Fabrication Of 3D Scaffolds Research Articles

Highly Bioadaptive Scaffolds with Tuned Porous Structure Templated by Xylan Nanocrystal High Internal Phase Pickering Emulsions.

Fabrication of traditional 3D cell culturing scaffolds requires synthetic polymers or additives, posing a risk of poor biocompatibility and low biodegradability. Pickering emulsions stabilized by biobased nanomaterials can be used as templates to produce scaffolds with facile tunable porous structure, excellent cytocompatibility, and biodegradability. In this study, very stable high internal phase Pickering emulsions (HIPPE) with an oil content of 80% were successfully prepared by xylan hydrate nanocrystals (XNC). The HIPPE can exist stably for more than 30 days, exhibiting a high viscosity. By adding cellulose nanofibers (CNF) and removing the oil phase, scaffolds with a tuned porous structure and enhanced cell culturing ability were successfully fabricated. In the HIPPE templated scaffolds with XNC/CNF, XNC plays a major role in stabilizing the emulsions, while CNF improves the mechanical properties of the scaffolds, both of which are vital to the successful fabrication of the scaffolds. Compared with non-HIPPE templated scaffolds, the HIPPE templated scaffold had a higher porosity and a higher median pore size. The HIPPE templated scaffold was able to maintain 80% cell activity and showed an excellent cytocompatibility. The HIPPE templated scaffolds consisting of XNC and CNF demonstrate great potential in 3D cell culturing for medical purpose.

Development of a five-axis printer for the fabrication of hybrid 3D scaffolds: From soft to hard phases and planar to curved surfaces

Three-dimensional (3D) printing of hybrid scaffolds with material gradients, combining soft and hard phases, is an appealing frontier in additive manufacturing. However, most 3D printers are limited to either three-axis or mono-material capabilities, rendering them unsuitable for fabricating hybrid scaffolds. Additionally, printing on curved surfaces requires advanced printing capabilities. Our work aims to advance additive manufacturing by developing a hybrid piezoelectric inkjet-extrusion printer equipped with five-axis functionalities. The printer could be used to fabricate customized hybrid scaffolds, surpassing conventional mono-material or linear three-axis printing strategies. The soft phase comprises a low-viscosity photocurable resin and a high-viscosity peptide hydrogel, while the hard phase comprises 3D-printed polylactic acid and hydroxyapatite parts. To validate the system, we fabricated three hybrid scaffolding use cases, characterized by multi-material porous structures fabricated on planar, single-curved, and free-form surfaces. The scaffolds were subsequently analyzed using digital microscopy to assess their accuracy, particularly the feature sizes of pores and struts (i.e., 0.8–3.6 mm). In the first part of the study, we demonstrated the versatility of inkjet and extrusion printing by hybrid printing an interconnected network in the soft phase on top of a planar ceramic hard phase. A pore width and height deviation of 6% was achieved compared to the intended design. In the second part of the study, we evaluated the 3D inkjet printing of a multi-material porous scaffold on a single-curved surface for osteochondral defects. The circumferential pore width and radial pore height deviated by 0.8% and 2%, respectively. Finally, we inkjet-printed a mesh structure on a free-form surface, which acted as a membrane for palatal implants. In this case, the pore width deviations were -16% in the printing direction and 2% perpendicular to the printing direction.

Fused Deposition Modeling 3D-Printed Scaffolds for Bone Tissue Engineering Applications: A Review.

The emergence of bone tissue engineering as a trend in regenerative medicine is forcing scientists to create highly functional materials and scaffold construction techniques. Bone tissue engineering uses 3D bio-printed scaffolds that allow and stimulate the attachment and proliferation of osteoinductive cells on their surfaces. Bone grafting is necessary to expedite the patient's condition because the natural healing process of bones is slow. Fused deposition modeling (FDM) is therefore suggested as a technique for the production process due to its simplicity, ability to create intricate components and movable forms, and low running costs. 3D-printed scaffolds can repair bone defects in vivo and in vitro. For 3D printing, variousmaterials including metals, polymers, and ceramics are often employed but polymeric biofilaments are promising candidates for replacing non-biodegradable materials due to their adaptabilityand environment friendliness. This review paper majorly focuses on the fused deposition modeling approach for the fabrication of 3D scaffolds. In addition, it also provides information on biofilaments used in FDM 3D printing, applications, and commercial aspects of scaffolds in bone tissue engineering.

