CS Scaffolds Research Articles

Bone regeneration driven by a nano-hydroxyapatite/chitosan composite bioaerogel for periodontal regeneration.

The most recent progress in reconstructive therapy for the management of periodontitis and peri-implantitis bone defects has relied on the development of highly porous biodegradable bioaerogels for guided bone regeneration. The objective of this work was to evaluate in vitro the osteoinduction of periodontal-originating cells (human dental follicle mesenchymal cells, DFMSCs) promoted by a nano-hydroxyapatite/chitosan (nHAp/CS) bioaerogel, which was purified and sterilized by a sustainable technique (supercritical CO2). Moreover, the in vivo bone regeneration capacity of the nHAp/CS bioaerogel was preliminarily assessed as a proof-of-concept on a rat calvaria bone defect model. The quantification of DNA content of DFMSCs seeded upon nHAp/CS and CS scaffolds (control material) showed a significant increase from the 14th to the 21st day of culture. These results were corroborated through confocal laser scanning microscopy analysis (CLSM). Furthermore, the alkaline phosphatase (ALP) activity increased significantly on the 21st day, similarly for both materials. Moreover, the presence of nHAp promoted a significantly higher expression of osteogenic genes after 21days when compared to CS scaffolds and control. CLSM images of 21days of culture also showed an increased deposition of OPN over the nHAp/CS surface. The in vivo bone formation was assessed by microCT and histological analysis. The in vivo evaluation showed a significant increase in bone volume in the nHAp/CS test group when compared to CS and the empty control, as well as higher new bone formation and calcium deposition within the nHAp/CS structure. Overall, the present study showed that the nHAp/CS bioaerogel could offer a potential solution for periodontal and peri-implant bone regeneration treatments since the in vitro results demonstrated that it provided favorable conditions for DFMSC proliferation and osteogenic differentiation, while the in vivo outcomes confirmed that it promoted higher bone ingrowth.

Adaptable test bench for ASTM-compliant permeability measurement of porous scaffolds for tissue engineering

Intrinsic permeability describes the ability of a porous medium to be penetrated by a fluid. Considering porous scaffolds for tissue engineering (TE) applications, this macroscopic variable can strongly influence the transport of oxygen and nutrients, the cell seeding process, and the transmission of fluid forces to the cells, playing a crucial role in determining scaffold efficacy. Thus, accurately measuring the permeability of porous scaffolds could represent an essential step in their optimization process. In literature, several methods have been proposed to characterize scaffold permeability. Most of the currently adopted approaches to assess permeability limit their applicability to specific scaffold structures, hampering protocols standardization, and ultimately leading to incomparable results among different laboratories. The content of novelty of this study is in the proposal of an adaptable test bench and in defining a specific testing protocol, compliant with the ASTM International F2952-22 guidelines, for reliable and repeatable measurements of the intrinsic permeability of TE porous scaffolds. The developed permeability test bench (PTB) exploits the pump-based method, and it is composed of a modular permeability chamber integrated within a closed-loop hydraulic circuit, which includes a peristaltic pump and pressure sensors, recirculating demineralized water. A specific testing protocol was defined for characterizing the pressure drop associated with the scaffold under test, while minimizing the effects of uncertainty sources. To assess the operational capabilities and performance of the proposed test bench, permeability measurements were conducted on PLA scaffolds with regular (PS) and random (RS) micro-architecture and on commercial bovine bone matrix-derived scaffolds (CS) for bone TE. To validate the proposed approach, the scaffolds were as well characterized using an alternative test bench (ATB) based on acoustic measurements, implementing a blind randomized testing procedure. The consistency of the permeability values measured using both the test benches demonstrated the reliability of the proposed approach. A further validation of the PTB’s measurement reliability was provided by the agreement between the measured permeability values of the PS scaffolds and the theory-based predicted permeability value. Once validated the proposed PTB, the performed measurements allowed the investigation of the scaffolds’ transport properties. Samples with the same structure (guaranteed by the fused-deposition modeling technique) were characterized by similar permeability values, and CS and RS scaffolds showed permeability values in agreement with the values reported in the literature for bovine trabecular bone. In conclusion, the developed PTB and the proposed testing protocol allow the characterization of the intrinsic permeability of porous scaffolds of different types and dimensions under controlled flow regimes, representing a powerful tool in view of providing a reliable and repeatable framework for characterizing and optimizing scaffolds for TE applications.

