biocompatibility towards MG 63 osteoblast-like cells as well as antimicrobial activity against Staphylococcus aureus. Thus modified AgNPs-CT-TiO 2 @Ti6Al4V alloy powders were subsequently blended with polymethyl methacrylate to develop a composite scaffold using NaCl as a porogen. This composite could be used as a scaffold or bone cement in various bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

Animal derived biomaterials have attracted much attentions in treating large size bone defect due to their excellent biocompatibility and potent bioactivities offered by the biomacromolecules and growth factors contained in these materials. Dermis-derived matrix (ADM) has been used as skin grafts and wound dressings for decades, however its application in bone tissue engineering has been largely limited as ADM possesses a dense structure which does not support bone tissue ingrowth. Recently, we have successfully fabricated porous scaffold structure using an ADM with the aid of micronization technique. When integrated with inorganic components such as calcium phosphate, ADM could be transformed to bone graft substitutes with desirable osteogenic properties. While purified and chemically cross-linked collagen has lost its natural structure, our ADM successfully preserved natural tropocollagen structure, as well as other bioactive components. A composite scaffold was fabricated by incorporating dicalcium phosphate (DCP) microparticles into ADM microfibers and freeze-dried to form a highly porous structure. Unlike conventional ADM materials, this scaffold possesses high porosity with interconnected pores. More importantly, our evaluation data demonstrated that it performed much more effective in treating critical bone defects in comparison with best commercial product on the market. In a head-to-head comparison with a commercial bone graft material Bongold®, the ADM/DCP scaffold showed superior osteogenic capacity by filling the defect with well-organized new bone tissue in a rabbit radius segmental defect model. Put together, our results exhibited a novel bone graft substitute was developed by circumventing processing barriers associated with natural ADM, which offers another novel bone graft substitute for bone regeneration. [ABSTRACT FROM AUTHOR]

Yi-Hsun Yu,1,2 Demei Lee,2 Yung-Heng Hsu,1,2 Ying-Chao Chou,1,2 Steve WN Ueng,1 Che-Kang Chen,2 Shih-Jung Liu1,2 1Department of Orthopedic Surgery, Musculoskeletal Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Taoyuan, TaiwanCorrespondence: Shih-Jung LiuBiomaterials Lab, Department of Mechanical Engineering, Chang Gung University, No. 259 Wen-Hwa 1st Road, Guishan District, Taoyuan 333, TaiwanTel +886 3 211 8166Fax +886 3 211 8558Email shihjung@mail.cgu.edu.twIntroduction: Masquelet proposed a new solution for the healing of segmental bone defects, thus minimizing the disadvantages associated with traditional bone grafting. However, a major factor leading to the failure of this technique pertains to be the residual infection. Accordingly, we developed an antibiotic- and osteo-inductive agent-loaded composite scaffold to solve this problem.Methods: A mesh-like polycaprolactone scaffold was prepared using a lab-exploited solution-type three-dimensional printer, and hybrid sheath-core structured poly(lactic-co-glycolic-acid) nanofibers were fabricated using co-axial electrospinning technology. Vancomycin, ceftazidime, and bone morphological protein (BMP)-2 were employed. The in vitro and in vivo (rabbit fracture model) release patterns of applied agents from the composite scaffold were investigated.Results: The results revealed that the drug-eluting composite scaffold enabled the sustainable release of the medications for at least 30 days in vitro. Animal tests demonstrated that a high concentration of medications was maintained. Abundant growth factors were induced within the bioactive membrane stimulated by the applied scaffold. Finally, satisfactory bone healing potential was observed on radiological examination and biomechanical evaluation.Discussion: The developed composite scaffold may facilitate bone healing by inducing bioactive membrane formation and yielding high concentrations of antibiotics and BMP-2 during the Masquelet procedure.Keywords: Masquelet procedure, composite scaffold, three-dimensional printing, co-axial electrospinning

Nowadays, the development of drug-loaded electrospun organic-inorganic composite scaffolds for tissue engineering application is an attractive approach. In this study, a composite scaffold of Poly-l-lactic acid (PLLA) incorporated dexamethasone (Dexa) loaded Mesoporous Silica Nanoparticles (MSN) coated with Chitosan (CS) were fabricated by electrospinning for bone tissue engineering application. The MSN was prepared by precipitation method. After that, Dexamethasone (Dexa) was loaded into MSNs (MSN-Dexa). In the following, CS was coated over the prepared nanoparticles to form MSN-Dexa@CS and then, were mixed to PLLA solution to form MSN-Dexa@CS/PLLA composite for electrospinning. The surface morphology, hydrophilicity, tensile strength and the bioactivity of the scaffolds were characterized. The osteogenic proliferation and differentiation potential were evaluated by MTT assay and by measuring the basic osteogenic markers: the activity of the enzyme alkaline phosphatase and the level of calcium deposition. The composite scaffolds prepared here have conductive surface property and have a better osteogenic potential than pure PLLA scaffolds. Hence, the controlled release of nanoparticle containing Dexa from composite scaffold supported the osteogenesis and made the composite scaffolds ideal candidates for bone tissue engineering application and pH-sensitive delivery of drugs at the site of implantation in tissue regeneration.