3D printing of recombinant collagen/chitosan methacrylate/nanoclay hydrogels loaded with Kartogenin nanoparticles for cartilage regeneration.

Cartilage defects are frequently caused by trauma, illness and degradation of the cartilage. If these defects are not sufficiently treated, the joints will degrade irreversibly, possibly resulting in disability. Articular cartilage lacks blood vessels and nerves and is unable to regenerate itself, so the repair of cartilage defects is extremely challenging in clinical treatment. Tissue engineering technology is an emerging technology in cartilage repair and cartilage regeneration. 3D-printed hydrogels show great potential in cartilage tissue engineering for the fabrication of 3D cell culture scaffolds to mimic extracellular matrix. In this study, we construct a 3D-printed hydrogel loaded with nanoparticles by electrostatic interaction and photo cross-linking for the regeneration of cartilage, which has adaptable and drug-continuous release behavior. A photopolymerizable bioink was prepared using recombinant collagen, chitosan, nanoclay Laponite-XLG and nanoparticles loaded with Kartogenin (KGN). This bioink was added with KGN, a small molecule drug that promotes cartilage differentiation, and as a result, the 3D-printed CF/CM/3%LAP/KGN scaffolds obtained by extrusion printing is expected to be used for cartilage repair. It was shown that the 3D-printed scaffolds had good cytocompatibility for human bone marrow mesenchymal stem cells (hBMSCs) and exhibited excellent antimicrobial properties, the continuous release of KGN in the scaffold induced the hBMSCs differentiation into chondrocytes, which significantly enhanced the expression of collagen II and glycosaminoglycan. In vivo studies have shown that implantation of KGN-loaded scaffolds into cartilage-injured tissues promoted cartilage tissue regeneration. This study demonstrated that 3D-printed CF/CM/3%LAP/KGN scaffolds can be used for cartilage repair, which is expected to lead to new healing opportunities for cartilage injury-based diseases.

Impact of aging on the sintering behavior of bioactive-glass powder

Bioactive glasses (BGs) have been successfully used for several years as bone graft substitutes to fill defects and augment bone structures in orthopedic and dental procedures. Despite recent advances in the fabrication of reliable 3D scaffolds based on BG, the reproducibility of fabrication has only been marginally addressed and remains a challenge for their application. Recent studies have shown that BGs can react with moisture and atmospheric CO2 to form carbonates, affecting the properties and structure of the final product. In this study, factors that can affect the sintering behavior of BG powders were identified and investigated. A statistical analysis was then performed to optimize the BG sintering process, which revealed the possibility of obtaining BG scaffolds with reproducible density by acting on controllable factors such as aging and drying. In practice, this can be achieved by controlling the atmosphere during processing, handling, and storage of the material.

Fabrication Procedure for a 3D Hollow Nanofibrous Bifurcated-Tubular Scaffold by Conformal Electrospinning

Electrospinning has shown great potential for the fabrication of 3D nanofibrous tubular scaffolds for bifurcated vascular grafts. However, fabrication of complex 3D nanofibrous tubular scaffolds with bifurcated or patient-specific shapes remains limited. In this study, a 3D hollow nanofibrous bifurcated-tubular scaffold was fabricated by the uniform and conformal deposition of electrospun nanofibers via conformal electrospinning. By conformal electrospinning, electrospun nanofibers are conformally deposited onto a complex shape, such as the bifurcated region, without large pores or defects. Owing to conformal electrospinning, a corner profile fidelity (FC), a measure of conformal deposition of electrospun nanofibers at the bifurcated region, was increased 4 times at the bifurcation angle (θB) of 60°, and all FC values of the scaffolds reached 100%, regardless of the θB. Furthermore, the thickness of the scaffolds could be controlled by varying the electrospinning time. Leakage-free liquid transfer was successfully achieved owing to the uniform and conformal deposition of electrospun nanofibers. Finally, the cytocompatibility and 3D mesh-based modeling of the scaffolds were demonstrated. Thus, conformal electrospinning can be used to fabricate leakage-free and complex 3D nanofibrous scaffolds for bifurcated vascular grafts.