Amorphous magnesium phosphate-graphene oxide nano particles laden 3D-printed chitosan scaffolds with enhanced osteogenic potential and antibacterial properties

The utilization of 3D printing technology for the fabrication of graft substitutes in bone repair holds immense promise. However, meeting the requirements for printability, bioactivity, mechanical strength, and biological properties of 3D printed structures concurrently poses a significant challenge. In this study, we introduce a novel approach by incorporating amorphous magnesium phosphate-graphene oxide (AMP-GO) into a thermo-crosslinkable chitosan/β glycerol phosphate (CS/GP) ink. We fabricated thermo-crosslinkable CS inks containing varying concentrations (10 %, 20 %, or 30 % weight) of AMP-GO. The 3D printed scaffolds incorporating 20 % AMP-GO exhibited significantly improved mechanical properties, with compressive strengths of 4.5 ± 0.06 MPa compared to 0.5 ± 0.03 MPa for CS printed scaffolds. Moreover, the CS/AMP-GO inks demonstrated enhanced antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria, attributed to the release of magnesium cations and the performance of GO. Additionally, CS/20AMP-GO ink facilitated increased adhesion, viability, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs), as evidenced by the upregulation of ALP, COL1, and Runx2 expression, which were elevated 9.8, 6.5, and >22 times, respectively, compared to pure CS scaffolds. Considering its exceptional in vivo osteogenic potential, we anticipate that the CS/20AMP-GO ink holds great potential for 3D printing of bone grafts.

Electrical Stimulation of Human Mesenchymal Stem Cells on Conductive Substrates Promotes Neural Priming.

Electrical stimulation (ES) within a conductive scaffold is potentially beneficial in encouraging the differentiation of stem cells toward a neuronal phenotype. To improve stem cell-based regenerative therapies, it is essential to use electroconductive scaffolds with appropriate stiffnesses to regulate the amount and location of ES delivery. Herein, biodegradable electroconductive substrates with different stiffnesses are fabricated from chitosan-grafted-polyaniline (CS-g-PANI) copolymers. Human mesenchymal stem cells (hMSCs) cultured on soft conductive scaffolds show a morphological change with significant filopodial elongation after electrically stimulated culture along with upregulation of neuronal markers and downregulation of glial markers. Compared to stiff conductive scaffolds and non-conductive CS scaffolds, soft conductive CS-g-PANI scaffolds promote increased expression of microtubule-associated protein 2 (MAP2) and neurofilament heavy chain (NF-H) after application of ES. At the same time, there is a decrease in the expression of the glial markers glial fibrillary acidic protein (GFAP) and vimentin after ES. Furthermore, the elevation of intracellular calcium [Ca2+ ] during spontaneous, cell-generated Ca2+ transients further suggests that electric field stimulation of hMSCs cultured on conductive substrates can promote a neural-like phenotype. The findings suggest that the combination of the soft conductive CS-g-PANI substrate and ES is a promising new tool for enhancing neuronal tissue engineering outcomes.

