3D Porous Scaffolds Research Articles

Investigating Cancerous Exosomes' Effects on CD8+ T-Cell IL-2 Production in a 3D Unidirectional Flow Bioreactor Using 3D Printed, RGD-Functionalized PLLA Scaffolds.

Exosomes from cancer cells are implicated in cancer progression and metastasis, carrying immunosuppressive factors that limit the antitumor abilities of immune cells. The development of a real-time, 3D cell/scaffold construct flow perfusion system has been explored as a novel tool in the study of T-cells and exosomes from cancer cells. Exosomes from human lung cancer (H1299 and A549) cells were co-cultured in a unidirectional flow bioreactor with CD8+ T-cells immobilized onto 3D-printed RGD-functionalized poly(L-lactic) acid (PLLA) scaffolds and assessed for IL-2 production. The IL-2 production was investigated for a wide range of T-cell to exosome ratios. With the successful incorporation of the RGD binding motif onto the PLLA surface at controllable densities, CD8+ T-cells were successfully attached onto 2D disks and 3D printed porous PLLA scaffolds. T-cell attachment increased with increasing RGD surface density. The diameter of the attached T-cells was 7.2 ± 0.2 µm for RGD densities below 0.5 nmoles/mm2 but dropped to 5.1 ± 0.3 µm when the RGD density was 2 nmoles/mm2 due to overcrowding. The higher the number of cancer exosomes, the less the IL-2 production by the surface-attached T-cells. In 2D disks, the IL-2 production was silenced for T-cell to exosome ratios higher than 1:10 in static conditions. IL-2 production silencing in static 3D porous scaffolds required ratios higher than 1:20. The incorporation of flow resulted in moderate to significant T-cell detachment. The portions of T-cells retained on the 3D scaffolds after exposure for 4 h to 0.15 or 1.5 mL/min of perfusion flow were 89 ± 11% and 30 ± 8%, respectively. On 3D scaffolds and in the presence of flow at 0.15 ml/min, both H1299 and A549 cancerous exosomes significantly suppressed IL-2 production for T-cell to exosome ratios of 1:1000. The much higher level of exosomes needed to silence the IL-2 production from T-cells cultured under unidirectional flow, compared to static conditions, denotes the importance of the culturing conditions and the hydrodynamic environment, on the interactions between CD8+ T-cells and cancer exosomes.

Genipin-crosslinked collagen scaffolds inducing chondrogenesis: a mechanical and biological characterization.

Articular cartilage degeneration is still an unsolved issue owing to its weak repairing capabilities, which usually result in fibrocartilage tissue formation. This fibrous tissue lacks of structural and bio-mechanical properties, degrading over time. Currently, arthroscopic techniques and autologous transplantation are the most used clinical procedures. However, rather than restoring cartilage integrity, these methods only postpone further cartilage deterioration. Therefore, tissue engineering strategies aimed at selecting scaffolds that remarkably support the chondrogenic differentiation of human mesenchymal stem cells (hMSCs) could represent a promising solution, but they are still challenging for researchers. In this study, the influence of two different genipin (Gp) crosslinking routes on collagen (Coll)-based scaffolds in terms of hMSCs chondrogenic differentiation and biomechanical performances was investigated. Three-dimensional (3D) porous Coll scaffolds were fabricated by freeze-drying techniques and were crosslinked with Gp following a "two-step" and an in "bulk" procedure, in order to increase the physico-mechanical stability of the structure. Chondrogenic differentiation efficacy of hMSCs and biomechanical behavior under compression forces through unconfined stress-strain tests were assessed. Coll/Gp scaffolds revealed an isotropic and highly homogeneous pore distribution along with an increase in the stiffness, also supported by the increase in the Coll denaturation temperature (Td =57-63°C) and a significant amount of Coll and GAG deposition during the 3weeks of chondrogenic culture. In particular, the presence of Gp in "bulk" led to a more uniform and homogenous chondral-like matrix deposition by hMSCs if compared to the results obtained from the Gp "two-step" functionalization procedure.

