3D Bioplotter Research Papers

Bulk Ni samples were additively manufactured using particle-based ink extrusion. Three samples were characterized for thermoelectric transport properties including electrical resistivity, thermal conductivity, Seebeck coefficient, and thermoelectric figure of merit. Sample-to-sample deviations in transport were small but observable; these were attributed to stochastic porosity from the manufacturing method. Transport results were compared to previously published results in both porous and dense Ni, indicating that the salient features in the traditionally manufactured Ni samples are maintained in their additively manufactured counterparts. These results are offered as evidence of the feasibility of using particle-based ink extrusion additive manufacturing for thermoelectric applications.

Decellularized extracellular matrices (ECMs) are being extensively used for tissue engineering purposes and detergents are predominantly used for this. A facile detergent-free decellularization method is developed for dermal matrix and compared it with the most used detergent-based decellularization methods. An optimized, single-step, cost-effective Hypotonic/Hypertonic (H/H) Sodium Chloride (NaCl) solutions-based method is employed to decellularize goat skin that resulted in much higher yield than other methods. The ECM composition, mechanical property, and cytocompatibility are evaluated and compared with other decellularization methods. Furthermore, this H/H-treated decellularized dermal ECM (ddECM) exhibits a residual DNA content of <50 ng mg−1 of dry tissue. Moreover, 85.64 ± 3.01% of glycosaminoglycans…

Objective. The objective of this study was to compare the host inflammatory response of our previously described hyperelastic, 3D-printed (3DP) hydroxyapatite (HA)-demineralized bone matrix (DBM) composite scaffold to the response elicited with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a preclinical rat posterolateral lumbar fusion model. Summary of Background Data. Our group previously found that this 3D-printed HA-DBM composite material shows promise as a bone graft substitute in a preclinical rodent model, but its safety profile had yet to be assessed. Methods. Sixty female Sprague-Dawley rats underwent bilateral posterolateral intertransverse lumbar spinal fusion using with the following…

Microlattices with orthogonal 0-90° architecture are 3D-extrusion printed from inks containing a blend of oxide powders (Co3O4, CuO, Fe2O3, and NiO) and metal powder (Cr). Equiatomic CoCrCuFeNi microlattices with ∼170 µm diameter struts are then synthesized by H2-reduction of the oxides followed by sintering and interdiffusion of the resulting metals. These process steps are studied by in-situ synchrotron X-ray diffraction on single extruded microfilaments (lattice struts) with ∼250 µm diameter. After reduction and partial interdiffusion at 600 ˚C for 1 h under H2, filaments consist of lightly-sintered metallic particles with some unreduced Cr2O3. A reduced, nearly fully densified (porosity: 1.6 ± 0.7%)…

Polymer blend system has been commonly applied in a wide variety of applications. Herein, we propose to introduce sugar particles to polymer matrix, which results in a controllable polymer swelling under the action of osmotic pressure upon soaking in water. Taking advantage of this economic and environment-friendly, water-induced polymer swelling process, we have fabricated wrinkled conductive films and 3D structures by depositing conductive materials on the swollen polymer substrates for stretchable strain sensing devices. Several commercial silicone elastomers were utilized in the study. Key processing factors affecting the polymer swelling were investigated, including film thickness, sugar concentration, and temperature of…

As an engineering frontier, highly stretchable sensors are widely applied in many fields, such as human motion detection, personal healthcare monitoring, and human-machine interactions. In this study, novel silver nanowire (AgNW)-based stretchable sensors with hierarchical wrinkled structures were fabricated through a two-step process, namely water-induced swelling and AgNW deposition. As highly soluble additives, sodium chloride particles were incorporated into the elastomer matrix. Upon soaking in dopamine aqueous solution, significant swelling was introduced onto the elastomer substrate. The dopamine deposition is accompanied with the swelling process, which endows the sample surface with ultra-hydrophilicity. Additionally, the dopamine-modified swollen samples “capture” the nanowires…

Polyelectrolyte complex (PEC) hydrogels are advantageous as therapeutic agent and cell carriers. However, due to the weak nature of physical crosslinking, PEC swelling and cargo burst release are easily initiated. Also, most current cell-laden PEC hydrogels are limited to fibers and microcapsules with unfavorable dimensions and structures for practical implantations. To overcome these drawbacks, alginate (Alg)/poly-L-ornithine (PLO) PEC hydrogels are fabricated into microcapsules, fibers, and bulk scaffolds to explore their feasibility as drug and cell carriers. Stable Alg/PLO microcapsules with controllable shapes are obtained through aqueous electrospraying technique, which avoids osmotic shock and prolongs the release time. Model enzyme and…

Poly (lactic-co-glycolic acid) (PLGA) is a star biodegradable polymer widely studied and applied in the biomedical field. Improving the acidic microenvironment caused by its degradation products and regulating its degradation behavior are still urgent scientific and technological problems to be solved. In this study, to regulate the degradation behaviors of PLGA and improve its bioactivity, hydroxyapatite (HA) and magnesium oxide (MgO) were incorporated into PLGA substrate in different proportions and a series of 3D-printing PLGA/HA/MgO (PHM) composite porous scaffolds were prepared. Then the physicochemical properties, degradation behaviors, in vitro and in vivo biological performance of fabricated scaffolds were systematically studied.…

4D printing of shape memory polymers (SMPs) endows the 3D printed structures with tunable shape-changing behavior and functionalities that opens up new avenues towards intelligent devices. Multiple-SMPs, specially, could memorize more than two shapes that have greatly extended the performance of 4D printed structures. However, the actuation to trigger the shape change of 4D printed multiple-SMPs is usually by direct heating to different temperatures. It hasn’t brought the full superiority of the programmability of multiple-SMPs with distinct responsive regions that could be sequentially and selectively actuated by various stimuli. Besides, the functionality of multi-material based additive manufacturing is another area…

Background Poly(3-caprolactone) (PCL)/β-tricalcium phosphate (β-TCP) composite scaffolds fabricated by three-dimensional (3D) printing are one of the common scaffolds for bone tissue regeneration. However, the main challenge of these 3D printed PCL/β-TCP scaffolds is the fact that many cells pass from porosities during in vitro cell seeding, leading to poor initial cell attachment. This study aimed to demonstrate the fabrication of a new collagen coating process for optimizing the hydrophilic property and cell-substrate interactions. This method may be used for coating collagen on any relevant biomedical constructs made of synthetic polymers to increase their biocompatibility and cell attachment. Materials and methods…