MP65-20 SMALL MOLECULE-DIRECTED BLADDER TISSUE REGENERATION

You have accessJournal of UrologyCME1 Apr 2023MP65-20 SMALL MOLECULE-DIRECTED BLADDER TISSUE REGENERATION Mitali Kini, Matthew Bury, Natalie Fuller, Larry Wang, Tiffany Sharma, and Arun Sharma Mitali KiniMitali Kini More articles by this author , Matthew BuryMatthew Bury More articles by this author , Natalie FullerNatalie Fuller More articles by this author , Larry WangLarry Wang More articles by this author , Tiffany SharmaTiffany Sharma More articles by this author , and Arun SharmaArun Sharma More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003323.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Co-seeded mesenchymal stem cell (MSC)/CD34+ hematopoietic stem cell (HSC) citrate based scaffolds (CBS) have been successfully utilized to regenerate bladder tissue. However, the acquisition and downstream utility of these cells remains an obstacle. Here, we compare the bladder tissue regenerative capacity of the small molecule PRKR against MSC/HSC seeded CBS in a rat bladder augmentation model. METHODS: Nude rats underwent an∼75% bladder cystectomy then augmented with a CBS and then 1) instilled with saline (SAL, n=7); 2) instilled with PRKR 1x/week for 2 weeks (n=7); or 3) seeded with human MSC/CD34+ HSCs (CS, n=4). Animals were sacrificed 10 weeks post-augmentation. Quantitative morphometrics was used to assess regenerated tissue with regards to muscle content, urothelium width, and vascularization via histology. Peripheral nerve regeneration was assessed by βIII tubulin staining. Urodynamic studies (UDS) and capacity measures were performed pre- and 10 weeks post-augmentation. RESULTS: SAL instilled animals demonstrated 24.50±2.27% muscle content while PRKR and CS instilled animals were 47.00±1.81% and 50.72±1.67% muscle content, respectively. PRKR vs SAL was p<0.0001 and CS vs SAL was p<0.0001. Urothelium width (µm) measurements demonstrated that SAL maintained a 40.82±2.15µm width where PRKR and CS constructs were 52.98±2.55 µm and 59.38±5.07µm in width, respectively. PRKR vs SAL p<0.05; CS vs SAL p<0.01. There was no statistical significance between PRKR and CS groups. Furthermore, SAL instilled animals demonstrated 1.49±0.13% vascularization while PRKR instilled and CS animals were 3.60±0.24% and 4.76±0.34% vascularization, respectively. PRKR vs SAL and CS vs SAL was p<0.0001 and PRKR vs CS groups was p<0.05. With regards to UDS, SAL instilled animals demonstrated an approximate return to pre-augmentation intravesical pressure (40cm H2O) at 10 weeks post-augmentation. PRKR instilled animals showed a decrease in pressure reaching ∼25cm H2O. Similarly, CS animals returned to pre-augmentation values. Regarding percent bladder recovery, PRKR vs SAL was p<0.0001 (206.93±11.93% vs 80.28±5.61%) and CS vs SAL was p<0.0001 (111.13±2.67% vs 80.28±5.61%). There was a statistical significance between PRKR and CS groups, p<0.0001. In all studies, p<0.05 was considered statistically significant and data represents means±SE. βIII tubulin staining was evident in PRKR and CS groups but diminished in SAL groups. CONCLUSIONS: Data demonstrate that PRKR can be used in lieu of CS scaffolds and may also provide an alternative to bladder augmentation enterocystoplasty. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e899 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mitali Kini More articles by this author Matthew Bury More articles by this author Natalie Fuller More articles by this author Larry Wang More articles by this author Tiffany Sharma More articles by this author Arun Sharma More articles by this author Expand All Advertisement PDF downloadLoading ...

Nacre-mimetic hydroxyapatite/chitosan/gelatin layered scaffolds modifying substance P for subchondral bone regeneration

Nacre, exhibiting excellent mechanical strengths due to its hierarchical structures, becomes a potential model to design bone implants. Herein, we firstly fabricated nacre-mimetic hydroxyapatite/chitosan/gelatin (HA/CS/Gel) layered scaffolds and incorporated substance P (SP) peptides. The CS scaffolds with a layered architecture could regulate the deposition of HA nanoplates on the interlamellar CS sheets by using CaCO3 as precursors. The HA/CS/Gel layered scaffolds exhibited a great flexure strength of 11.42 MPa due to a brick-and-mortar structure. The biocompatible components, layered macropores and SP peptides in the HA/CS/Gel therapeutic scaffolds facilitated the spreading and proliferation mesenchymal stem cells (MSCs). Notably, the incorporation of SP peptides induced MSC osteogenic differentiation and extracellular matrix mineralization. Rabbit knee subchondral defect models further proved that the HA/CS/Gel-SP layered scaffolds promoted in vivo subchondral bone regeneration. Hence, the combination of nacre-mimetic bone implants and therapeutic drugs may become an attractive strategy for subchondral bone regeneration.