Three-Dimensional Biomaterials with Spatiotemporal Control for Regenerative Tissue Engineering.

At Morehouse College, one of the nation's top liberal arts historically black colleges and universities (HBCU) for African American men, research experiences are used to enhance the liberal arts educational experience. Securing research funding to train HBCU students is highly competitive and challenging due to the review process that is typically vetted by scientists from research-intensive universities who may not be familiar with the HBCU enterprise that may be comprised of insolvent infrastructures. In this Account, the synthesis and preparation of synthetic polymeric biomaterials that are used to facilitate or support changes in biological processes, enhance mechanical properties, and foster tissue growth in three dimensions (3D) under disease conditions will be discussed. The use of biomaterials to help control biological processes in disease states is limited. Hence, the fabrication of 3D scaffolds with chemical variability to grow or repair damaged tissues by inhibiting molecular pathways shows promise by controlling the cellular response to recapitulate 3D tissues and organs. The Mendenhall laboratory at Morehouse College uses 3D biomaterials to solve biological problems by probing cellular mechanistic pathways using natural products and nanoparticles. Toward this end, we have fabricated and manufactured 3D biomaterial scaffolds using chemical strategies to mitigate biological processes to help restore pristine tissue properties. Hydrogels are 3D polymeric matrixes that swell in aqueous environments and support cell growth that later infuriates the 3D matrix to create new tissue(s). In contrast, electrospun fibers use high electric fields to create porous 3D polymeric structures that can be used to create 3D tissue molds.The synergistic use of 3D biomaterial templates that can inhibit cellular damage while providing a mechanically strong scaffold to support regenerative tissue growth is essential to creating the next generation of biomaterials. This approach will require foresight using tools from synthetic biology, molecular biology, autonomous processes, advanced biomanufacturing, and machine learning (ML). The use of several biomaterials has been explored by the Mendenhall laboratory to design, prepare, fabricate, characterize, and evaluate 3D electrospun fibers and hydrogels containing hybrid compositions of polylactic acid (PLA), poly(n-vinylcaprolactam) (PVCL), cellulose acetate (CA), and methacrylated hyaluronic acid (meHA). This work contributed to the newly fabricated PVCL-CA fibers with morphological changes and nanoscale fiber hydrophobic surface properties. While the use of electrospun fibers can create hierarchal scaffolds for bone tissue engineering, the use of injectable gels for nonporous tissues such as articular cartilage presents another compelling biomaterial challenge. Using graft polymerization, we prepared PVLC-graft-HA and studied the effect of lower critical solution temperatures (LCSTs), gelation temperatures, and mechanical properties using temperature-controlled rheology. Additionally, we reported that articular cartilage (chondrocyte) cells seeded in PVCL-g-HA gels and incubated at hypoxia 1% O2 produced a 10-fold increase in extracellular matrix proteins (collagen) after 10 days. This work supported exploring new approaches to protecting chondrocyte cells under hypoxia using a 3D scaffold technology.

Dynamic Alginate Hydrogel as an Antioxidative Bioink for Bioprinting.

3D bioprinting holds great potential for use in tissue engineering to treat degenerative joint disorders, such as osteoarthritis. However, there is a lack of multifunctional bioinks that can not only support cell growth and differentiation, but also offer protection to cells against injuries caused by the elevated oxidative stress; this conditions is a common characteristic of the microenvironment of the osteoarthritis disease. To mitigate oxidative stress-induced cellular phenotype change and malfunction, an anti-oxidative bioink derived from an alginate dynamic hydrogel was developed in this study. The alginate dynamic hydrogel gelated quickly via the dynamic covalent bond between the phenylboronic acid modified alginate (Alg-PBA) and poly (vinyl alcohol) (PVA). It presented good self-healing and shear-thinning abilities because of the dynamic feature. The dynamic hydrogel supported long-term growth of mouse fibroblasts after stabilization with a secondary ionic crosslinking between introduced calcium ions and the carboxylate group in the alginate backbone. In addition, the dynamic hydrogel showed good printability, resulting in the fabrication of scaffolds with cylindrical and grid structures with good structural fidelity. Encapsulated mouse chondrocytes maintained high viability for at least 7 days in the bioprinted hydrogel after ionic crosslinking. Most importantly, in vitro studies implied that the bioprinted scaffold could reduce the intracellular oxidative stress for embedded chondrocytes under H2O2 exposure; it could also protect the chondrocytes from H2O2-induced downregulation of extracellular matrix (ECM) relevant anabolic genes (ACAN and COL2) and upregulation of a catabolic gene (MMP13). In summary, the results suggest that the dynamic alginate hydrogel can be applied as a versatile bioink for the fabrication of 3D bioprinted scaffolds with an innate antioxidative ability; this technique is expected to improve the regenerative efficacy of cartilage tissues for the treatment of joint disorders.