People with neurological deficits face difficulties perceiving their surroundings, resulting in an urgent need for wearable electronic skin (e-skin) that can monitor external stimuli and temperature changes. However, the monolithic structure of e-skin is not conducive to breathability and hinders hair growth, limiting its wearing comfort. In this work, we prepared fully three-dimensional (3D) printed e-skin that allowed hair penetration and growth. This e-skin also achieved simultaneous pressure and temperature detection and a high tactile resolution of 100 cm–2, which is close to that of human fingertips. The temperature sensor maintained linear measurements within 10–60 °C. The pore microstructure prepared…

Objectives There are complications in applying regenerative strategies at the interface of hard and soft tissues due to the limited designs of constructs that can accommodate different cell types in different sites. The problem originates from the challenges in the adhesion of dissimilar materials, such as polymers and hydrogels, that can be suitable for regenerating different tissues such as bone and soft tissues. This paper presents a design of a new hybrid construct in which a polymer (polycaprolactone (PCL)) membrane firmly adheres to a layer of hydrogen (gelatin). Methods PCL membranes with defined size and porosity were fabricated using 3D…

3D Bioprinting plays an irreplaceable role in bone tissue engineering. Shellac and curcumin are two natural compounds that are widely used in the food and pharmaceutical sectors. In this study, a new composite scaffold with good biocompatibility and antibacterial ability was manufactured by adding shellac and curcumin into the traditional bone scaffold through low-temperature three-dimensional printing (LT-3DP), and its impact on the osteoimmune microenvironment was evaluated.

The membrane based on receptor functionalization provides a new paradigm for the development of mechanical biosensors. However, improvement of sensitivity and test accuracy is still a challenge for mechanical biosensors in practical application. Herein, a surface stress mechanical biosensor (MBioS) based on double-side-gold nanoparticale (AuNP)-coated grid-type polydimethylsiloxane (PDMS) membrane (D-G-MBioS) and 3D printing for human serum albumin (HSA) detection is developed. The surface stress is amplified by the grid coupling sandwich immune structure to improve the sensitivity of the MbioS, successfully reducing limite of detection (LOD) by two orders of magnitude. By self-assembly of AuNPs, the double-side-coated PDMS membrane is…

High-density polyethylene (HDPE) is a promising material for the development of scaffold implants for auricle reconstruction. However, preparing a personalized HDPE auricle implant with favorable bioactive and antibacterial functions to promote skin tissue ingrowth is challenging. Herein, we present 3D-printed HDPE auricle scaffolds with satisfactory pore size and connectivity. The layer-by-layer (LBL) approach was applied to achieve the improved bioactive and antibacterial properties of these 3D printed scaffolds. The HDPE auricle scaffolds were fabricated using an extrusion 3D printing approach, and the individualized macrostructure and porous microstructure were both adjusted by the 3D printing parameters. The polydopamine (pDA) coating method…

Decellularized extracellular matrix hydrogel (dECM-G) has demonstrated its significant tissue-specificity, high biocompatibility, and versatile utilities in tissue engineering. However, the low mechanical stability and fast degradation are major drawbacks for its application in three-dimensional (3D) printing. Herein, we report a hybrid hydrogel system consisting of dECM-Gs and photocrosslinkable gelatin methacrylate (GelMA), which resulted in significantly improved printability and structural fidelity. These premixed hydrogels retained high bioactivity and tissue-specificity due to their containing dECM-Gs. More specifically, it was realized that the hydrogel containing dECM-G derived from porcine peripheral nerves (GelMA/pDNM-G) effectively facilitated neurite growth and Schwann cell migration from two-dimensional cultured…

Purpose Drug release from hypromellose-based tablets involves the formation of characteristic dry cores surrounded by outer gel layers in aqueous media. The aim of this study was to investigate the effect of perforation sizes on the dissolution of repaglinide from three-dimensionally (3D) printed tablets with two viscosity grades of hypromellose as rate-controlling polymer. Methods Printing pastes of appropriate consistency were developed and fed into a bioplotter cartridge to extrude strands/filaments. Tablets were printed in a crisscross pattern with 1.0, 1.3, and 1.6 mm of inter-strand distances. Printed tablets were characterized and repaglinide dissolution data were evaluated mathematically. Results Scanning electron…

Nonunion bone fractures can impact the quality of life and represent a major economic burden. Scaffold-based tissue engineering has shown promise as an alternative to bone grafting. Achieving desirable bone reconstruction requires appropriate surface properties, together with optimizing the internal architecture of 3D scaffolds. This study presents the surface modification of poly(lactic-co-glycolic acid) (PLGA), collagen, and PLGA-collagen via an argon plasma treatment. Argon plasma can modify the surface chemistry and topography of biomaterials and improve in vivo integration. Solvent-cast films were prepared using 1,1,1,3,3,3-hexafluoro-2-propanol and characterized via differential scanning calorimetry, thermogravimetric analysis, contact angle measurement, and critical surface tension analysis.…

With more than 1.5 million total knee and hip implants placed each year, there is an urgent need for a drug delivery system that can effectively support the repair of bone infections. Scaffolds made of natural biopolymers are widely used for this purpose due to their biocompatibility, biodegradability, and suitable mechanical properties. However, the poor processability is a bottleneck, as highly customizable scaffolds are desired. The aim of the present research is to develop a scaffold made of thermoplastic collagen (TC) using 3D printing technology. The viscosity of the material was measured using a rheometer. A 3D bioplotter was used…

The inevitable gap between in vitro and in vivo degradation rate of biomaterials has been a challenging factor in the optimal designing of scaffold’s degradation to be balanced with new tissue formation. To enable non-/minimum-invasive tracking of in vivo scaffold degradation, chemical modifications have been applied to label polymers with fluorescent dyes. However, the previous approaches may have limited expandability due to complicated synthesis processes. Here, we introduce a simple and efficient method to fluorescence labeling of polymeric scaffolds via blending with near-infrared (NIR) quantum dots (QDs), semiconductor nanocrystals with superior optical properties. QDs-labeled, 3D-printed PCL scaffolds showed promising efficiency…