Preparation and properties of a highly dispersed nano-hydroxyapatite colloid used as a reinforcing filler for chitosan.

Hydroxyapatite/chitosan (HAp/CS) composites have been widely studied and applied in tissue engineering fields due to their excellent biocompatibility and degradability. However, to improve the mechanical properties of CS, cross-linking agents are commonly added, which will seriously affect its biocompatibility and safety. In this study, the homogenously dispersed nano-hydroxyapatite (nHAp) colloidal solution was first synthesized using a co-precipitation method. The three-dimensional porous nano-hydroxyapatite/chitosan (nHAp/CS) composite scaffolds with different nHAp contents were then obtained through an environmentally friendly freeze-drying process without any cross-linking. The microstructure, porosity, phase composition, swelling ratio, mechanical properties, and biocompatibility of the nHAp/CS scaffolds were thoroughly investigated. The as-prepared nHAp/CS scaffolds exhibited a high porosity and excellent swelling performance. Compared with pure CS scaffolds, the nHAp/CS composite scaffolds not only showed higher compressive modulus but also exhibited better biocompatibility. This study provides a simple and environmentally friendly technique to construct three-dimensional porous nHAp/CS composite scaffolds, which demonstrate promising potential by being a scaffold material for bone tissue engineering.

Tissue Engineering Scaffolds Derived from Chitosan

Background: Chitosan, a naturally occurring polymer, is a non-toxic, biocompatible, and biodegradable, and has drawn much attention in the recent years for its use as scaffold material either as alone or in a combination with other materials in tissue engineering. In addition, these chitosan-based scaffolds are able to bind bioactive factors, preserve cells phenotype, control gene expression, synthesize and depose tissue-specific extracellular matrix during tissue regeneration. Objective: We hope it will be helpful to the researchers working in the field of tissue engineering and regenerative medicine. Method: In this review, we highlight the properties, modification and fabrication of innovative CS-based scaffolds for TE application. This review also provides an overview of the current status and the most likely directions of CS scaffolds for tissues such as bone, cartilage, nerve, vascular and other applications. Conclusion: Chitosan-based materials have been widely studied as potential scaffolds for bone, cartilage, nerve, vascular tissue and other tissue regeneration, due to the desirable physical, chemical and biological properties. However, more challenges on mechanical properties, fabrication, bioactivity and other performance are still existed. Keywords: Chitosan, tissue engineering, modification, fabrication, application, scaffolds.

Novel fiber-based pure chitosan scaffold for tendon augmentation: biomechanical and cell biological evaluation

One possibility to improve the mechanical properties after tendon ruptures is augmentation with a scaffold. Based on wet spinning technology, chitosan fibres were processed to a novel pure high-grade multifilament yarn with reproducible quality. The fibres were braided to obtain a 3D tendon scaffold. The CS fibres and scaffolds were evaluated biomechanically and compared to human supraspinatus (SSP) tendons. For the cytobiological characterization, in vitro cell culture experiments with human mesenchymal stem cells (hMSC) were performed. Three types of 3D circular braided scaffolds were fabricated. Significantly, higher ultimate stress values were measured for scaffold with larger filament yarn, compared to scaffold with smaller filament yarn. During cultivation over 28 days, the cells showed in dependence of isolation method and/or donor a doubling or tripling of the cell number or even a six-fold increase on the CS scaffold, which was comparable to the control (polystyrene) or in the case of cells obtained from human biceps tendon even higher proliferation rates. After 14 days, the scaffold surface was covered homogeneously with a cell layer. In summary, the present work demonstrates that braided chitosan scaffolds constitute a straightforward approach for designing tendon analogues, maintaining important flexibility in scaffold design and providing favourable mechanical properties of the resulting construct.

Repairing calvarial defects with biodegradable polycaprolactone-chitosan scaffolds fabricated using the melt stretching and multilayer deposition technique.