Novel Airflow-Field-Driven Melt Spinning 3D Printing of Tubular Scaffolds Based on Polycaprolactone Blends

The fabrication of various 3D tissue engineering tubular scaffolds with fibrous structures, to assist the human body in rapidly repairing a variety of ailments, is receiving more and more attention. Due to the inefficiency of the majority of fibrous preparation techniques, the question of how to rapidly produce the requisite three-dimensional tubular microfiber scaffold structures has become an urgent problem. In this study, an efficient polymer fiber preparation method was developed, using a high-speed airflow drive. Melt blending of polycaprolactone (PCL), polylactic acid (PLA), and tributyl citrate (TBC), was used for the printing material, to achieve the efficient preparation of tubular microfiber scaffolds with different structures. The scaffold diameter was as small as 2 mm, the wall thickness was up to 100 μm, and the fiber injection efficiency reached 15.48 g/h. By utilizing simulations to optimize the printing parameters and by adjusting the printing settings, it was possible to achieve a controlled fiber diameter in the range of 3 μm to 15 μm. In addition, plasma treatment was applied to the microfibers' surface, to increase their wettability, and the efficiency of the hydrophilic modification was demonstrated. Furthermore, the mechanical property test demonstrated that the fibers have a tensile strength of 1.36 ± 0.16 MPa and a tensile strain of 30.8 ± 3.5%. The radial compressive strain of the tubular scaffold could reach 60% of the original scaffold's diameter. Finally, the in vitro degradation of the fibers at various pH values was tested. The results showed that, under alkaline conditions, the surface of the fibers would be severely crushed and the rate of deterioration would increase.

Fabrication of 3D Bioprinted Bi-Phasic Scaffold for Bone-Cartilage Interface Regeneration.

Treatments for osteochondral defects (OCDs) are mainly palliative and, with the increase in this pathology seen among both young and elderly people, an alternative treatment modality is sought. Many tissue-engineered strategies have been explored for regenerating the cartilage-bone interface; however, they generally fall short of being ideal. Although cell-laden hydrogel scaffolds are a common approach for bone and cartilage tissue regeneration, they usually lack homogenous cell dispersion and patient specificity. In this study, a biphasic 3D bioprinted composite scaffold was fabricated for cartilage-bone interface regeneration. To overcome the shortcoming of both materials, alginate-gelatin (A-G) hydrogel was used to confer a naturally occurring environment for the cells and polycaprolactone (PCL) was used to enhance mechanical stability, thus maximizing the overall performance. Hydroxyapatite fillers were added to the PCL in the bone phase of the scaffold to improve its bioactivity. Physical and biological evaluation of scaffolds in both phases was assessed. The scaffolds demonstrated a desirable biological response both singly and in the combined PCL/A-G scaffolds, in both the short term and longer term, showing promise as an interfacial material between cartilage and bone.

A Review of 3D Polymeric Scaffolds for Bone Tissue Engineering: Principles, Fabrication Techniques, Immunomodulatory Roles, and Challenges.