Gelatin methacrylate (GelMA) is a widely used biomaterial in tissue engineering and regenerative medicine. GelMA is a chemically modified form of gelatin. Researchers have employed various methods to synthesize GelMA, such as the conventional method (Bulcke et al. 2000), the sequential method (Lee et al. 2015), and facile one-pot (Shirahama et al. 2016) methods to achieve GelMA hydrogels with a wide range of degree of functionalization or methacrylation. However, the impact of these different synthesis methods and their reac- tion parameters on GelMA hydrogels and scaffolds remains to be investigated concerning bioink formulation and 3D printing application. In this study,…

The poor interfacial adhesion between silk fiber and polyester species remains a critical problem for the optimal mechanical performance of silk-reinforced polyester composites. Here, we investigated in quantitative terms the interfacial properties between natural silk fibers and polycaprolactone (PCL) at nano-, micro-, and macroscales and fabricated continuous silk-PCL composite filaments by melt extrusion and drawing processing of PCL melt at 100, 120, and 140 °C. Bombyx mori (Bm) silk, Antheraea pernyi (Ap) silk, and polyamide6 (PA6) fiber were compared to the composite with PCL. The Ap silk exhibited the highest surface energy, the best wettability, and the largest interfacial shear…

Magnetic refrigeration is an energy-efficient, sustainable, environmentally-friendly alternative to the conventional vapor-compression cooling technology. There are several magnetic refrigerator device designs in existence today that are predicted to be highly energy-efficient, on condition that suitable working materials can be developed. This challenge in manufacturing magnetocaloric devices is unresolved, mainly due to issues related to shaping the mostly brittle magnetocaloric alloys into thin-walled channeled regenerator structures to facilitate efficient heat transfer between the solid refrigerant and the heat exchange fluid in an active magnetic regenerator (AMR) cooling device. To address this challenge, a novel extrusion-based additive manufacturing (AM) method has been…

Amine-functionalized polymers (AFPs) are able to react with carbon dioxide (CO2) and are therefore useful in CO2 capture and sensing. To develop AFP-based CO2 sensors, it is critical to examine their electrical responses to CO2 over long periods of time, so that the device can be used consistently for measuring CO2 concentration. To this end, we synthesized poly(N-[3-(dimethylamino)propyl] methacrylamide) (pDMAPMAm) by free radical polymerization and tested its ability to behave as a CO2-responsive polymer in a transducer. The electrical response of this polymer to CO2 upon long exposure times was measured in both the aqueous and solid phases. Direct current…

3D bioprinting technology has gained increased attention in the regenerative medicine and tissue engineering communities over the past decade with their attempts to create functional living tissues and organs de novo. While tissues such as skin, bone, and cartilage have been successfully fabricated using 3D bioprinting, there are still many technical and process driven challenges that must be overcome before a complete tissue engineered solution is realized. Although there may never be a single adopted bioprinting process in the scientific community, adherence to optimized bioprinting protocols could reduce variability and improve precision with the goal of ensuring high quality printed…

A modular design composed of 3D-printed polycaprolactone (PCL) as the load-bearing module, and dual porosity gelatin foam as the bio-reactive module, was developed and characterized in this study. Surface treatment of the PCL module through aminolysis-aldehyde process was found to yield a stronger interface bonding compared to NaOH hydrolysis, and therefore was used in the fabrication procedure. The modular scaffold was shown to significantly improve the mechanical properties of the gelatin foam. Both compressive modulus and ultimate strength was found to increase over 10 times when the modular design was employed. The bio-reactive module i.e., gelatin foam, presented a dual…

Postoperative restenosis in patients with external ear canal (EEC) atresia or stenosis is a common complication following canaloplasty. Our aim in this study was to explore the feasibility of using a three dimensionally (3D)-printed, patient-individualized, drug ((dexamethasone (DEX)), and ciprofloxacin (cipro))-releasing external ear canal implant (EECI) as a postoperative stent after canaloplasty. We designed and pre-clinically tested this novel implant for drug release (by high-performance liquid chromatography), biocompatibility (by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay), bio-efficacy (by the TNF-α (tumor necrosis factor-alpha)-reduction test (DEX) and inhibition zone test (for cipro)), and microbial contamination (formation of turbidity or sediments in culture medium).…

This work presents the first example of an imidazolium ionene containing aromatic ether-ketone-ether linkages inspired by poly(ether ether ketone) (PEEK), a well-known ultrahigh-performance (UHP) engineering polymer. The requisite starting materials for this “PEEK ionene” were efficiently synthesized in good yields and then polymerized through condensation (Menshutkin reaction), followed by anion metathesis to form the final polymer product, which had a number-average molecular weight (Mn) of ∼90 kDa. The properties of the PEEK-ionene were thoroughly characterized, and its potential utility was demonstrated by analyzing this material as a gas separation membrane and 3D-printing this ionic UHP polymer. Thin films of this…

Photoresponsive soft liquid crystalline elastomers (LCEs) transform light’s energy into dynamic shape changes and are considered promising candidates for production of soft robotic or muscle-like devices. 3D printing allows access to elaborated geometries as well as control of the photoactuated movements; however, this development is still in its infancy and only a limited choice of LCE is yet available. Herein, we propose to introduce biocompatible and sustainable cellulose nanocrystals (CNC) into an LCE in order to facilitate the printing process by direct ink writing (DIW) and to benefit from the anisotropic mechanical properties resulting from the extrusion-induced alignment of such…

Impedance-matched acoustic materials were developed to improve ultrasound penetration through the aberration layer. The traditional ultrasound layer matching material is called a couplant, which can only enhance ultrasound transmission to soft biological media such as the cartilage and muscle but cannot penetrate hard media such as the bone. Here, we propose a phase-modulated complementary acoustic metamaterial based on the principle of impedance matching, which enables ultrasound to penetrate the bone, and use the equivalent parameter technology of acoustic metamaterials for parameter design. Ultrasonic layer adjustment is performed through 3D printing and corrects bone aberrations. Several configurations were investigated through numerical…

Cultivated meat harnesses tissue engineering (TE) concepts to create sustainable, edible muscle tissues, for addressing the rising meat product demands and their global consequences. As 3D-printing is a promising method for creating thick and complex structures, two plant-protein-enriched scaffolding compositions were primarily assessed in our work as 3D-printable platforms for bovine satellite cells (BSC) maturation. Mixtures of pea protein isolate (PPI) and soy protein isolate (SPI) with RGD-modified alginate (Alginate(RGD)) were evaluated as prefabricated mold-based and 3D-printed scaffolds for BSC cultivation, and ultimately, as potential bioinks for cellular printing. Mold-based protein enriched scaffolds exhibited elevated stability and stiffness compared to…