In recent years, 3D printing has gradually become a well-known new topic and a research hotspot. At the same time, the advent of 3D printing is inseparable from the preparation of bio-ink. Natural materials have the advantages of low toxicity or even non-toxicity, there being abundant raw materials, easy processing and modification, excellent mechanical properties, good biocompatibility, and high cell activity, making them very suitable for the preparation of bio-ink. With the help of 3D printing technology, the prepared materials and scaffolds can be widely used in tissue engineering and other fields. Firstly, we introduce the natural materials and their properties for 3D printing and summarize the physical and chemical properties of these natural materials and their applications in tissue engineering after modification. Secondly, we discuss the modification methods used for 3D printing materials, including physical, chemical, and protein self-assembly methods. We also discuss the method of 3D printing. Then, we summarize the application of natural materials for 3D printing in tissue engineering, skin tissue, cartilage tissue, bone tissue, and vascular tissue. Finally, we also express some views on the research and application of these natural materials.

In this study, composite scaffolds based on poly(caprolactone) (PCL) and non‐covalently functionalized few‐layer graphene (FLG) were manufactured by an extrusion‐based system for the first time. For that, functionalized FLG powder was obtained through the evaporation of a functionalized FLG aqueous suspension prepared from a graphite precursor. Cryomilling was shown to be an efficient mixing method, producing a homogeneous dispersion of FLG particles onto the PCL polymeric matrix. Thereafter, fused deposition modeling (FDM) was used to print 3D scaffolds and their morphology, thermal, biodegradability, mechanical, and cytotoxicity properties were analysed. The presence of functionalized FLG demonstrated to induce slight changes in the microstructure of the scaffold, did not affect the thermal stability and enhanced significantly the compressive modulus. The composite scaffolds presented a porosity of around 40% and a mean pore size in the range of 300 μm. The cell viability and proliferation of SaOs‐2 cells were assessed and the results showed good cell viability and long‐term proliferation onto produced composite scaffolds. Therefore, these new FLG/PCL scaffolds comprised adequate morphological, thermal, mechanical, and biological properties to be used in bone tissue regeneration. [ABSTRACT FROM AUTHOR]

The bone healing defects resulting from bone disease remain a significant clinical challenge. The bone tissue engineering scaffolds combined with osteoinductive compounds represent an effective approach to overcome this challenge. In this study, a novel chitosan-based scaffold was prepared by incorporating modified natural diatomite (DE) as filler and adsorption element. Specifically, modified-diatomite (MDE) was synthesized by grafting polyethyleneimine (PEI) on the surface of diatomite via hydroxyl groups. The physicochemical characteristics of MDE, including chemical composition, zeta potential, and adsorption behavior, were investigated successively. Further, the mechanical strength, drug release, cytotoxicity and osteogenic activity analyses were carried out for the scaffold material. The FTIR and zeta potential analyses exhibited that the amino groups (–NH2) were grafted on MDE, and the surface potential of diatomite altered from −24 mV to 55 mV. Subsequently, the protein adsorption capacity and cytocompatibility of MDE were observed to be improved as compared to DE. The compressive strength was observed to be enhanced due to the addition of MDE. Besides, the composite scaffold loaded with rhBMP-2 demonstrated a more positive impact on proliferation and osteogenic differentiation of the bone mesenchymal stem cells, thus, indicating an optimal bone regeneration capacity. The findings obtained in this study reveal that the MDE-rhBMP-2/CS composite scaffold can be potentially used to promote the bone tissue regeneration. [ABSTRACT FROM AUTHOR]