Over the last few years, biopolymers have attracted great interest in tissue engineering and regenerative medicine due to the great diversity of their chemical, mechanical, and physical properties for the fabrication of 3D scaffolds. This review is devoted to recent advances in synthetic and natural polymeric 3D scaffolds for bone tissue engineering (BTE) and regenerative therapies. The review comprehensively discusses the implications of biological macromolecules, structure, and composition of polymeric scaffolds used in BTE. Various approaches to fabricating 3D BTE scaffolds are discussed, including solvent casting and particle leaching, freeze-drying, thermally induced phase separation, gas foaming, electrospinning, and sol-gel techniques. Rapid prototyping technologies such as stereolithography, fused deposition modeling, selective laser sintering, and 3D bioprinting are also covered. The immunomodulatory roles of polymeric scaffolds utilized for BTE applications are discussed. In addition, the features and challenges of 3D polymer scaffolds fabricated using advanced additive manufacturing technologies (rapid prototyping) are addressed and compared to conventional subtractive manufacturing techniques. Finally, the challenges of applying scaffold-based BTE treatments in practice are discussed in-depth.

Fabrication and characterization of ceramic-polymer composite 3D scaffolds and demonstration of osteoinductive propensity with gingival mesenchymal stem cells.

The fabrication of biomaterial 3D scaffolds for bone tissue engineering applications involves the usage of metals, polymers, and ceramics as the base constituents. Notwithstanding, the composite materials facilitating enhanced osteogenic differentiation/regeneration are endorsed as the ideally suited bone grafts for addressing critical-sized bone defects. Here, we report the successful fabrication of 3D composite scaffolds mimicking the ECM of bone tissue by using ∼30 wt% of collagen type I (Col-I) and ∼70 wt% of different crystalline phases of calcium phosphate (CP) nanomaterials [hydroxyapatite (HAp), beta-tricalcium phosphate (βTCP), biphasic hydroxyapatite (βTCP-HAp or BCP)], where pH served as the sole variable for obtaining these CP phases. The different Ca/P ratio and CP nanomaterials orientation in these CP/Col-I composite scaffolds not only altered the microstructure, surface area, porosity with randomly oriented interconnected pores (80-450 μm) and mechanical strength similar to trabecular bone but also consecutively influenced the bioactivity, biocompatibility, and osteogenic differentiation potential of gingival-derived mesenchymal stem cells (gMSCs). In fact, BCP/Col-I, as determined from micro-CT analysis, achieved the highest surface area (∼42.6 m2 g-1) and porosity (∼85%), demonstrated improved bioactivity and biocompatibility and promoted maximum osteogenic differentiation of gMSCs among the three. Interestingly, the released Ca2+ ions, as low as 3 mM, from these scaffolds could also facilitate the osteogenic differentiation of gMSCs without even subjecting them to osteoinduction, thereby attesting these CP/Col-I 3D scaffolds as ideally suited bone graft materials.

Click chemistry for 3D bioprinting.

Bioinks are employed in the fabrication of 3D scaffolds containing cells and macromolecules that can be applied in regenerative medicine. The use of such bioinks facilitates the controlled introduction and localization of macromolecules, bioactives and cells for the biofabrication of living tissues. To enable the successful preparation of the bioinks, strategies involving the use of so-called cross linkers, which may be ionic, chemical, photo-etc. based, are employed. Some of these strategies such as the use of glutaraldehyde as a crosslinker or harsh crosslinking conditions may however compromise the cytocompatibility of the bioink. To circumvent this challenge, the employment of click chemistry technology has been proposed. This is because, click chemistry can enable the preparation of well-tuned bioinks in the absence of problematic cross-linkers, while ensuring that favorable gelation rate, degradation rate, and cell viability properties of the bioinks are not compromised. Indeed, the bio-orthogonal nature of click chemistry has been suggested to enhance the maintenance of high cell viability in scaffolds. In this regard, the current study explored the potential of using different click chemistries in specific bioprinting techniques. Major bioinks produced using click chemistry were also identified, with existing challenges and future trends discussed. It is anticipated that this review will be invaluable to the tissue engineering field by providing an important resource for bioengineers and a basis of future decisions regarding the selection of the preferred click chemistry for specific bioink functionalities.

3D-Printed Tubular Scaffolds Decorated with Air-Jet-Spun Fibers for Bone Tissue Applications.