Presented here is the synthesis of a 3D printable nano-polysaccharide self-healing hydrogel for flexible strain sensors. Consisting of three distinct yet complementary dynamic bonds, the crosslinked network comprises imine, hydrogen, and catecholato-metal coordination bonds. Self-healing of the hydrogel is demonstrated by macroscopic observation, rheological recovery, and compression measurements. The hydrogel was produced via imine formation of carboxyl methyl chitosan, oxidized cellulose nanofibers, and chitin nanofibers followed by two subsequent crosslinking stages: immersion in tannic acid (TA) solution to create hydrogen bonds, followed by soaking in FeIII solution to form catecholato-metal coordination bonds between TA and FeIII. The metal coordination bonds…

Bacterial infection is an important challenge when repairing bone defects with implant materials. The development of functional scaffolds with an intelligent antibacterial function that can be used for bone repair are of great significance. In this study, we used vancomycin (VAN) as a model antibiotic drug and proposed the fabrication of VAN-loaded zeolite imidazole framework-8-functionalized bioglass (ZIF-8@VAN@BG) scaffolds with a pH-responsive antibacterial effect for use in potentially infected bone repair applications. The physicochemical properties, in vitro biological properties and antibacterial properties of the scaffolds were studied. The results showed that the ZIF-8@VAN@BG scaffolds had a 3D porous structure and exhibited…

The lack of an effective printable ink preparation method and the usual mechanically weak performance obstruct the functional 3D printing hydrogel exploitation and application. Herein, we propose a gentle pre-cross-linking strategy to enable a loosely cross-linked cellulose network for simultaneously achieving favorable printability and a strong hydrogel network via mediating the cellulose self-assembly. A small amount of epichlorohydrin is applied to (i) slightly pre-cross-link the cellulose chains for forming the percolating network to regulate the rheological properties and (ii) form the loosely cross-linked points to mediate the cellulose chains’ self-assembly for achieving superior mechanical properties. The fabrication of the complex…

In this work, nanoparticles of a luminescent metal–organic framework were embedded in a photopolymerized methacrylated gelatin. Steady-state and time-resolved luminescence spectroscopy was used to explore the drying and the photopolymerization processes, as well as the effect the methacrylated gelatin had on the quantum yield and decay time of the nanoparticles. A drying time of 27.5 min was needed for a 20 µL droplet, and the proposed intensity ratio analysis resulted in a minimum irradiation time of 18.6 min, at a lamp intensity of 2.7 W/m2, for the photopolymerization process to end. The presence of the methacrylated gelatin decreased the quantum yield of the…

Critical bone defects with a sluggish rate of auto-osteoconduction and imperfect reconstruction are motivators for the development of an alternate innovative approach for the regeneration of bone. Tissue engineering for bone regeneration signifies an advanced way to overcome this problem by creating an additional bone tissue substitute. Among different fabrication techniques, the 3D printing technique is obviously the most efficient and advanced way to fabricate an osteoconductive scaffold with a controlled porous structure. In the current article, the polycarbonate and polyester diol based polyurethane–urea (P12) was synthesized and 3D porous nanohybrid scaffolds (P12/TP-nHA) were fabricated using the 3D printing technique…

Hip dysplasia is a developmental disorder that resulted in insufficient acetabular coverage. Current surgical treatments are technically demanding, complex, invasive, and often lead to associated complications. Therefore, the development of regenerative implants that fit to the bone and induce osteogenesis and chondrogenesis is in high demand. In this study, an implant was developed in which the osteogenic part was 3D printed using polycaprolactone (PCL), crosslinked with dopamine, and subjected to surface mineralization; while the chondrogenic part was prepared using silk fibroin (SF) and bone morphogenetic protein 2. Physical and chemical characterization of the implant was conducted using energy dispersive spectrometry…

Regeneration of the gradient structure of the tendon-to-bone interface is still a significant clinical challenge. This study reports a novel therapeutic method combining three-dimensional (3D) bioprinting and melt electrospinning writing techniques to regenerate a functional tendon-to-bone interface. We generated biomimetic multilayered scaffolds with 3D-bioprinted pre-differentiated autologous adipose-derived mesenchymal stem cells (ADMSC), which recapitulated compositional and cellular structures of the interface. The hydrogel-based bioinks offered high cell viability and proliferative capability for rabbit ADMSCs. The hydrogels with pre-differentiated (into tenogenic, chondrogenic, and osteogenic lineages) or undifferentiated rabbit ADMSCs were 3D-bioprinted into zonal-specific constructs to mimic the structure of the tendon-to-bone interface.…

Osteoarthritis is a highly prevalent rheumatic musculoskeletal disorder that commonly affects many joints. Repetitive joint overloading perpetuates the damage to the affected cartilage, which undermines the structural integrity of the osteochondral unit. Various tissue engineering strategies have been employed to design multiphasic osteochondral scaffolds that recapitulate layer-specific biomechanical properties, but the inability to fully satisfy mechanical demands within the joint has limited their success. Through computational modeling and extrusion-based bioprinting, we attempted to fabricate a biphasic osteochondral scaffold with improved shear properties and a mechanically strong interface. A 3D stationary solid mechanics model was developed to simulate the effect of…

4D printing is an advanced manufacturing technology combining additive manufacturing with smart materials. Based on light-active shape memory composites, smart medical structures with remote control capability, therapeutic function, and biocompatibility are hopefully fabricated by 4D printing. Here, a multifunctional composite with good mechanical properties, biocompatibility, and light-active shape memory performance is prepared by incorporating gold nanoparticles into a shape memory polyurethane matrix. The composites demonstrate a rapid and stable light-thermal effect, which can achieve localized and controlled breast tumor ablation, providing an approach to hyperthermia treatment for cancer cells. By directly bioprinting the composite melt, a series of 4D-printed structures…

Currently, the implants used for enophthalmic invagination have the disadvantages of precise filling difficulty, weak filling ability, large surgical wounds, and lack of CT development. Here, a CT-developable orbital stent was manufactured via 4D printing of a shape memory polyurethane composite for enophthalmos treatment. The composite was endowed with good CT development properties via incorporation of gold nanoparticles and nano-hydroxyapatite. Based on the bionic idea and CT reconstruction technique, a 4D printed orbital stent with a bionic honeycomb pore structure and an outer contour matching the orbital coloboma was designed to support the orbital tissue more accurately and stably. CT…