A MOF-Derivative Decorated Hierarchical Porous Host Enabling Ultrahigh Rates and Superior Long-Term Cycling of Dendrite-Free Zn Metal Anodes.

Aqueous Zn metal batteries have attracted much attention due to their high intrinsic capacity, high safety, and low cost. Nevertheless, uncontrollable dendrite growth and adverse side reactions of Zn anodes seriously hinder their further application. Herein, a three-dimensional (3D) porous graphene-carbon nanotubes scaffold decorated with metal-organic framework derived ZnO/C nanoparticles (3D-ZGC) is fabricated as the host for dendrite-free Zn-metal composite anodes. The zincophilic ZnO/C nanoparticles act as preferred deposition sites with low nucleation barriers to induce homogeneous Zn deposition. The mechanically robust 3D scaffold with high conductivity not only suppresses the formation of dendritic Zn by reducing the local current density and homogenizing Zn2+ ion flux, but also inhibits volume changes during the long-term plating/stripping process. As a result, the 3D-ZGC composite anodes afford unprecedented Zn plating-stripping stability at an ultrahigh current density of 20mA cm-2 for 1500 cycles with low overpotential (<65mV) when used in a symmetric cell. When coupled with MnO2 cathodes, the assembled Zn@3D-ZGC//MnO2 full batteries deliver an enhanced cycling stability for up to 6000 cycles at 2000mAg-1 , demonstrating the potential of the 3D-ZGC composite anode for advanced Zn metal batteries.

Bioadaptive Porous 3D Scaffolds Comprising Cellulose and Chitosan Nanofibers Constructed by Pickering Emulsion Templating

AbstractHighly porous three‐dimensional (3D) scaffolds can mimic the lobular structure of a human liver where hepatocytes are organized. However, 3D scaffolds with uniformly porous and oriented structures are challenging to fabricate without cross‐linking agents. Herein, this work presents a Pickering emulsion‐induced interface approach to construct aligned porous scaffolds for 3D cell cultures through the combined use of surface‐carboxylated cellulose nanofibers and chitosan nanofibers as stabilizers, and freezing/lyophilization to remove the oil phase. The obtained Pickering emulsions exhibit long‐term stability and their droplet sizes are tunable from 2.7 to 10.2 µm. Assembly at the oil–water interface can be modulated by controlling the NaCl dosage and oil phase proportion, resulting in porous foams with tunable porosity and versatile architectures as an in vitro alternative to the native liver microenvironment. The foams are noncytotoxic, confirmed using mouse fibroblast NIH/3T3 cells, and the cells grow both on the surface and in the internal structure of the foam. Notably, the 3D porous scaffolds are favorable microenvironments for the formation of human liver carcinoma HepG2 spheroidal cells, which exhibit liver‐like activity. This strategy based on Pickering emulsion templating provides a new avenue for constructing bioadaptive 3D scaffolds, specifically all‐biomass porous foams, for tissue engineering.

A Combined Lithium Intercalation and Plating Mechanism Using Conductive Carbon‐Fiber Electrodes

AbstractLithium‐metal anodes (LMAs) are desirable for next‐generation rechargeable batteries because of their high energy density. However, in practical applications they are hindered by inhomogeneous and uncontrolled lithium‐dendrite deposition during cycling. Herein, we propose a dual charge storage mechanism, using freestanding carbon‐fiber paper (CFP) with carbon fillers electrode. These CFP electrodes are manufactured at an industrial scale and act both as a host for lithium (Li) intercalation and as a conductive and porous 3D scaffold for Li plating/stripping. The CFP electrode exhibits excellent long‐term cycling stability, as evidenced by Coulombic efficiencies of over 99.5 % on the 250th cycle in CFP|Li half‐cells with a lithiation capacity of 1.5 mA h cm−2 and current density of 0.5 mA cm−2. We also demonstrate that the CFPs are sufficiently electrically conductive to operate in small pouch cells without metal foil current collectors, further improving the energy density of the proposed electrodes.

3D gel-printed porous magnesium scaffold coated with dibasic calcium phosphate dihydrate for bone repair in vivo.