The ability to repair bone defects of polycaprolactone-chitosan scaffolds containing 20% chitosan (PCL-20%CS) fabricated using the melt stretching and multilayer deposition (MSMD) technique was assessed and compared with commercial scaffolds. Two calvarium defects of 11mm in diameter were created in each of the fifteen New Zealand white rabbits. The PCL-20%CS scaffolds were implanted in one site (group A) while another site was performed with PCL-tricalcium phosphate (TCP) scaffolds containing 20% TCP (PCL-20%TCP) fabricated by fused deposition modeling technique (FDM) (group B). At two, four and eight weeks thereafter, new bone regeneration within the defects was assessed using histomorphometric and micro-computed tomography (µ-CT) analysis. The result of histological sections demonstrated that chronic inflammatory reaction was generally detected along scaffolds of group A, but it was not found in group B. Over 8 weeks, the µ-CT analysis indicated that the average amount of new bone of group A was slightly less than that of group B (p>0.05). In conclusion, efficacy of the PCL-20%CS MSMD scaffolds for repairing bone defects was less than that of the PCL-20%TCP FDM scaffolds. However, MSMD scaffolding is still the technique of choice, but needed some modifications.

Hollow hydroxyapatite microspheres/chitosan composite as a sustained delivery vehicle for rhBMP-2 in the treatment of bone defects.

Composite scaffold comprised of hollow hydroxyapatite (HA) and chitosan (designated hHA/CS) was prepared as a delivery vehicle for recombinating human bone morphogenetic protein-2 (rhBMP-2). The in vitro and in vivo biological activities of rhBMP2 released from the composite scaffold were then investigated. The rhBMP-2 was firstly loaded into the hollow HA microspheres, and then the rhBMP2-loaded HA microspheres were further incorporated into the chitosan matrix. The chitosan not only served to bind the HA microspheres together and kept them at the implant site, but also effectively modified the release behavior of rhBMP-2. The in vitro release and bioactivity analysis confirmed that the rhBMP2 could be loaded and released from the composite scaffolds in bioactive form. In addition, the composite scaffolds significantly reduced the initial burst release of rhBMP2, and thus providing prolonged period of time (as long as 60 days) compared with CS scaffolds. In vivo bone regenerative potential of the rhBMP2-loaded composite scaffolds was evaluated in a rabbit radius defect model. The results revealed that the rate of new bone formation in the rhBMP2-loaded hHA/CS group was higher than that in both negative control and rhBMP2-loaded CS group. These observations suggest that the hHA/CS composite scaffold would be effective and feasible as a delivery vehicle for growth factors in bone regeneration and repair.

Synthesis and characterization of a nano‐hydroxyapatite/chitosan/polyethylene glycol nanocomposite for bone tissue engineering

A novel nanocomposite involving nano‐hydroxyapatite/chitosan/polyethylene glycol (n‐HAP/CS/PEG) has been successfully synthesized via co‐precipitation approach at room temperature. The purpose to synthesize such nanocomposite is to search for an ideal analogue which may mimick the composition of natural bone for bone tissue engineering with respect to suitable biocompatibility, cytotoxicity and mechanical properties. The FTIR spectra of n‐HAP/CS and n‐HAP/CS/PEG scaffolds indicated significant intermolecular interaction between the various components of both the nanocomposites. The results of XRD, TEM and TGA/DTA suggested that the crystallinity and thermal stability of the n‐HAP/CS/PEG scaffold have decreased and increased respectively, relative to n‐HAP/CS scaffold. The comparison of SEM images of both the scaffolds indicated that the incorporation of PEG influenced the surface morphology while a better in‐vitro bioactivity has been observed in n‐HAP/CS/PEG than in n‐HAP/CS based on SBF study, referring a greater possibility for making direct bond to living bone if implanted. Furthermore, MTT assay revealed superior non‐toxic nature of n‐HAP/CS/PEG to murine fibroblast L929 cells as compared to n‐HAP/CS. The comparative swelling studies of n‐HAP/CS/PEG and n‐HAP/CS scaffolds revealed a better swelling rate for n‐HAP/CS/PEG. Also n‐HAP/CS/PEG showed higher mechanical strength relative to n‐HAP/CS supportive of bone tissue ingrowths. Copyright © 2014 John Wiley &amp; Sons, Ltd.