In the present study, mechanical and chemical properties of the bioglass-ceramic/gelatin composite scaffolds were investigated. The reinforcing particles were synthesized using the sol-gel method in SiO 2 –CaO–P 2 O 5 systems. The composite scaffolds were also fabricated through solvent casting and freeze-drying routes. The effect of the chemical composition of the synthesized particles and temperature of the heat treatment process on the mechanical and chemical properties of the bioglass containing scaffolds were investigated in detail. Two different coverages, namely gelatin-glutaraldehyde and silica, were utilized for covering the composite scaffolds. According to the X-ray diffraction results, heat-treating the particles at 1100 °C caused the crystallization of the Ca 3 (PO 4) 2 phase. Based on the three-point flexural test results, the final mechanical strength of the gelatin-glutaraldehyde-covered scaffolds ranged between 2 and 4 MPa. Covering the composite scaffolds with the silica coverage remarkably increased the final strength values ranging between 12 and 18 MPa. The in vitro cell-based experiment results indicate the cytocompatibility of the scaffolds when they are incubated with dental pulp stem cells. Also, the presence of the silica coverage on the scaffolds increased the viability of the stem cells in comparison with the gelatin-glutaraldehyde-covered scaffolds. Furthermore, evaluation of the bioactivity behavior of the scaffolds showed that the Ca 2 SiO 4 phase was formed on the surface of the samples from 7 to 21 days of immersion in simulated body fluid (SBF). The morphology of the mineralized phase on the surface of the scaffolds changed from Cauliflower to rod-like nodules by changing the type of scaffold coverage from gelatin-glutaraldehyde to silica after immersion in SBF media. Altogether, the bioglass-ceramic/gelatin composite scaffolds could have a promising role in bone tissue engineering application. [Display omitted] • Using a silica coverage highly improved the flexural strength of the scaffolds. • The silica coverage improved the viability of dental pulp stem cells on the scaffolds. • Heat treating the particles at 1100 °C increased the flexural strength of the scaffolds. • Ca2SiO4 phase was crystallized on the scaffolds during immersion in SBF media. • Different scaffold coverages changed the morphology of the mineralized phase in SBF. [ABSTRACT FROM AUTHOR]

Biodegradable materials have been received great attention as bone graft substitutes for bone regeneration and tissue engineering. However, their low mechanical property remains a major challenge for the use in load-bearing applications. Here, we developed mechanically reinforced composite scaffold containing adhesive levan as a binder for sintered hydroxyapatite (sHAp) and then examined the mechanical and thermal properties of the composite scaffold. We found that sHAp-levan composite scaffold exhibited remarkably enhanced mechanical strength, which is similar to that of polymethyl methacrylate (PMMA) bone cement. This composite scaffold can be utilized as a promising bone graft for bone regeneration and tissue engineering. [ABSTRACT FROM AUTHOR]

Irreversible bone defects resulting from trauma, infection, and degenerative illnesses have emerged as a significant health concern. Structurally and functionally controllable hydrogels made by bone tissue engineering (BTE) have become promising biomaterials. Natural proteins are able to establish connections with autologous proteins through unique biologically active regions. Hydrogels based on proteins can simulate the bone microenvironment and regulate the biological behavior of stem cells in the tissue niche, making them candidates for research related to bone regeneration. This article reviews the biological functions of various natural macromolecular proteins (such as collagen, gelatin, fibrin, and silk fibroin) and highlights their special advantages as hydrogels. Then the latest research trends on cross-linking modified macromolecular protein hydrogels with improved mechanical properties and composite hydrogels loaded with exogenous micromolecular proteins have been discussed. Finally, the applications of protein hydrogels, such as 3D printed hydrogels, microspheres, and injectable hydrogels, were introduced, aiming to provide a reference for the repair of clinical bone defects.

The utilization of micronano composite scaffolds has been extensively demonstrated to confer the superior advantages in bone repair compared to single nano- or micron-sized scaffolds. Nevertheless, the enhancement of bioactivities within these composite scaffolds remains challenging. In this study, we propose a novel approach to combine melt electrowriting (MEW) and solution electrospinning (SES) techniques for the fabrication of a composite scaffold incorporating hydroxyapatite (HAP), an osteogenic component, and roxithromycin (ROX), an antibacterial active component. Scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) confirmed the hierarchical architecture of the nanofiber-microgrid within the scaffold, as well as the successful loading of HAP and ROX. The incorporation of HAP enhanced the water absorption capacity of the composite scaffold, thus promoting cell adhesion and proliferation, as well as osteogenic differentiation. Furthermore, ROX resulted in effective antibacterial capability without any observable cytotoxicity. Finally, the scaffolds were applied to a rat calvarial defect model, and the results demonstrated that the 20% HAP group exhibited superior new bone formation without causing adverse reactions. Therefore, our findings present a promising strategy for designing and fabricating bioactive scaffolds for bone regeneration.