Background/Objective: The treatment of bone defect has always been a difficult problem in orthopedic clinic. The search for alternative biodegradable implants is a hot topic. The development of biodegradable magnesium scaffolds for the treatment of bone defects has long been a goal of the public.MethodsIn this study, we proposed a porous magnesium scaffold prepared by 3D gel printing and surface modification with an additional calcium phosphate coating and use of its strength, degradability and slow degradation rate in a bone graft substitute material. The porous magnesium granular scaffold was prepared by 3D gel printing technology and modified by DCPD (Dibasic Calcium Phosphate Dihydrate) coating. The biocompatibility, degradation rate, and osteogenic ability of the scaffold were evaluated in vitro and in vivo.ResultsThe biocompatibility, in vivo degradation and bone defect healing response of the implants were investigated. Porous magnesium scaffolds were successfully prepared, and the strength of sintered scaffolds reached 5.38 ​MPa. The degradation rates of scaffolds were significantly reduced after coating with DCPD. The cell compatibility evaluation showed that DCPD-coated Mg scaffold was suitable for cell proliferation. In vivo biosafety monitoring showed that scaffold implantation did not cause an increase in Mg ion concentration in vivo, and no toxic damage was detected in the liver or kidney. Micro-CT and pathological results showed that a large amount of new bone was formed at 6 weeks. At 12 weeks, approximately 52% of the scaffold volume remained. At 24 weeks, osteogenesis, which was stimulated by some residual scaffold, still can be observed. In summary, this study suggests that 3D gel-printed DCPD-coated porous magnesium scaffolds have great potential as bone graft alternatives.ConclusionIn summary, this study suggests that 3D gel-printed DCPD-coated porous magnesium scaffolds have great potential as bone graft alternatives.The Translational potential of this articleThe translational potential of this article is to make use of the advantages of 3D gel printing technology with higher efficiency and lower cost compared with SLM and SLS technologies, and use pure magnesium powder as raw material to prepare degradable porous magnesium metal scaffolds, opening up a new technical route for the preparation of degradable porous magnesium scaffolds which are made for bone defect regeneration in the future.

Generation of hybrid tissue engineered construct through embedding autologous chondrocyte loaded platelet rich plasma/alginate based hydrogel in porous scaffold for cartilage regeneration

Over the past decades, various attempts have been made to develop suitable tissue-engineered constructs to repair or regenerate the damaged or diseased articular cartilage. In the present study, we embedded Platelet rich plasma (PRP)/Sodium Alginate (SA) based hydrogel in porous 3D scaffold of chitosan (CH)/chondroitin sulfate (CS)/silk fibroin (SF) to develop hybrid scaffold for cartilage tissue construct generation with abilities to support shape recovery potential, facilitate uniform cells distribution and mimic gel like cartilage tissue extracellular matrix.The developed hybrid matrix shows suitable pore size (55–261 μm), porosity (77 ± 4.3%) and compressive strength (0.13 ± 0.04 MPa) for cartilage tissue construct generation and its applications. The developed SA/PRP-based cartilage construct exhibits higher metabolic activity, glycosaminoglycan deposition, expression of collagen type II, and aggrecan in comparison to SA based cell-scaffold construct. In-vivo animal study was also performed to investigate the biocompatibility and cartilage tissue regeneration potential of the developed construct. The obtained gross analysis of knee sample, micro-computed tomography, and histological analysis suggest that implanted tissue construct possess the superior potential to regenerate hyaline cartilage defect of thickness around 1.10 ± 0.36 mm and integrate with surrounding tissue at the defect site. Thus, the proposed strategy for the development of cartilage tissue constructs might be beneficial for the repair of full-thickness knee articular cartilage defects.

3D Printing of Hierarchically Porous Lattice Structures Based on Åkermanite Glass Microspheres and Reactive Silicone Binder.