Engineering scaffolds integrated with calcium sulfate and oyster shell for enhanced bone tissue regeneration.

Engineering scaffolds combinging natural biomineral and artificially synthesized material hold promising potential for bone tissue regeneration. In this study, novel bioactive calcium sulfate/oyster shell (CS/OS) composites were prepared. Comparing to CS scaffold, the CS/OS composites with a controllable degradation rate displayed enhanced mineral nodule formation, higher alkaline phosphate (ALP) activity and increased proliferation rate while treated osteocytes. In CS/OS composites group, elevated mRNA levels of key osteogenic genes including bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), osterix (Osx), and osteocalcin (OCN) were observed. Furthermore, The up-regulation of BMP-2 and type I collagen (COL-I) was observed for CS/OS composites relative to a CS group. Scaffolds were implanted into critical-sized femur cavity defects in rabbits to investigate the osteogenic capacity of the composites in vivo. The CS/OS scaffolds with proper suitable times and mechanical strength strongly promoted osteogenic tissue regeneration relative to the regeneration capacity of CS scaffolds, as indicated by the results of histological staining. These results suggest that the OS-modified CS engineering scaffolds with improved mechanical properties and bioactivity would facilitate the development of a new strategy for clinic bone defect regeneration.

Ectopic osteogenesis and scaffold biodegradation of tissue engineering bone composed of chitosan and osteo-induced bone marrow mesenchymal stem cells in vivo

Background Chitosan (CS) scaffolds combined with osteogenically induced bone marrow mesenchymal stem cells (BMSCs) have been proved to be promising substitutes for repairing bone defects. Nevertheless, the bone-forming and scaffold-biodegrading processes are seldom studied. This study aimed to determine the osteogenic ability of CS/osteo-induced BMSC composites by observing the bone-forming process and explore the relationship between bone formation and scaffold biodegradation. Methods The CS/osteo-induced BMSC composites (CS+cells group) and the CS scaffolds (CS group) were, respectively, implanted into SD rat thigh muscles. At 2, 4, 6, 8, and 12 weeks postoperatively, the rat femurs were scanned by CT, and the CT values of the implants were measured and comparatively analyzed. Subsequently, the implants were harvested and stained with hematoxylin and eosin and Masson trichrome, and the percentages of bone area, scaffold area, and collagen area were calculated and compared between the two groups. Results The imaging results showed that the densities of implants of the two groups gradually increased along with time, but the CT values of implants in the CS+cells group were much higher than in the CS group at the same time point (P &lt;0.05). The histological results showed that the de novo bone and collagen formed in the pores of the scaffolds and gradually increased since 2 weeks postoperation in both groups, and the scaffold gradually degraded along with the boneforming process. However, the comparative analysis results showed that the CS+cells group gained more de novo bone and collagen formation and had less scaffold than the CS group at the same time point (P &lt;0.05). Conclusion The CS/osteo-induced BMSC composites are excellent bone tissue engineering substitutes, and the scaffold biodegradation is accordant with the bone formation.

Nanosized mesoporous bioactive glass/poly(lactic-co-glycolic acid) composite-coated CaSiO3 scaffolds with multifunctional properties for bone tissue engineering.

It is of great importance to prepare multifunctional scaffolds combining good mechanical strength, bioactivity, and drug delivery ability for bone tissue engineering. In this study, nanosized mesoporous bioglass/poly(lactic-co-glycolic acid) composite-coated calcium silicate scaffolds, named NMBG-PLGA/CS, were successfully prepared. The morphology and structure of the prepared scaffolds were characterized by scanning electron microscopy and X-ray diffraction. The effects of NMBG on the apatite mineralization activity and mechanical strength of the scaffolds and the attachment, proliferation, and alkaline phosphatase activity of MC3T3 cells as well as drug ibuprofen delivery properties were systematically studied. Compared to pure CS scaffolds and PLGA/CS scaffolds, the prepared NMBG-PLGA/CS scaffolds had greatly improved apatite mineralization activity in simulated body fluids, much higher mechanical property, and supported the attachment of MC3T3 cells and enhanced the cell proliferation and ALP activity. Furthermore, the prepared NMBG-PLGA/CS scaffolds could be used for delivering ibuprofen with a sustained release profile. Our study suggests that the prepared NMBG-PLGA/CS scaffolds have improved physicochemical, biological, and drug-delivery property as compared to conventional CS scaffolds, indicating that the multifunctional property of the prepared scaffolds for the potential application of bone tissue engineering.