The innate immune response is crucial to inflammation, but how neutrophils and macrophages act in bone repair and tissue engineering treatment strategies await clarification. In this study, it is found that N2 neutrophils release stronger "eat me" signals to induce macrophage phagocytosis and polarize into the M2 anti-inflammatory phenotype. Guided by this biological mechanism, a mesoporous bioactive glass scaffold (MBG) is filled with hyaluronic acid methacryloyl (HAMA) hydrogel loaded with Transforming growth factor-β1 (TGFβ1) adenovirus (Ad@H), constructing a genetically engineered composite scaffold (Ad@H/M). The scaffold not only has good hydrophilicity and biocompatibility, but also provides mechanical stress support for bone repair. Adenovirus infection quickly induces N2 neutrophils, upregulating NF-κB and MAPK signaling pathways through Toll-like receptor 4 (TLR4) to promote the inflammatory response and macrophage phagocytosis. Macrophages perform phagocytosis and polarize towards the M2 phenotype, mediating the inflammatory response by inhibiting the PI3K-AKT-NF-κB pathway, maintaining homeostasis of the osteogenic microenvironment. The role of the Ad@H/M scaffold in regulating early inflammation and promoting long-term bone regeneration is further validated in vivo. In brief, this study focuses on the cascade of reactions between neutrophils and macrophage subtypes, and reports a composite scaffold that coordinates the innate immune response to promote bone repair., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Bone scaffolds play an important role in promoting the healing of large bone defects. However, the type of scaffold material, type of drug loaded into the scaffold, and method of preparation have a significant impact on the scaffold's properties. In this study, we developed a composite scaffold comprising sodium alginate (SA), chitosan (CS), and hydroxyapatite (HA). The composite stent carries vascular endothelial growth factor (VEGF), wrapped in internal microspheres, and vancomycin (VAN). The microspheres are wrapped in an outer matrix formed by SA, CS, and HA, whereas the outer matrix carries VAN. Using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction, and scanning electron microscopy analyses, we studied the contraction rate, swelling, porosity, mechanical properties, degradation, and drug release ability of all the composite scaffolds. The best scaffold, as demonstrated by the results of these studies, was the HA6(SA/CS)4@VAN/VEGF scaffold. The antibacterial ability of the HA6(SA/CS)4@VAN/VEGF scaffold was determined using Staphylococcus aureus (S. aureus). Cytotoxicity, cell adhesion, and osteogenic properties of the HA6(SA/CS)4@VAN/VEGF scaffold were studied using bone marrow mesenchymal stem cells. The results indicate that the HA6(SA/CS)4@VAN/VEGF scaffold exhibits good physical, chemical, antibacterial, and osteogenic properties, and is, thus, a new type of bone scaffold composite material with good osteogenic potential.

Recruiting periapical stem cells into the root canal and inducing their odontogenic differentiation are both vital for pulp regeneration. This study was aimed at developing a kind of bioactive composite scaffolds (G/PSC scaffolds) by combining the pH-neutral bioactive glass named PSC and gelatin. The incorporation of PSC endowed the scaffolds with bioactivity and enhanced its resistance to enzymatic hydrolysis in vitro while maintaining its high water absorption capacity. The G/PSC scaffold with a PSC content of 0.5 mg/mL in 3% gelatin solution showed the best overall performance, released large amounts of silicate ions and maintained a neutral pH after soaking in simulated body fluid (SBF). Human bone marrow mesenchymal stem cells (hBMMSCs) developed good cell morphology with affluent pseudopods on the G/PSC scaffold and infiltrated fairly deep into it. Additionally, hBMMSCs showed increased proliferation and mRNA expression levels of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP-1), alkaline phosphatase (ALP), collagen type I (Col-I), osteocalcin (OCN), and runt-related transcription factor 2 (Runx2). The present results demonstrated that the G/PSC scaffold significantly promoted hBMMSC chemotaxis, proliferation and odontogenic differentiation. Therefore, the G/PSC scaffold is a promising material for pulp regeneration.

Repair of articular cartilage defects is a challenging aspect of clinical treatment. Kartogenin (KGN), a small molecular compound, can induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. Here, we constructed a scaffold based on chondrocyte extracellular matrix (CECM) and poly(lactic-co-glycolic acid) (PLGA) microspheres (MP), which can slowly release KGN, thus enhancing its efficiency. Cell adhesion, live/dead staining, and CCK-8 results indicated that the PLGA(KGN)/CECM scaffold exhibited good biocompatibility. Histological staining and quantitative analysis demonstrated the ability of the PLGA(KGN)/CECM composite scaffold to promote the differentiation of BMSCs. Macroscopic observations, histological tests, and specific marker analysis showed that the regenerated tissues possessed characteristics similar to those of normal hyaline cartilage in a rabbit model. Use of the PLGA(KGN)/CECM scaffold may mimic the regenerative microenvironment, thereby promoting chondrogenic differentiation of BMSCs in vitro and in vivo. Therefore, this innovative composite scaffold may represent a promising approach for acellular cartilage tissue engineering.