The present study illustrates the manufacturing method of hierarchically porous 3D scaffolds based on åkermanite as a promising bioceramic for stereolithography. The macroporosity was designed by implementing 3D models corresponding to different lattice structures (cubic, diamond, Kelvin, and Kagome). To obtain micro-scale porosity, flame synthesized glass microbeads with 10 wt% of silicone resins were utilized to fabricate green scaffolds, later converted into targeted bioceramic phase by firing at 1100 °C in air. No chemical reaction between the glass microspheres, crystallizing into åkermanite, and silica deriving from silicone oxidation was observed upon heat treatment. Silica acted as a binder between the adjacent microspheres, enhancing the creation of microporosity, as documented by XRD, and SEM coupled with EDX analysis. The formation of ‘spongy’ struts was confirmed by infiltration with Rhodamine B solution. The compressive strength of the sintered porous scaffolds was up to 0.7 MPa with the porosity of 68–84%.

Conductive poly(ε‐caprolactone)/polylactic acid scaffolds for tissue engineering applications: Synergy effect of zirconium nanoparticles and polypyrrole

AbstractBiocompatible and electrically conductive porous scaffolds with a desirable hydrophilicity and degradation rate and suitable mechanical performance are highly favorable for tissue engineering and regenerative medicine applications. In this study, we fabricated three‐dimensional (3D) porous bioscaffolds from poly(ε‐caprolactone) and polylactic acid containing different concentrations of zirconia nanoparticles (n‐ZrO2) through freeze‐drying technique. Afterward, the surface of the scaffolds was coated with an electrically conductive layer through in situ polymerization of polypyrrole (PPy) on the samples. Bioscaffolds exhibited a favorable range of mechanical properties and electrical conductivity, meeting the required mechanical performances and conductivity for a broad range of tissue engineering applications. Coating PPy on the scaffolds resulted in significantly higher hydrophilicity and faster biodegradation rate, as well as a noticeable enhancement on the in vitro cell attachment, proliferation, and viability. Our findings indicated that the simultaneous presence of n‐ZrO2 and PPy in the system presents a noticeable synergistic effect in overall properties and introduces the fabricated 3D porous scaffolds as promising candidates for tissue engineering and regenerative medicine applications.

Protein-inorganic hybrid porous scaffolds for bone tissue engineering.

Porous scaffolds hold promise in the treatment of bone defects for bone tissue engineering due to their interconnected porous structure and suitable mechanical properties. Herein, LAPONITE® (LAP), which is able to promote osteogenic differentiation, was introduced into regenerated silk fibroin (RSF) porous scaffolds. Due to hydrogen bonding and electrostatic interactions between RSF and LAP, RSF/LAP 3D porous scaffolds were successfully prepared. The pore size, porosity, and mechanical properties of the RSF/LAP 3D porous scaffolds were modulated during the preparation process. Evaluation of the proliferation of bone marrow mesenchymal stem cells (BMSCs) on the RSF/LAP 3D porous scaffolds in vitro indicated that the addition of LAP improved the adhesion and proliferation of cells. Additionally, alkaline phosphatase activity and osteospecific gene expression analysis showed that the RSF/LAP 3D porous scaffolds enhanced the osteogenic differentiation of BMSCs compared to the pristine RSF porous scaffolds, especially with a higher LAP content. The subcutaneous implantation of the RSF/LAP 3D porous scaffolds in rats demonstrated good histocompatibility in vivo. Therefore, RSF/LAP 3D porous scaffolds with good biocompatibility and biodegradability have good application prospects in the field of bone tissue engineering.

Engineering transplantable human lymphatic and blood capillary networks in a porous scaffold