The fabrication of instructive materials to engineer bone substitute scaffolds is still a relevant challenge. Current advances in additive manufacturing techniques make possible the fabrication of 3D scaffolds with even more controlled architecture at micro- and submicrometric levels, satisfying the relevant biological and mechanical requirements for tissue engineering. In this view, integrated use of additive manufacturing techniques is proposed, by combining 3D printing and air-jet spinning techniques, to optimize the fabrication of PLA tubes with nanostructured fibrous coatings for long bone defects. The physicochemical characterization of the 3D tubular scaffolds was performed by scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry, profilometry, and mechanical properties. In vitro biocompatibility was evaluated in terms of cell adhesion, proliferation, and cell–material interactions, by using human fetal osteoblasts to validate their use as a bone growth guide. The results showed that 3D-printed scaffolds provide a 3D architecture with highly reproducible properties in terms of mechanical and thermal properties. Moreover, nanofibers are collected onto the surface, which allows forming an intricate and interconnected network that provides microretentive cues able to improve adhesion and cell growth response. Therefore, the proposed approach could be suggested to design innovative scaffolds with improved interface properties to support regeneration mechanisms in long bone treatment.

Digital light processing-based 3D bioprinting of κ-carrageenan hydrogels for engineering cell-loaded tissue scaffolds

The demand to regenerate biological tissues and organs in patients as an alternative to transplants has motivated the tissue engineering field. Digital light processing (DLP)-based three-dimensional (3D) bioprinting technology enables the rapid fabrication of complex 3D cell-laden scaffolds for tissue engineering applications. Herein, we demonstrate the outstanding printability of photocurable methacrylate-κ-carrageenan (MA-κ-CA) using DLP 3D printing. 3D printed hydrogels with varying concentrations (1–5% w/v) of MA-κ-CA were thoroughly characterized for their swelling, degradation, mechanical, and rheological properties, and suitability for bioprinting with living cells. Viscosity and shear thinning behavior of MA-κ-CA faithfully recapitulate the biomechanical properties of soft human tissues. Encapsulated NIH-3T3 cells show high viability and good proliferation over several days. Furthermore, highly complex 3D hydrogel scaffolds of MA-κ-CA were printed to recapitulate the biological complexity of tissues and organs. This work presents a polysaccharide bioink for preparing tissue scaffolds by DLP 3D bioprinting.

Fabrication of 3D scaffolds based on fully biobased unsaturated polyester resins by microstereo-lithography

Additive Manufacturing (AM) technologies are an effective route to fabricate tailor made scaffolds for tissue engineering (TE) and regenerative medicine, with microstereo-lithography (µSLA) being one of the most promising techniques to produce high quality 3D structures. Here, we report the crosslinking studies of fully biobased unsaturated polyesters (UPs) with 2-hydroxyethyl methacrylate (HEMA) as the unsaturated monomer (UM), using thermal and µSLA crosslinking processes. The resulting resins were fully characterized in terms of their thermal and mechanical properties. Determination of gel content, water contact angle, topography and morphology analysis by atomic force microscopy and scanning electron microscopy were also performed. The results show that the developed UP resins (UPRs) have promising properties for µSLA. In vitro cytotoxicity assays performed with 3T3-L1 cell lines showed that the untreated scaffolds exhibited a maximum cellular viability around 60%, which was attributed to the acidic nature of the UPRs. The treatment of the UPRs and scaffolds with ethanol (EtOH) improved the cellular viability to 100%. The data presented in this manuscript contribute to improve the performance of biobased UPs in AM.

Recent advances of natural biopolymeric culture scaffold: synthesis and modification

ABSTRACT Traditionally existing 2D culture scaffold has been inappropriately validated due to the failure in generating the precise therapeutic response. Therefore, this leads to the fabrication of 3D culture scaffold resolving the limitations in the in vivo environment. In recent years, tissue engineering played an important role in the field of bio-medical engineering. Biopolymer material, a novel natural material with excellent properties of nontoxic and biodegradable merits can be served as culture scaffold. This review summarizes the modifications of natural biopolymeric culture scaffold with different crosslinkers and their application. In addition, this review provides the recent progress of natural biopolymeric culture scaffold mainly focusing on their properties, synthesizing and modification and application.

Fabrication of Piezoelectric Electrospun Termite Nest-like 3D Scaffolds for Tissue Engineering.