Exploration for ideal bone regeneration materials still remains a hot research topic due to the unmet clinical challenge of large bone defect healing. Bone grafting materials have gradually evolved from single component to multiple-component composite, but their functions during bone healing still only regulate one or two biological processes. Therefore, there is an urgent need to develop novel materials with more complex composition, which convey multiple biological functions during bone regeneration. Here, we report an naturally nanostructured ECM based composite scaffold derived from fish air bladder and combined with dicalcium phosphate (DCP) microparticles to form a new type of bone grafting material. The DCP/acellular tissue matrix (DCP/ATM) scaffold demonstrated porous structure with porosity over 65% and great capability of absorbing water and other biologics. In vitro cell culture study showed that DCP/ATM scaffold could better support osteoblast proliferation and differentiation in comparison with DCP/ADC made from acid extracted fish collagen. Moreover, DCP/ATM also demonstrated more potent bone regenerative properties in a rat calvarial defect model, indicating incorporation of ECM based matrix in the scaffolds could better support bone formation. Taken together, this study demonstrates a new avenue toward the development of new type of bone regeneration biomaterial utilizing ECM as its key components.

The application of multilayered monolithic scaffolds to repair osteochondral defects has become a hot research topic due to the advantage of simulating native osteochondral physiological structure. However, it was difficult to promote proliferation and migration of different kinds of cells in the corresponding layers under the same culture condition. Besides, the methods utilized in previous researches to construct tissue-engineered osteochondral construct were time-consuming, laborious, complicated, costly and difficult to ensure the quality and integration of multilayered construction. Inspired by the application of titanium mesh cage (TMC) for bone graft in spinal fusion surgery, we attempt to 3D print an integrated tri-layered scaffold with Titanium-Mesh-Cage base which could be filled with autogenous cancellous bone for bone graft to the osteochondral defect. Finally, the results of repairing cartilage defects of knee with this scaffold in goat model were evaluated. The results of in-vivo experiments suggested that utilizing the integrated tri-layered scaffold with Titanium-Mesh-Cage base to repair osteochondral defect was a convenient, cost-effective and time-saving procedures, which could achieve a satisfactory repair result as good as that of Mosaicplasty.

The combination of biomimetic and 3D printing has created novel opportunities for the manufacture of 3D engineered materials. A sub-microscale E -Jet 3D printing method, inspired by the dehydration and protein enrichment process of silkworm, was developed to fabricate composite bone tissue scaffold with the characteristics of controllability, fast and inexpensive. By applying the resultant effects of thermal field and flow field to low viscous composite ink, the concentration gradient biopolymer ink was obtained near the needle tip, mimicking the advanced dehydration of natural spinning apparatus. After electrical shearing force were applied on concentration gradient ink, a stable and fine jet formed. Various printing modes (droplet, continuous fiber) and structure resolutions were achieved by adjusting local solvent evaporation. Thin film, high resolution 2D structures, high aspect ratio well-bonding 3D structures were fabricated. The printed result showed that a 100 μm-sized needle could be employed directly to print patterning down to 800 nm. The printed composite scaffold with controllability of fiber size and space has been proved the feasibility as a medium for bone tissue regeneration. It can be estimated that the novel biomimetic E -Jet 3D printing technique is a new and promising way for bone tissue repairing. Unlabelled Image • A biomimetic sub-microscale E -Jet 3D printing method was developed. • Concentration gradient biopolymer ink was obtained near a microscale needle tip. • Various complex structures were directly printed at a resolution of 800 nm. • The printed 3D scaffold with ordered cell scale fibers could be employed for bone tissue repairing. [ABSTRACT FROM AUTHOR]

There has been an increase in the incidence of hypopharyngeal and cervical esophageal cancer worldwide, and hence growing needs for hypopharyngeal and cervical esophageal tissue repair. This work produced a bi-layer composite scaffold with decellularized small intestine submucosa and polylactic-co-glycolic acid, which resembled the layered architectures of its intended tissues. The decellularized small intestine submucosa contained minimal residual DNA (52.5 ± 1.2 ng/mg) and the composite scaffold exhibited satisfactory mechanical properties (a tensile modulus of 21.1 ± 4.8 MPa, an ultimate tensile strength of 14.0 ± 2.9 MPa and a failure strain of 26.9 ± 5.1%). The interactions between cells and the respective layers of the scaffold were characterized by CCK-8 assays, immunostaining and Western blotting. Desirable cell proliferation and phenotypic behaviors were observed. These results have provided an important basis for the next-step in vivo studies of the scaffold, and bode well for its future clinical applications. [ABSTRACT FROM AUTHOR]

Melt electrowriting (MEW) can print high-resolution scaffolds with the ultrafine fibers from 800 nm to 20 µm. However, the cell seeding efficiency relatively low due to the large pore size of the MEW scaffold. Here, we reported a method to solve this dilemma by electrospinning a gelatin methacrylate (GelMA) hydrogel fibers membrane (HFM) on the MEW scaffold. This composite scaffold can own the controlled structures and porosity and excellent cell seeding performance. We systematically investigate the fabrication, morphology, and biocompatibility of composite scaffolds. The implanting of human umbilical vein endothelial cells(HUVES) showed excellent adhesion and biocompatibility on the composite scaffold. Moreover, the cells migrated gradually into the MEW scaffold along the GelMA HFM to form the cell sheet. We hold the opinion that the composite scaffolds have potential applications in the field of tissue engineering repair. [ABSTRACT FROM AUTHOR]