Due to a relative paucity of studies on human lymphatic assembly in vitro and subsequent in vivo transplantation, capillary formation and survival of primary human lymphatic (hLEC) and blood endothelial cells (hBEC) ± primary human vascular smooth muscle cells (hvSMC) were evaluated and compared in vitro and in vivo. hLEC ± hvSMC or hBEC ± hvSMC were seeded in a 3D porous scaffold in vitro, and capillary percent vascular volume (PVV) and vascular density (VD)/mm2 assessed. Scaffolds were also transplanted into a sub-cutaneous rat wound with morphology/morphometry assessment. Initially hBEC formed a larger vessel network in vitro than hLEC, with interconnected capillaries evident at 2 days. Interconnected lymphatic capillaries were slower (3 days) to assemble. hLEC capillaries demonstrated a significant overall increase in PVV (p = 0.0083) and VD (p = 0.0039) in vitro when co-cultured with hvSMC. A similar increase did not occur for hBEC + hvSMC in vitro, but hBEC + hvSMC in vivo significantly increased PVV (p = 0.0035) and VD (p = 0.0087). Morphology/morphometry established that hLEC vessels maintained distinct cell markers, and demonstrated significantly increased individual vessel and network size, and longer survival than hBEC capillaries in vivo, and established inosculation with rat lymphatics, with evidence of lymphatic function. The porous polyurethane scaffold provided advantages to capillary network formation due to its large (300–600 μm diameter) interconnected pores, and sufficient stability to ensure successful surgical transplantation in vivo. Given their successful survival and function in vivo within the porous scaffold, in vitro assembled hLEC networks using this method are potentially applicable to clinical scenarios requiring replacement of dysfunctional or absent lymphatic networks.

Oriented co-continuous 3D porous scaffolds with inhibited activating functionality: An effective strategy to inhibit the hyperactivation of astrocytes

Astrocyte activation is an important cause of neuropathic pain. Inhibiting the hyperactivation of astrocytes is beneficial to control over neuropathic pain. However, there is a lack of non-pharmaceutical ways to inhibit the hyperactivation of astrocytes. This study aimed at regulating the activity of glial cells via the architecture of 3D porous scaffolds. Herein, the 3D porous scaffolds with co-continuous and oriented pores were prepared via solid-phase stretching of co-continuous polymer blends followed by selective phase extraction. Compared to the isotropic scaffold, the proliferation of astrocytes slowed down on the oriented scaffolds. Meanwhile, the expression of growth factors and inflammatory factors secreted by astrocyte activation was inhibited by the oriented pores. It led to the suppression of the Wnt/β-catenin signaling pathway that is crucial to determine chronic neuropathic pain. Immunofluorescence staining displayed that the hyperactivation of astrocytes was inhibited, and the expression of kindlin-1, a key protein that activates astrocytes, was downregulated. The proposed strategy offers a probable physical means to relieve neuropathic pain.

Anisotropically thermal transfer improvement and shape stabilization of paraffin supported by SiC-coated biomass carbon fiber scaffolds for thermal energy storage

Phase change materials (PCMs) play a promising application in the field of heat management and energy storage, which are restricted by the problems of low thermal conductivity and leakage. In this work, 3D porous carbon scaffolds as-consisted of SiC-wrapped biomass carbon fibers were prepared, which were used as the thermal conductive skeleton and shape stabilizer for paraffin PCM. In particular, the porous carbon scaffolds were designed with 1D arranged carbon fibers and hierarchical pore structure, thereby the resulting composite PCMs indicate anisotropically improved heat transfer and good anti-leakage properties. High thermal conductivity values of 0.61 W m−1 k− 1 in the axial direction (> 3 times of paraffin) and 0.48 W m−1 k−1 in the lateral direction were obtained for the composite with a filler ratio of 10.4 wt%. The composite also presented well-behaved thermal cycling stability and high heat storage capacity (186 J g−1). With a high heat storage capability and anisotropically improved heat transfer properties, the biomass carbon supported PCMs indicate enormous potentials in thermal management applications.

Porous 3D polyurethane composite scaffolds with incorporation of highly mineralized calcium citrate for bone tissue engineering

High mineralization activity is a crucial requirement in bone tissue engineering. In this study, a novel calcium citrate compounded amorphous calcium phosphate (CAP)/polyurethanes (PUs) composite porous 3D scaffold was developed by in situ polymerization via gas foaming method. The physical and chemical properties were characterized and discussed. The results showed that the HDI can react mildly with hydroxyl (–OH) groups of PEG, while gas foaming action was caused by the release of CO2 occurred in the reactive process, resulting in a uniform porous structure of PUs scaffold. The porosities of the synthetic PEGCAP porous scaffolds are all above 70% with high interconnectivity, while the porosity decreased 27% with increasing CAP to 40%. Furthermore, the mechanical properties of porous scaffolds enhanced about 16 times after addition of CAP. After immersing in simulated body fluid (SBF), the surface structure of the porous scaffold kept stable, and surface deposits formed, indicating that the porous scaffold has good mineralization activity. In addition, the in vitro cells proliferation assay confirms the excellent bioactivity of PEGCAP porous scaffolds.