A high piezoelectric coefficient polymer and biomaterial for bone tissue engineering— poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP)—has been successfully fabricated into 3D scaffolds using the wet electrospinning method. Three-dimensional (3D) scaffolds have significant advantages for tissue engineering applications. Electrospinning is an advanced method and can fabricate 3D scaffolds. However, it has some limitations and is difficult to fabricate nanofibers into 3D shapes because of the low controllability of porosity and internal pore shape. The PVDF-HFP powders were dissolved in a mixture of acetone and dimethylformamide with a ratio of 1:1 at various concentrations of 10, 13, 15, 17, and 20 wt%. However, only the solutions at 15 and 17 wt% with optimized electrospinning parameters can be fabricated into biomimetic 3D shapes. The produced PVDF-HFP 3D scaffolds are in the cm size range and mimic the structure of the natural nests of termites of the genus Apicotermes. In addition, the 3D nanofiber-based structure can also generate more electrical signals than the conventional 2D ones, as the third dimension provides more compression. The cell interaction with the 3D nanofibers scaffold was investigated. The in vitro results demonstrated that the NIH 3T3 cells could attach and migrate in the 3D structures. While conventional electrospinning yields 2D (flat) structures, our bio-inspired electrospun termite nest-like 3D scaffolds are better suited for tissue engineering applications since they can potentially mimic native tissues as they have biomimetic structure, piezoelectric, and biological properties.

Three-dimensional (3D), macroporous, elastic, and biodegradable nanocomposite scaffold for in situ bone regeneration: Toward structural, biophysical, and biochemical cues integration

Although bone tissue with remarkable healing capabilities, the rapid and successful bone regeneration continues to present a challenge because that the influence factors for bone healing are multifaceted, especially for massive bone defects. From a cell/material interactions point of view, integrating multiple cues into one biomaterial is considered as a promising approach in the clinical treatment of bone defects thanks to the provided multiple stimuli. Herein, 3D macroporously elastic biodegradable nanocomposite bone scaffolds (PCSG) were successfully developed based on poly(citrate-siloxane) (PCS) hybrid elastomer and reduced graphene oxide (rGO). The PCSG scaffolds combine with structure (3D, largely open and interconnected pore architecture, high porosity), biophysics (high mechanical properties, roughness surface, piezoelectricity property), and biochemistry cues (silica cross-linked network, Si ions release). Experiments demonstrate that the structurally, biophysically, and biochemically biomimetic properties of PCSG scaffolds are beneficial for triggering cell adhesion, proliferation, matrix mineralization , osteogenic differentiation of osteoblasts (MC3T3-E1) in vitro and significantly promoting in situ bone regeneration in a calvarial bone defect model. The effective and simple strategy of multiple cues integration could pave a universally applicable way in development of bone tissue engineering biomaterials with good osteoinductivity and osteoconductivity for large defects repair, and the reported PCSG scaffolds demonstrate the potential clinic application in fields of bone regeneration and 3D culture of cells. • Integrating structure, biophysics, and biochemistry cues into one bone scaffold for in situ bone regeneration. • The fabrication of 3D bone scaffold with largely open and porosity via the facile sol-gel method. • The proposed bone scaffolds with super Young's modulus not only in dry state but in hydrated condition.

The Application of Polycaprolactone in Three-Dimensional Printing Scaffolds for Bone Tissue Engineering.

Bone tissue engineering commonly encompasses the use of three-dimensional (3D) scaffolds to provide a suitable microenvironment for the propagation of cells to regenerate damaged tissues or organs. 3D printing technology has been extensively applied to allow direct 3D scaffolds manufacturing. Polycaprolactone (PCL) has been widely used in the fabrication of 3D scaffolds in the field of bone tissue engineering due to its advantages such as good biocompatibility, slow degradation rate, the less acidic breakdown products in comparison to other polyesters, and the potential for loadbearing applications. PCL can be blended with a variety of polymers and hydrogels to improve its properties or to introduce new PCL-based composites. This paper describes the PCL used in developing state of the art of scaffolds for bone tissue engineering. In this review, we provide an overview of the 3D printing techniques for the fabrication of PCL-based composite scaffolds and recent studies on applications in different clinical situations. For instance, PCL-based composite scaffolds were used as an implant surgical guide in dental treatment. Furthermore, future trend and potential clinical translations will be discussed.