The cultured meat is the solution to reduce resources using in a traditional meat production. It helps produce meat without killing livestock and decrease residue products. The method could also integrate with scaffold’s material which does not derive from animal products. This study aims to investigate the effects of carboxymethyl cellulose (CMC) and apple powder on printability and cytotoxicity as additives in alginate/agarose-based hydrogel. 3D structures of them were printed to find a proper printing condition. From our experiments, the structure could maintain their shapes and uniform line sizes for carboxylmethyl cellulose, but not for apple powder at the 2%…

Cellulose nanocrystals (CNCs), a type of natural photonic crystal, have been used to develop various optical materials owing to their chiral nematic organization, renewability, sustainability, and abundance. However, scaling up the production of CNC-based photonic materials remains challenging because of their long self-assembly time, inevitable assembly defects, static optical properties, and brittle nature. To address these drawbacks, the current study introduces flexible photonic hydrogels with chromatic patterns that are 3D printed using CNC-based inks. These viscoelastic inks were composed of photopolymerizable monomers and CNCs that harbored high aspect ratios. The luminance and color difference of the patterns in the photonic…

Regenerative biomaterials play a crucial role in the success of maxillofacial reconstructive procedures. Yet today, limited options are available when choosing polymeric biomaterials to treat critical size bony defects. Further, there is a requirement for 3D printable regenerative biomaterials to fabricate customized structures confined to the defect site. We present here a 3D printable composite formulation consisting of polycaprolactone (PCL) and silk fibroin microfibers and have established a robust protocol for fabricating customized 3D structures of complex geometry with the composite. The 3D printed composite scaffolds demonstrated higher compressive modulus than 3D printed scaffolds of PCL alone. Furthermore, the compressive…

Three-dimensional (3D) printed hydrogel scaffolds enhanced with ceramics have shown potential applications for cartilage regeneration, but leaving biological and mechanical properties to be desired. This paper presents our study on the development of chitosan /alginate scaffolds with nano hydroxyapatite (nHA) by combining 3D printing and impregnating techniques, forming a hybrid, yet novel, structure of scaffolds for potential cartilage regeneration. First, we incorporated nHA into chitosan scaffold printing and studied the printability by examining the difference between the printed scaffolds and their designs. Then, we impregnated alginate with nHA into the printed chitosan scaffolds to forming a hybrid structure of scaffolds;…

Urinary tract disorders come at great discomfort to the patients suffering from them. To treat them, several potent drug substances are available but unfortunately, systemic drug therapy often comes along with undesired adverse effects. Previous work has therefore been conducted aiming at a local drug release in the urinary bladder. However, whether a therapeutically relevant drug concentration may be reached at the target site is not easy to determine when applying common compendial dissolution methods. Therefore, the aim of this study was to develop a biorelevant dissolution model able to take physiological conditions into consideration, i.e. urine flow rates, urination…

Discontinued treatment and non-adherence are oftentimes weaknesses of common first-line drug therapy against bladder conditions due to their negative side-effects. To overcome these limitations and increase patients’ quality of life, intravesical therapies are continuously being explored. 3D-printing offers the possibility of freely tailoring drug delivery systems to manufacture indwelling devices that may administer drugs locally over an extended time and avoiding frequently repeated administrations while minimizing systemic side-effects. In the present work, pressure-assisted micro syringe printing has been used to develop flexible drug-loaded inserts applicable via common urinary catheter that can remain up to several weeks inside the urinary bladder.…

In the field of orthopedics, an infected bone defect is a refractory disease accompanied by bone infection and defects as well as aggravated circulation. There are currently no personalized scaffolds that can treat bone infections using local stable and sustained-release antibiotics while providing mechanical support and bone induction to promote bone repair in the process of absorption in vivo. In our previous study, rifampicin/moxifloxacin-poly lactic-co-glycolic acid (PLGA) microspheres were prepared and tested for sustained release and antibacterial activity. The composite scaffold of poly-L-lactic acid (PLLA)/Pearl had a positive effect on mechanics supports and promoted osteogenesis. Therefore, in this study, the…

The efficiency of nerve guide conduits (NGCs) in repairing peripheral nerve injury is not high enough yet to be a substitute for autografts and is still insufficient for clinical use. To improve this efficiency, 3D electrospun scaffolds (3D/E) of poly(l-lactide-co-ε-caprolactone) (PLCL) and poly(l-lactide-co-glycolide) (PLGA) were designed and fabricated by the combination of 3D printing and electrospinning techniques, resulting in an ideal porous architecture for NGCs. Polypyrrole (PPy) was deposited on PLCL and PLGA scaffolds to enhance biocompatibility for nerve recovery. The designed pore architecture of these “PLCL-3D/E” and “PLGA-3D/E” scaffolds exhibited a combination of nano- and microscale structures. The mean…

Conventional manufacturing techniques allow the production of photoresponsive cellulose nanocrystals (CNC)-based composites that can reversibly modify their optical, mechanical, or chemical properties upon light irradiation. However, such materials are often limited to 2D films or simple shapes and do not benefit from spatial tailoring of mechanical properties resulting from CNC alignment. Herein, we propose the direct ink writing (DIW) of 3D complex structures that combine CNC reinforcement effects with photoinduced responses. After grafting azobenzene photochromes onto the CNC surfaces, up to 15 wt % of modified nanoparticles can be introduced into a polyurethane acrylate matrix. The influence of CNC on…

Personalised drug delivery systems with the ability to offer real-time imaging and control release are an advancement in diagnostic and therapeutic applications. This allows for a tailored drug dosage specific to the patient with a release profile that offers the optimum therapeutic effect. Coupling this application with medical imaging capabilities, real-time contrast can be viewed to display the interaction with the host. Current approaches towards such novelty produce a drug burst release profile and contrasting agents associated with side effects as a result of poor encapsulation of these components. In this study, a 3D-printed drug delivery matrix with real-time imaging…

Epigenetic approaches using the histone deacetylase 2 and 3 inhibitor-MI192 have been reported to accelerate stem cells to form mineralised tissues. Gelatine methacryloyl (GelMA) hydrogels provide a favourable microenvironment to facilitate cell delivery and support tissue formation. However, their application for bone repair is limited due to their low mechanical strength. This study aimed to investigate a GelMA hydrogel reinforced with a 3D printed scaffold to support MI192-induced human bone marrow stromal cells (hBMSCs) for bone formation. Cell culture: The GelMA (5 wt%) hydrogel supported the proliferation of MI192-pre-treated hBMSCs. MI192-pre-treated hBMSCs within the GelMA in osteogenic culture significantly increased…