Effects of dynamic flow rates on degradation deposition behavior of Mg scaffold

Degradability of bone tissue engineering scaffold that matching the regeneration rate could allow a complete replacement of host tissue. However, the porous structure of biodegradable Mg scaffolds certainly generated high specific surface area, and the three-dimensional interconnected pores provided fast pervasive invasion entrance for the corrosive medium, rising concern of the structural integrity during the degradation. To clarify the structural evolution of the three-dimensional (3D) porous structure, semi-static immersion tests were carried out to evaluate the degradation performance in our previous study. Nevertheless, dynamic immersion tests mimicking the in vivo circulatory fluid through the interconnected porous structure have yet been investigated. Moreover, the effects of dynamic flow rates on the degradation deposition behavior of 3D porous Mg scaffolds were rarely reported. In this study, Mg scaffolds degraded at three flow rates exhibited different degradation rates and deposition process. A flow rate of 0.5 mL/min introduced maximum drop of porosity by accumulated deposition products. The deposition products provided limited protection against the degradation process at a flow rate of 1.0 mL/min. The three-dimensional interconnected porous structure of Mg scaffold degraded at 2.0 mL/min well retained after 14 days showing the best interconnectivity resistance to the degradation deposition process. The dynamic immersion tests disclosed the reason for the different degradation rates on account of flow rates, which may bring insight into understanding of varied in vivo degradation rates related to implantation sites.

Fabrication of a novel Three-Dimensional porous PCL/PLA tissue engineering scaffold with high connectivity for endothelial cell migration

As an artificial extracellular matrix, tissue engineering scaffolds promote tissue regeneration and repair. Therefore, the scaffold’s internal structure is crucial for cell adhesion, growth, and migration. In this paper, based on the supercritical CO2 foaming technology, a novel three-dimensional (3D) porous polycaprolactone/polylactic acid tissue engineering scaffold induced by heterogeneous nanofibres was prepared by introducing the second phase of polylactic acid electrospinning nanofibres. The scanning electron microscopy results showed that the prepared scaffolds exhibited obvious nanofibre structures and 3D reticular pore structures. The influence of foaming temperature on pore morphology was also systematically explored. Tensile tests and water contact angle tests showed that the novel scaffolds exhibited good mechanical properties and hydrophilicity. The results of cross-sectional human umbilical endothelial cell (HUVEC) culture showed that the scaffolds were biocompatible and significantly promote the adhesion, migration and permeability of HUVECs. Single-cell migration assays showed that the 3D porous scaffolds effectively promote HUVEC migration. Therefore, 3D porous scaffolds have enormous application potential in the field of vascular patches.

Precision 3D printed meniscus scaffolds to facilitate hMSCs proliferation and chondrogenic differentiation for tissue regeneration

BackgroundThe poor regenerative capability and structural complexity make the reconstruction of meniscus particularly challenging in clinic. 3D printing of polymer scaffolds holds the promise of precisely constructing complex tissue architecture, however the resultant scaffolds usually lack of sufficient bioactivity to effectively generate new tissue.ResultsHerein, 3D printing-based strategy via the cryo-printing technology was employed to fabricate customized polyurethane (PU) porous scaffolds that mimic native meniscus. In order to enhance scaffold bioactivity for human mesenchymal stem cells (hMSCs) culture, scaffold surface modification through the physical absorption of collagen I and fibronectin (FN) were investigated by cell live/dead staining and cell viability assays. The results indicated that coating with fibronectin outperformed coating with collagen I in promoting multiple-aspect stem cell functions, and fibronectin favors long-term culture required for chondrogenesis on scaffolds. In situ chondrogenic differentiation of hMSCs resulted in a time-dependent upregulation of SOX9 and extracellular matrix (ECM) assessed by qRT-PCR analysis, and enhanced deposition of collagen II and aggrecan confirmed by immunostaining and western blot analysis. Gene expression data also revealed 3D porous scaffolds coupled with surface functionalization greatly facilitated chondrogenesis of hMSCs. In addition, the subcutaneous implantation of 3D porous PU scaffolds on SD rats did not induce local inflammation and integrated well with surrounding tissues, suggesting good in vivo biocompatibility.ConclusionsOverall, this study presents an approach to fabricate biocompatible meniscus constructs that not only recapitulate the architecture and mechanical property of native meniscus, but also have desired bioactivity for hMSCs culture and cartilage regeneration. The generated 3D meniscus-mimicking scaffolds incorporated with hMSCs offer great promise in tissue engineering strategies for meniscus regeneration.Graphical