3D-printing of highly uniform CaSiO3 ceramic scaffolds: preparation, characterization and in vivo osteogenesis

Calcium silicate (CaSiO3, CS) ceramics have received significant attention for application in bone regeneration due to their excellent in vitro apatite-mineralization ability; however, how to prepare porous CS scaffolds with a controllable pore structure for bone tissue engineering still remains a challenge. Conventional methods could not efficiently control the pore structure and mechanical strength of CS scaffolds, resulting in unstable in vivo osteogenesis. The aim of this study is to set out to solve these problems by applying a modified 3D-printing method to prepare highly uniform CS scaffolds with controllable pore structure and improved mechanical strength. The in vivo osteogenesis of the prepared 3D-printed CS scaffolds was further investigated by implanting them in the femur defects of rats. The results show that the CS scaffolds prepared by the modified 3D-printing method have uniform scaffold morphology. The pore size and pore structure of CS scaffolds can be efficiently adjusted. The compressive strength of 3D-printed CS scaffolds is around 120 times that of conventional polyurethane templated CS scaffolds. 3D-Printed CS scaffolds possess excellent apatite-mineralization ability in simulated body fluids. Micro-CT analysis has shown that 3D-printed CS scaffolds play an important role in assisting the regeneration of bone defects in vivo. The healing level of bone defects implanted by 3D-printed CS scaffolds is obviously higher than that of 3D-printed β-tricalcium phosphate (β-TCP) scaffolds at both 4 and 8 weeks. Hematoxylin and eosin (H&E) staining shows that 3D-printed CS scaffolds induce higher quality of the newly formed bone than 3D-printed β-TCP scaffolds. Immunohistochemical analyses have further shown that stronger expression of human type I collagen (COL1) and alkaline phosphate (ALP) in the bone matrix occurs in the 3D-printed CS scaffolds than in the 3D-printed β-TCP scaffolds. Considering these important advantages, such as controllable structure architecture, significant improvement in mechanical strength, excellent in vivo osteogenesis and since there is no need for second-time sintering, it is indicated that the prepared 3D-printed CS scaffolds are a promising material for application in bone regeneration.

The effect of poly(lactic-co-glycolic acid) (PLGA) coating on the mechanical, biodegradable, bioactive properties and drug release of porous calcium silicate scaffolds

Ideal scaffolds for bone tissue engineering require 3D interconnected porous structures, enough mechanical strength for hand of treatment as well as proper bioactivity and biodegradability. Calcium silicate (CaSiO3, CS) scaffolds have been studied for bone tissue engineering application due to their excellent bioactivity. However, the main disadvantages of CS scaffolds are their low mechanical strength and high alkaline ionic products. In this study, sintered CS scaffolds were prepared and coated with poly(lactic-co-glycolic acid) (PLGA), and the effect of PLGA coating on the mechanical, biodegradable, bioactive properties and drug release of porous CS scaffolds were investigated. The results showed that the PLGA-coated CS scaffolds maintained large pore size and high porosity. The compressive strength of PLGA/CS scaffolds was significantly improved compared to pure CS scaffolds, and increased with the increase of intrinsic viscosity and concentration of PLGA. In addition, the PLGA coating neutralized alkaline level resulted from the ionic products of CS scaffolds and reduced the pH value of biological solution during the degradation of scaffolds. It was found that PLGA/CS scaffolds still maintained excellent apatite-mineralization ability in SBF. Furthermore, the PLGA coating effectively inhibited the burst release and maintained a sustained release of drugs from the CS scaffolds. Our results indicate that the PLGA/CS scaffolds have great potential for bone tissue engineering application by the virtue of improved mechanical strength, and excellent bioactivity, degradation as well as drug-delivery property.