Artificial bioactive materials have received increasing attention worldwide in clinical orthopedics to repair bone defects that are caused by trauma, infections or tumors, especially dedicated to the multifunctional composite effect of materials. In this study, a weakly alkaline, biomimetic and osteogenic, three-dimensional composite scaffold (3DS) with hydroxyapatite (HAp) and nano magnesium oxide (MgO) embedded in fiber (F) of silkworm cocoon and silk fibroin (SF) is evaluated comprehensively for its bone repair potential in vivo and in vitro experiments, particularly focusing on the combined effect between HAp and MgO. Magnesium ions (Mg2+) has long been proven to promote bone tissue regeneration, and HAp is provided with osteoconductive properties. Interestingly, the weak alkaline microenvironment from MgO may also be crucial to promote Sprague-Dawley (SD) rat bone mesenchymal stem cells (BMSCs) proliferation, osteogenic differentiation and alkaline phosphatase (ALP) activities. This SF/F/HAp/nano MgO (SFFHM) 3DS with superior biocompatibility and biodegradability has better mechanical properties, BMSCs proliferation ability, osteogenic activity and differentiation potential compared with the scaffolds adding HAp or MgO alone or neither. Similarly, corresponding meaningful results are also demonstrated in a model of distal lateral femoral defect in SD rat. Therefore, we provide a promising 3D composite scaffold for promoting bone regeneration applications in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Human adipose‐derived stem/stromal cells (hASCs) have been popularly studied as cell‐based therapy in the field of regenerative medicine due to their ability to differentiate into several cell types. In this study, in order to improve the mechanical strength and bioactivity of scaffolds for bone tissue engineering, three types of mesoporous bioactive glasses with different shapes and compositions were dispersed in the silk fibroin/chitosan (SF/CS)‐based scaffolds, which were fabricated with a combination of freezing and lyophilization. The characteristic and physical properties of these composite scaffolds were evaluated. The biocompatibility was also assessed through hASCs in vitro tests. Both Alamar Blue® and Live/Dead assay® revealed that the spherical mesoporous bioactive glass doped scaffolds enhanced cell viability and proliferation. Furthermore, the addition of spherical mesoporous bioactive glass into SF/CS scaffolds encouraged hASC osteogenic differentiation as well. These results suggested that this composite scaffold can be applicable material for bone regeneration. [ABSTRACT FROM AUTHOR]

Over the years, considerable improvements have been made for the repair of cartilage lesions in the field of cartilage tissue engineering. Constructing scaffolds with close similarity to niches regarding biochemical composition and mechanical characteristics with the best efficiency is a great challenge for scientists and researchers in this field. On the other hand, natural polymers such as hyaluronic acid are difficult to be used in scaffolds construction due to some problems arising from their physicochemical properties such as poor mechanical strength. In this study, to overcome this problem a new nanofibrous composite scaffold was constructed using one of the derivatives of hyaluronic acid, benzyl hyaluronate (BH), in combination with Polyethersulfone (PES) and its chondroinductivity potential was measured using human adipose derived mesenchymal stem cells (hADSCs). Scanning electron microscopy (SEM) and tensile tests were performed to evaluate the characteristics of the composite scaffolds. Common chondrogenic markers (SOX9, Col II and Aggrecan) were assessed by Real‐time PCR. Alcian blue staining was performed as well to test possible glycosaminoglycans (GAGs) production. Expressions of mentioned genes and positive staining of GAGs even in those BH/PES groups which were not treated with chondrogenic differentiation medium confirmed the chondro‐inductive potential of composite PES/BH scaffolds. Although BH has an accepted effect on induction of cartilage, incorporating BH with another polymer such as PES and enhancing the mechanical properties, and thus easier handling of the scaffold can be an effective step in making niche‐like scaffolds. [ABSTRACT FROM AUTHOR]