Cultivation of hierarchical 3D scaffolds inside a perfusion bioreactor: scaffold design and finite-element analysis of fluid flow

The use of porous 3D scaffolds for the repair of bone nonunion and osteoporotic bone is currently an area of great interest. Using a combination of thermally-induced phase separation (TIPS) and 3D-plotting (3DP), we have generated hierarchical 3DP/TIPS scaffolds made of poly(lactic-co-glycolic acid) (PLGA) and nanohydroxyapatite (nHA). A full factorial design of experiments was conducted, in which the PLGA and nHA compositions were varied between 6‒12% w/v and 10‒40% w/w, respectively, totaling 16 scaffold formulations with an overall porosity ranging between 87%‒93%. These formulations included an optimal scaffold design identified in our previous study. The internal structures of the scaffolds were examined using scanning electron microscopy and microcomputed tomography. Our optimal scaffold was seeded with MC3T3-E1 murine preosteoblastic cells and subjected to cell culture inside a tissue culture dish and a perfusion bioreactor. The results were compared to those of a commercial CellCeram™ scaffold with a composition of 40% β-tricalcium phosphate and 60% hydroxyapatite (β-TCP/HA). Media flow within the macrochannels of 3DP/TIPS scaffolds was modeled in COMSOL software in order to fine tune the wall shear stress. CyQUANT DNA assay was performed to assess cell proliferation. The normalized number of cells for the optimal scaffold was more than twofold that of CellCeram™ scaffold after two weeks of culture inside the bioreactor. Despite the substantial variability in the results, the observed improvement in cell proliferation upon culture inside the perfusion bioreactor (vs. static culture) demonstrated the role of macrochannels in making the 3DP/TIPS scaffolds a promising candidate for scaffold-based tissue engineering.

Atomic layer deposition of zinc oxide onto 3D porous iron scaffolds for bone repair: in vitro degradation, antibacterial activity and cytocompatibility evaluation

Atomic layer deposition of zinc oxide onto 3D porous iron scaffolds for bone repair: in vitro degradation, antibacterial activity and cytocompatibility evaluation

Sustained Release of VEGF to Promote Angiogenesis and Osteointegration of Three-Dimensional Printed Biomimetic Titanium Alloy Implants.

Tumor resection and treatment of trauma-related regional large bone defects have major challenges in the field of orthopedics. Scaffolds that treat bone defects are the focus of bone tissue engineering. 3D printing porous titanium alloy scaffolds, prepared via electron beam melting technology, possess customized structure and strength. The addition of a growth factor coating to the scaffold introduces a specific form of biological activation. Vascular endothelial growth factor (VEGF) is key to angiogenesis and osteogenesis in vivo. We designed a porous titanium alloy scaffold/thermosensitive collagen hydrogel system, equipped with VEGF, to promote local osseointegration and angiogenesis. We also verified the VEGF release via thermosensitive collagen and proliferation and induction of the human umbilical vein endothelial cells (HUVECs) via the composite system in vitro. In vivo, using microscopic computed tomography (Micro-CT), histology, and immunohistochemistry analysis, we confirmed that the composite scaffold aids in angiogenesis-mediated bone regeneration, and promotes significantly more bone integration. We also discovered that the composite scaffold has excellent biocompatibility, provides bioactive VEGF for angiogenesis and osteointegration, and provides an important theoretical basis for the restoration of local blood supply and strengthening of bone integration.