A full PDMS micro-droplet chip for 3D cell culture was prepared by using SLA light-curing 3D printing technology. This technology can quickly customize various chips required for experiments, saving time and capital costs for experiments. Moreover, an injection molding method was used to prepare the full PDMS chip, and the convex mold was prepared by light-curing 3D printing technology. Compared with the traditional preparation process of micro-droplet chips, the use of 3D printing technology to prepare micro-droplet chips can save manufacturing and time costs. The different ratios of PDMS substrate and cover sheet and the material for making the convex…

Current in vitro models for osteosarcoma investigation and drug screening, including two-dimensional (2D) cell culture and tumour spheroids (i.e. cancer stem-like cells), lack extracellular matrix (ECM). Therefore, results from traditional models may not reflect real pathological processes in genuine osteosarcoma histological structures. Here, we report a three-dimensional (3D) bioprinted osteosarcoma model (3DBPO) that contains osteosarcoma cells and shrouding ECM analogue in a 3D frame. Photo-crosslinkable bioinks composed of gelatine methacrylamide and hyaluronic acid methacrylate mimicked tumour ECM. We performed multi-omics analysis, including transcriptomics and DNA methylomics, to determine differences between the 3DBPO model and traditional models. Compared with 2D models…

Protein delivery and release from synthetic scaffold materials are major challenges within the field of bone tissue engineering. In this study, 13-93B1.5 borosilicate bioactive glass (BSG) base paste was 3D printed to produce BSG-based scaffolds with high porosity (59.85 ± 6.04%) and large pore sizes (350–400 μm) for functionalization with a sodium alginate (SA)/calcitonin gene-related peptide (CGRP) hydrogel mixture. SA/CGRP hydrogel was uniformly filled into the interconnected pores of 3D printed BSG constructs to produce BSG-SA/CGRP scaffolds which were subject to bioactivity and biocompatibility analysis. BSG scaffolds filled with SA hydrogel underwent dissolution in simulated body fluid (SBF), resulting in…

High-dose methotrexate (HDMTX) is one of the chemotherapeutic agents used to treat a variety of cancers in both adults and children. However, the toxicity associated with HDMTX has resulted in the spread of infections and treatment interruption. Further, poor bioavailability due to efflux pump activities mediated by P-glycoprotein has also been linked to poor therapeutic effects of methotrexate following oral administrations. D-α-Tocopheryl poly-ethylene glycol 1000 succinate (TPGS) is known to improve the bioavailability of poorly soluble drugs by inhibiting P-gp efflux activities, thus enhancing cellular uptake. Therefore, to achieve improved bioavailability for MTX, this study aimed to design and develop…

3D printed ceramics have received much attention of late due to the ability to manufacture complex near net shapes with a range of structures across multiple length scales. The introduction of hierarchical features offers a wider array of properties, yet with this comes additional unknowns as to their limits including the mechanisms behind failures. The present work applies in-situ Synchrotron micro X-ray computed tomography (μXCT) with 4-point flexural testing to study and further understand the failure pattern of 3D printed hierarchical porous ultra-high temperature ceramics. Samples were imaged at incremental load steps to observe the propagation of defects until final…

Tissue engineering provides a promising strategy for auricular reconstruction. Although the first international clinical breakthrough of tissue-engineered auricular reconstruction has been realized based on polymer scaffolds, this approach has not been recognized as a clinically available treatment because of its unsatisfactory clinical efficacy. This is mainly since reconstruction constructs easily cause inflammation and deformation. In this study, we present a novel strategy for the development of biological auricle equivalents with precise shapes, low immunogenicity, and excellent mechanics using auricular chondrocytes and a bioactive bioink based on biomimetic microporous methacrylate-modified acellular cartilage matrix (ACMMA) with the assistance of gelatin methacrylate (GelMA),…

Fluoropolymers are amongst the most common polymers used for the fabrication of filtration membranes. Despite this, commercial production of these membranes remains dominated by simple casting and solvent phase separation. Herein, we show a rapid, simple approach to produce fluoropolymer membranes, with a porous patterned surface, via immersion precipitation printing (ipP). The patterns can act as a permeate spacer, which are traditionally added to a membrane separately to induce turbulent flow and subsequently decreasing membrane fouling. The direct phase inversion of the permeate spacer during membrane production induces a porous morphology. Further, intimate mechanical connection between the membrane surface and…

Introduction The use of scaffolds in tissue engineering is becoming increasingly important as solutions need to be found for the problem of preserving human tissue, such as bone or cartilage. In this work, scaffolds were printed from the biomaterial known as polycaprolactone (PCL) on a 3D Bioplotter. Both the external and internal geometry were varied to investigate their influence on mechanical stability and biocompatibility. Materials and Methods: An Envisiontec 3D Bioplotter was used to fabricate the scaffolds. First, square scaffolds were printed with variations in the strand width and strand spacing. Then, the filling structure was varied: either lines, waves,…

Yield-stress support bath-enabled three-dimensional (3D) printing has been widely used in recent years for diverse applications. However, current yield-stress fluids usually possess single microstructures and still face the challenges of on-demand adding and/or removing support bath materials during printing, constraining their application scope. This study aims to propose a concept of stimuli-responsive yield-stress fluids with an interactive dual microstructure as support bath materials. The microstructure from a yield-stress additive allows the fluids to present switchable states at different stresses, facilitating an embedded 3D printing process. The microstructure from stimuli-responsive polymers enables the fluids to have regulable rheological properties upon external…

Direct ink writing (DIW) is a promising extrusion-based 3D printing technology, which employs an ink-deposition nozzle to fabricate 3D scaffold structures with customizable ink formulations for tissue engineering applications. However, determining the optimal DIW process parameters such as temperature, pressure, and speed for the specific ink is essential to achieve high reproducibility of the designed geometry and subsequent mechano-biological performance for different applications, particularly for porous scaffolds of finite sizes (total volume > 1000 mm3) and controlled pore size and porosity. The goal of this study was to evaluate the feasibility of fabricating Polycaprolactone (PCL) and bio-active glass (BG) composite-based…