Background and aim: Due to the composite structure of the jaw bone, gelatin and beta-calcium phosphate (β-TCP) biomaterials have been used repeatedly in bone tissue engineering. Despite the desirable properties of scaffolds made, their application has been limited due to their poor mechanical properties and high degradability. The aim of this study was to investigate the effect of clinoptilolite biomaterial with unique mechanical properties such as remarkable mechanical properties, low degradation rate and highly favorable biocompatibility properties in gelatin and β-TCP scaffolds. Material and Method: Preparation of porous scaffold as a template was made leading to freeze drying method using weight percent of 50 for gelatin, 25 β-TCP and 25 Clinoptilolite. SEM analysis and image j software was used in order to evaluation of scaffold surface and finding of porosity frequency. Finally, compressive strength of scaffold was evaluated. Results: In clinoptilolite / β-TCP / Gelatin scaffolds, porosity up to 250 nanometers was recorded which was the best for angiogenesis. In addition to gelatin, clinoptilolite also had a positive effect on porosity. Using compressive strength analysis, increasing of Young's modulus was also observed from 100 to 166 mega Pascal by that Clinoptilolite is the most effective agent in modifying this modulus. Conclusion: Considering the results, clinoptilolite that in addition to improving and enhancing the mechanical properties of composite scaffolds, had a significant effect on the increase in the size and porosity of jaw bone tissue engineering scaffolds. According to the obtained characteristics it can be said that the sample presented is in accordance with the properties of extracellular scaffold (ECM) of jaw bone tissue and would be a suitable choice in tissue engineering of this type of bone. [ABSTRACT FROM AUTHOR]

BACKGROUND: Repair materials for bone tissue engineering should hold good biocompatibility and degradability. There are various related studies, but the Chinese medicine composite cellular bioscaffolds are little reported. OBJECTIVE: To detect the in vitro cytotoxicity of rabbit bone marrow mesenchymal stem cells-cuttlebone bioscaffold based on the Biological Evaluation of Medical Device, and assess its cytotoxicity level in order to provide the theoretical support for its clinical application. METHODS: Bone marrow mesenchymal stem cells-cuttlebone bioscaffold extract was prepared according to an ISO standard — material area: extraction medium volume = 3-6 cm²:1 mL. L-929 cell suspension was prepared, and the cells were then cultured with a density of 1×107/L. There were three groups: positive group (DMEM medium containing phenol), experimental group (material extract), and negative group (DMEM culture medium). The absorbance value of L-929 cells was detected by MTT assay after 24, 48 and 72 hours of culture. The relative proliferation rate of cells was then calculated and the toxicity level was valued in each group. RESULTS AND CONCLUSION: The absorbance values in the experimental, negative and positive groups were not exactly same at different time points (P=0.000 < 0.01). The absorbance values in the experimental and negative groups were significantly higher than those in the positive group (P < 0.01). The cytotoxicity of bone marrow mesenchymal stem cells-cuttlebone bioscaffold was grade 1. To conclude, the bone marrow mesenchymal stem cells-cuttlebone bioscaffold has no obvious toxic effects, and meets the requirements of biomaterial application. [ABSTRACT FROM AUTHOR]

Growth factor-mediated healing of rotator cuff tendon requires to develop a clinically applicable biomaterial playing roles of mechanical support and growth factor release in vivo. In this study, the alginate (AG) nonwoven-sponge composite scaffold (AGNWSP) was fabricated through the formation of an AG sponge layer on the AG nonwoven scaffold (AGNW) surface, and rotator cuff repair with the AG-based scaffolds containing transforming growth factor-beta 1 (TGF-β1) was investigated with a rabbit model. AGNWSP had higher tensile strength, lower bioabsorbability, and higher sustained TGF-β1 release capacity than AGNW, which were highly correlated with tendon regeneration. AGNW and AGNWSP were fixed to the ruptured tendon-to-bone sites, and fresh solutions of TGF-β1 were injected into the scaffolds. When AGNWSP was applied, the repaired supraspinatus tendon had higher ultimate failure load and stress. In addition, well-organized collagen fibers and fibrocartilages were observed at the tendon-to-bone interface in this case. It is suggested that high degree of ruptured rotator cuff healing could be achieved with AGNWSP in combination with TGF-β1. [ABSTRACT FROM AUTHOR]

Here, we demonstrated the fabrication of a composite scaffold (chitosan [CS], collagen [Col], and hydroxyapatite [HA]) with the incorporation of encapsulated Cissus quadrangularis (CQ) extract for tissue engineering applications. First, the crude extract of CQ loaded nanoparticles were synthesized via double emulsion technique using polycaprolactone (PCL) and polyvinyl alcohol (PVA) as oil and aqueous phases, respectively. Both PCL (20, 40, and 80 mg/mL) and PVA (0.5%, 1%, and 3% w/v) concentrations were varied to determine the optimum concentrations for CQ‐loaded nanoparticle preparation. The CQ‐loaded PCL nanoparticles (CQ‐PCL NPs), prepared with 20 mg/mL PCL and 0.5% (w/v) PVA, exhibited the smallest size of 334.22 ± 43.21 nm with 95.54 ± 1.49% encapsulation efficiency. Then, the CQ‐PCL NPs were incorporated into the CS/Col/HA scaffolds. These scaffolds were also studied for their ultrastructure, pore sizes, chemical composition, compressive modulus, water swelling, weight loss, and biocompatibility. The results showed that the addition of CQ‐PCL NPs into the scaffolds did not dramatically alter the ultrastructure and properties of the scaffolds, compared to CS/Col/HA scaffolds alone. However, incorporation of CQ‐PCL NPs in the scaffolds improved the release profile of CQ by preventing the initial burst release and prolonging the release rate of CQ. In addition, the CQ‐PCL NPs‐loaded CS/Col/HA scaffolds supported the attachment and proliferation of MC3T3‐E1 osteoblast cells. [ABSTRACT FROM AUTHOR]

This work reports the fabrication and characterizations of porous scaffold made up of polylactic acid (PLA) with the inclusion of pectin (1, 3, 5, 7, 9, 11 wt%) for potential tissue engineering material. The composite scaffold was prepared using a facile method of freeze extraction. Based on the physical evaluations, the scaffold was suggested to be optimum at 5 wt% of pectin loading. Water contact angle of the scaffold was significantly reduced to 46.5o with the inclusion of 5 wt% of pectin. Morphological and topographic of the PLA scaffold revealed that the pectin induced more porous structure and its surface became rougher which was suitable for cell attachment and proliferation. In vitro studies of the PLA/pectin composite scaffold using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidelt (MTT) assay revealed good biocompatibility whereas Live-Dead kit assay resulted in 91% cell viability after 7 days of incubation. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing technology provides an effective alternative for tissue engineering scaffold. In this paper, a composite scaffold composed of polylactic acid (PLA) film and 3D printing scaffold was fabricated which could provide structural and mechanical support for tissue application. The effects of PLA film/3D printing composite scaffold on scaffold morphology, average diameter, pore diameter, mechanical properties, themal conductivity, electrical conductivity, and surface hydrophilicity were characterized. PLA film/3D printing composite scaffold had larger thickness, better mechanical and thermal conductivity properties in comparison with pure PLA film and 3D printed scaffold. These results suggested that composite scaffold with relatively good overall performance could be a potential candidate for tissue engineering application. [ABSTRACT FROM AUTHOR]

Irreversible electroporation (IRE) is an emerging technology for non-thermal ablation of solid tumors. This study sought to integrate electrodes into microporous poly(caprolactone) (PCL) scaffolds previously shown to recruit metastasizing cancer cells in vivo in order to facilitate application of IRE to disseminating cancer cells. As the ideal parallel plate geometry would render much of the porous scaffold surface inaccessible to infiltrating cells, numerical modeling was utilized to predict the spatial profile of electric field strength within the scaffold for alternative electrode designs. Metal mesh electrodes with 0.35 mm aperture and 0.16 mm wire diameter established electric fields with similar spatial uniformity as the parallel plate geometry. Composite PCL-IRE scaffolds were fabricated by placing cylindrical porous PCL scaffolds between two PCL dip-coated stainless steel wire meshes. PCL-IRE scaffolds exhibited no difference in cell infiltration in vivo compared to PCL scaffolds. In addition, upon application of IRE in vivo, cells infiltrating the PCL-IRE scaffolds were successfully ablated, as determined by histological analysis 3 days post-treatment. The ability to establish homogeneous electric fields within a biomaterial that can recruit metastatic cancer cells, especially when combined with immunotherapy, may further advance IRE technology beyond solid tumors to the treatment of systemic cancer. [ABSTRACT FROM AUTHOR]

N. sativa is an interesting source of bioactive compounds commonly used for various therapeutic purposes. Associate its seeds extracts with biomaterials to improve their antimicrobial properties are highly demanded. This study aims to investigate the encapsulation of NS extracts in hydroxyapatite nanoparticle sodium silicate glass (nHap/SSG) scaffold. NS essential oil (HS) was extracted by hydrodistillation, while hexane (FH) and acetone extracts (FA) were obtained using Soxhlet extraction. (FH) was the most abundant (34%) followed by (FA) (2.02%) and (HS) (1.2%). GC-MS chromatography showed that the (HS) contained beta cymene, alpha thujene, β-pinene and thymoquinone, while (FH) had mostly fatty acids and (FA) decane, 2.9-dimethyl, benzene 1,3,3-trimethylnonyl and beta cymene. Loaded nHap/SGG scaffolds with various amount of (FH), (HS) and (FA) at 1.5, 3, and 6 wt%; were elaborated then characterized by ATR-FTIR, X-ray and SEM techniques and their antimicrobial activity was studied. Samples loaded with 1.5 wt% HE was highly active against C. albicans (19 mm), and at 3 wt% on M. luteus (20 mm) and S. aureus (20 mm). Additionally, loaded scaffolds with 1.5 wt% AE had an important activity against M. luteus (18.9 mm) and S. aureus (19 mm), while the EO had low activities on all bacterial strains. The outcome of this finding indicated that loaded scaffolds demonstrated an important antimicrobial effect that make them promising materials for a wide range of medical applications.