Background To support bone regeneration, 3D-printed templates function as temporary guides. The preferred materials are synthetic polymers, due to their ease of processing and biological inertness. Poly(lactide-co-trimethylene carbonate) (PLATMC) has good biological compatibility and currently used in soft tissue regeneration. The aim of this study was to evaluate the osteoconductivity of 3D-printed PLATMC templates for bone tissue engineering, in comparison with the widely used 3D-printed polycaprolactone (PCL) templates. Methods The printability and physical properties of 3D-printed templates were assessed, including wettability, tensile properties and the degradation profile. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were used to evaluate osteoconductivity and…

Three-dimensional printing (3D printing) is a promising technique for producing scaffolds for bone tissue engineering applications. Porous scaffolds can be printed directly, and the design, shape and porosity can be controlled. 3D synthetic biodegradable polymeric scaffolds intended for in situ bone regeneration must meet stringent criteria, primarily appropriate mechanical properties, good 3D design, adequate biocompatibility and the ability to enhance bone formation. In this study, healing of critical-sized (5 ​mm) femur defects of rats was enhanced by implanting two different designs of 3D printed poly(l-lactide-co-ε-caprolactone) (poly(LA-co-CL)) scaffolds seeded with rat bone marrow mesenchymal stem cells (rBMSC), which had been pre-differentiated…

The generation of monoclonal antibodies using an in vitro immunization approach is a promising alternative to conventional hybridoma technology. As recently published, the in vitro approach enables an antigen-specific activation of B lymphocytes within 10–12 d followed by immortalization and subsequent selection of hybridomas. This in vitro process can be further improved by using a three-dimensional surrounding to stabilize the complex microenvironment required for a successful immune reaction. In this study, the suitability of Geltrex as a material for the generation of monoclonal antigen-specific antibodies by in vitro immunization was analyzed. We could show that dendritic cells, B cells, and…

In this project, different calcification methods for collagen and collagen coatings were compared in terms of their applicability for 3D printing and production of collagen-coated scaffolds. For this purpose, scaffolds were printed from polycaprolactone PCL using the EnvisionTec 3D Bioplotter and then coated with collagen. Four different coating methods were then applied: hydroxyapatite (HA) powder directly in the collagen coating, incubation in 10× SBF, coating with alkaline phosphatase (ALP), and coating with poly-L-aspartic acid. The results were compared by ESEM, µCT, TEM, and EDX. HA directly in the collagen solution resulted in a pH change and thus an increase in…

The development of a well-designed tissue-engineered blood vessel (TEBV) still remains a challenge. In recent years, approaches in which the host response to implanted biomaterials is used to generate vascular constructs within the patient’s body have gained increasing interest. The delivery of growth factors to these in situ-engineered vascular grafts might enhance myofibroblast recruitment and the secretion of essential extracellular matrix proteins, thereby optimizing their functional properties. Layer-by-layer (LbL) coating has emerged as an innovative technology for the controlled delivery of growth factors in tissue engineering applications. In this study, we combined the use of surface-etched polymeric rods with LbL…

Carbon-based materials are promising candidates for enhancing thermal properties of phase change materials (PCMs) without lowering its energy storage capacity. Nowadays, researchers are trying to find a proper porous structure as PCMs support for thermal energy storage applications. In this context, the main novelty of this paper consists in using a ZnO-CNT-based nanocomposite powder, prepared by an own hydrothermal method at high pressure, to obtain porous 3D printed support structures with embedding capacity of PCMs. The morphology of 3D structures, before and after impregnation with three PCMs inorganic salts (NaNO3, KNO3 and NaNO3:KNO3 mixture (1:1 vol% saturated solution) was investigated…

This study aimed to fabricate biodegradable substrate with colorimetric humidity indicator for detective moisture in food packaging. The poor properties of poly(lactic acid) (PLA) were enhanced by melt blending PLA with non-toxic poly(ethylene oxide) PEO at 180 °C. Specifically, three-dimensional (3D) substrates of PLA/PEO blends were fabricated by solvent-cast 3D printing. Furthermore, cobalt chloride (CoCl2) solution was printed onto the substrate with an inkjet printer to serve as a colorimetric humidity sensing indicator. It found that the flexibility and thermal stability of the PLA were improved and the hydrophilicity was increased with an increase in PEO content. Color changes and…

In the literature, many studies have described the 3D printing of ceramic-based scaffolds (e.g., printing with calcium phosphate cement) in the form of linear structures with layer rotations of 90°, although no right angles can be found in the human body. Therefore, this work focuses on the adaptation of biological shapes, including a layer rotation of only 1°. Sample shapes were printed with calcium phosphate cement using a 3D Bioplotter from EnvisionTec. Both straight and wavy spokes were printed in a round structure with 12 layers. Depending on the strand diameter (200 and 250 µm needle inner diameter) and strand…

Cardiac tissue engineering has emerged as a promising strategy to treat infarcted cardiac tissues by replacing the injured region with an ex vivo fabricated functional cardiac patch. Nevertheless, integration of the transplanted patch with the host tissue is still a burden, limiting its clinical application. Here, a bi-functional, 3D bio-printed cardiac patch (CP) design is proposed, composed of a cell-laden compartment at its core and an extracellular vesicle (EV)-laden compartment at its shell for better integration of the CP with the host tissue. Alginate-based bioink solutions were developed for each compartment and characterized rheologically, examined for printability and their effect…

The 3D printing has become important in drug development for patient-centric therapy by combining multiple drugs with different release characteristics in a single polypill. This study explores the critical formulation and geometric variables for tailoring the release of Atorvastatin and Metoprolol as model drugs in a polypill when manufactured via pressure-assisted-microextrusion 3D printing technology. The effects of these variables on the extrudability of printing materials, drug release and other quality characteristics of polypills were studied employing a definitive screening design. The extrudability of printing materials was evaluated in terms of flow pressure, non-recoverable strain, compression rate, and elastic/plastic flow. The…

In the field of regenerative medicine and tissue engineering, the use of such materials has been included for a short time, serving not only as a replacement for damaged or missing tissue, but also as a support for the surrounding tissues and cells. Such materials should not only be passively tolerated by the cell, but should also actively promote the growth, differentiation and other processes involved in tissue regeneration. The latest approach is the use and development of bioresorbable and biodegradable polymeric materials. Such materials, with their biocompatibility, degradability and suitable mechanical properties, support the overgrowth of new tissue. The…

Massive oral and maxillofacial bone defect regeneration remains a major clinical challenge due to the absence of functionalized bone grafts with ideal mechanical and proregeneration properties. In the present study, Laponite (LAP), a synthetic nanosilicate, is incorporated into polycaprolactone (PCL) to develop a biomaterial for bone regeneration. It is explored whether LAP-embedded PCL would accelerate bone regeneration by orchestrating osteoblasts to directly and indirectly induce bone regeneration processes. The results confirmed the presence of LAP in PCL, and LAP is distributed in the exfoliated structure without aggregates. Incorporation of LAP in PCL slightly improved the compressive properties. LAP-embedded PCL is…

Advances in 3D bioprinting allows not only controlled deposition of cells or cell-laden hydrogels but also flexibility in creating constructs that match the anatomical features of the patient. This is especially the case for reconstructing the pinna (ear), which is a large feature of the face and made from elastic cartilage that primarily relies on diffusion for nutrient transfer. The selection of cell lines for reconstructing this cartilage becomes a crucial step in clinical translation. Chondrocytes and mesenchymal stem cells are both studied extensively in the area of cartilage regeneration as they are capable of producing cartilage in vitro. However,…

Micropores are essential for tissue engineering to ensure adequate mass transportation for embedded cells. Despite the considerable progress made by advanced 3D bioprinting technologies, it remains challenging to engineer micropores of 100 µm or smaller in cell-laden constructs. Here, a microgel-templated porogel (MTP) bioink platform is reported to introduce controlled microporosity in 3D bioprinted hydrogels in the presence of living cells. Templated gelatin microgels are fabricated with varied sizes (≈10, ≈45, and ≈100 µm) and mixed with photo-crosslinkable formulations to make composite MTP bioinks. The addition of microgels significantly enhances the shear-thinning and self-healing viscoelastic properties and thus the printability of bioinks…

The three-dimensional (3D)-printing processes reach increasing recognition as important fabrication techniques to meet the growing demands in tissue engineering. However, it is imperative to fabricate 3D tissue units, which contain cells that have the property to be regeneratively active. In most bio-inks, a metabolic energy-providing component is missing. Here a formulation of a bio-ink is described, which is enriched with polyphosphate (polyP), a metabolic energy providing physiological polymer. The bio-ink composed of a scaffold (N,O-carboxymethyl chitosan), a hydrogel (alginate) and a cell adhesion matrix (gelatin) as well as polyP substantially increases the viability and the migration propensity of mesenchymal stem…

Polymeric systems displaying spontaneous formation of surface wrinkling patterns are useful for a wide range of applications, such as diffraction gratings, flexible electronics, smart adhesives, optical devices, and cell culture platforms. Conventional fabrication techniques for wrinkling patterns involves multitude of processing steps and impose significant limitations on fabrication of hierarchical patterns, creating wrinkles on 3D and nonplanar structures, the scalability of the manufacturing process, and the integration of wrinkle fabrication process into a continuous manufacturing process. In this work, 4D printing of surface morphing hydrogels enabling direct fabrication of wrinkling patterns on curved and/or 3D structures with user-defined and spatially…

Pb0.99(Zr0.95Ti0.05)0.98Nb0.02O3 ferroelectric ceramics with porous structure of periodic distribution were fabricated successfully via Direct Ink Writing, a type of 3D printing technique. The effect of periodically distributed porous microstructure on the dielectric, ferroelectric, as well as hydrostatic-pressure-induced depolarization properties of PZT95/5 ferroelectric ceramics, was investigated. The printed porous ceramics exhibit relatively good viscoelasticity to retain the periodic structure during 3D printing and drying. In contrast with dense PZT95/5 ferroelectric ceramics prepared by conventional solid-state sintering, low bulk density of the periodically distributed porous PZT95/5 ceramics leads to a decreased remanent polarization of 22.9 µC/cm2 under 2 kV/mm. As the hydrostatic pressure…

The 3D printability of poly(l-lysine-ran–l-alanine) and four-arm poly(ethylene glycol) (P(KA)/4-PEG) hydrogels as 3D biomaterial inks was investigated using two approaches to develop P(KA)/4-PEG into 3D biomaterial inks. Only the “composite microgel” inks were 3D printable. In this approach, P(KA)/4-PEG hydrogels were processed into microparticles and incorporated into a polymer solution to produce a composite microgel paste. Polymer solutions composed of either 4-arm PEG-acrylate (4-PEG-Ac), chitosan (CS), or poly(vinyl alcohol) (PVA) were used as the matrix material for the composite paste. The three respective composite microgel inks displayed good 3D printability in terms of extrudability, layer-stacking ability, solidification mechanism, and 3D…

Objective Alveolar bone defects can be highly variable in their morphology and, as the defect size increases, they become more challenging to treat with currently available therapeutics and biomaterials. This investigation sought to devise a protocol for fabricating customized clinical scale and patient-specific, bioceramic scaffolds for reconstruction of large alveolar bone defects. Methods Two types of calcium phosphate (CaP)-based bioceramic scaffolds (alginate/β-TCP and hydroxyapatite/α-TCP, hereafter referred to as hybrid CaP and Osteoink™, respectively) were designed, 3D printed, and their biocompatibility with alveolar bone marrow stem cells and mechanical properties were determined. Following scaffold optimization, a workflow was developed to use…

The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone, most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells. Human umbilical vein endothelial cell-derived decellularized extracellular matrix (HdECM), which contains a collection of angiocrine biomolecules, has recently been demonstrated to mediate endothelial cells(ECs) – osteoprogenitors(OPs) crosstalk. We employed the HdECM to create a PCL (polycaprolactone)/fibrin/HdECM (PFE) hybrid scaffold. We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk, resulting in vascularized bone regeneration. Following implantation in a…

Bone defects remain a major threat to human health and bone tissue regeneration has become a prominent clinical demand worldwide. The combination of microRNA (miRNA) therapy with 3D printed scaffolds has always posed a challenge. It can mimic physiological bone healing processes, in which a biodegradable scaffold is gradually replaced by neo-tissue, and the sustained release of miRNA plays a vital role in creating an optimal osteogenic microenvironment, thus achieving promising bone repair outcomes. However, the balance between two key factors – scaffold degradation behavior and miRNA release profile – on osteogenesis and bone formation is still poorly understood. Herein,…