3D Bioplotter Research Papers

Injuries affecting load bearing tendon tissues are a significant clinical burden and efficient treatments are still unmet. Tackling tendon regeneration, tissue engineering strategies aim to develop functional substitutes that recreate native tendon milieu. Tendon mimetic scaffolds capable of remote magnetic responsiveness and functionalized magnetic nanoparticles (MNPs) targeting cellular mechanosensitive receptors are potential instructive tools to mediate mechanotransduction in guiding tenogenic responses. In this work, we combine magnetically responsive scaffolds and targeted Activin A type II receptor in human adipose stem cells (hASCs), under alternating magnetic field (AMF), to synergistically facilitate external control over signal transduction. The combination of remote triggering…

The meniscus has critical functions in the knee joint kinematics and homeostasis. Injuries of the meniscus are frequent, and the lack of a functional meniscus between the femur and tibial plateau can cause articular cartilage degeneration leading to osteoarthritis development and progression. Regeneration of meniscus tissue has outstanding challenges to be addressed. In the current study, novel Entrapped in cage (EiC) scaffolds of 3D-printed polycaprolactone (PCL) and porous silk fibroin were proposed for meniscus tissue engineering. As confirmed by micro-structural analysis the entrapment of silk fibroin was successful, and all scaffolds had excellent interconnectivity (≥99%). The EiC scaffolds had more…

The menisci have crucial roles in the knee, chondroprotection being the primary. Meniscus repair or substitution is favored in the clinical management of the meniscus lesions with given indications. The outstanding challenges with the meniscal scaffolds include the required biomechanical behavior and features. Suturability is one of the prerequisites for both implantation and implant survival. Therefore, we proposed herein a novel highly interconnected suturable porous scaffolds from regenerated silk fibroin that is reinforced with 3D-printed polycaprolactone (PCL) mesh in the middle, on the transverse plane to enhance the suture-holding capacity. Results showed that the reinforcement of the silk fibroin scaffolds…

Lower back pain (LBP), which is strongly associated with intervertebral disc (IVD) degeneration, is one of the most frequently reported age- and work-related disorder in actual society, leading to a huge socio-economic impact worldwide. The current treatments have poor clinical outcomes and do not consider each patient needs. Thus, there is a growing interest in the potential of personalized cell-based tissue engineering (TE) approaches aimed to regenerate the damaged IVD and efficiently restore full disc function. In this work, a bioink composed by silk fibroin (SF) hydrogel combined with elastin was used to bioprint patient-specific substitutes mimicking IVD ultrastructure, in…

The pursuit for the “perfect” biomimetic and personalized implant for musculoskeletal tissue regeneration remains a big challenge. 3D printing technology that makes use of a novel and promising biomaterials can be part of the solution. In this study, a fast setting enzymatic-crosslinked silk fibroin (SF) bioink for 3D bioprinting is developed. Their properties are fine-tuned and different structures with good resolution, reproducibility, and reliability can be fabricated. Many potential applications exist for the SF bioinks including 3D bioprinted scaffolds and patient-specific implants exhibiting unique characteristics such as good mechanical properties, memory-shape feature, suitable degradation, and tunable pore architecture and morphology.

Collagen is the most abundant protein found in mammals and it exhibits a low immunogenicity, high biocompatibility and biodegradability when compared with others natural polymers. For this reason, it has been explored for the development of biologically instructive biomaterials with applications for tissue substitution and regeneration. Marine origin collagen has been pursued as an alternative to the more common bovine and porcine origins. This study focused on squid (Teuthoidea: Cephalopoda), particularly the Antarctic squid Kondakovia longimana and the Sub-Antarctic squid Illex argentinus as potential collagen sources. In this study, collagen has been isolated from the skins of the squids using…

Aim: To develop a methodology for producing patient-specific scaffolds that mimic the annulus fibrosus (AF) of the human intervertebral disc by means of combining MRI and 3D bioprinting. Methods: In order to obtain the AF 3D model from patient’s volumetric MRI dataset, the RheumaSCORE segmentation software was used. Polycaprolactone scaffolds with three different internal architectures were fabricated by 3D bioprinting, and characterized by microcomputed tomography. Results: The demonstrated methodology of a geometry reconstruction pipeline enabled us to successfully obtain an accurate AF model and 3D print patient-specific scaffolds with different internal architectures. Conclusion: The results guide us toward patient-specific intervertebral…

The current strategies for the transplantation of meniscus should be strengthened to tackle the faced limitations of current methods in the clinics. One of the limitations is that current implants are not patient-specific. There is, therefore, a pressing need in the clinics to develop patient-specific implants. The aim of this study was to demonstrate a semi-automatic way of segmenting meniscus tissues from patients’ volumetric knee magnetic resonance imaging (MRI) datasets in order to obtain patient-specific 3D models for 3D printing of patient-specific constructs. High-quality MRI volumetric images were acquired from five healthy male human subjects. The advanced segmentation software, RheumaSCORE,…

The present study aimed to investigate the effect of structure (design and porosity) on the matrix stiffness and osteogenic activity of stem cells cultured on poly(ester-urethane) (PEU) scaffolds. Different three-dimensional (3D) forms of scaffold were prepared from lysine-based PEU using traditional salt-leaching and advanced bioplotting techniques. The resulting scaffolds were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), mercury porosimetry and mechanical testing. The scaffolds had various pore sizes with different designs, and all were thermally stable up to 300 °C. In vitro tests, carried out using rat bone marrow stem cells (BMSCs) for bone tissue…

Spine stabilization upon spinal cord injury (SCI) is a standard procedure in clinical practice, but rarely employed in experimental models. Moreover, the application of biodegradable biomaterials for this would come as an advantage as it would eliminate the presence of a nondegradable prosthesis within the vertebral bone. Therefore, in the present work, we propose the use of a new biodegradable device specifically developed for spine stabilization in a rat model of SCI. A 3D scaffold based on a blend of starch with polycaprolactone was implanted, replacing delaminated vertebra, in male Wistar rats with a T8-T9 spinal hemisection. The impact of…

A new application of layer-by-layer assembly is presented, able to create nano/micro fibrils or nanocoatings inside 3D scaffolds using non-fibrillar polyelectrolytes for tissue-engineering applications. This approach shows promise for developing advanced scaffolds with controlled nano/micro environments, and nature and architectures similar to the natural extracellular matrix, leading to improved biological performance.

The hypothesis of this study was that the extent of bone regeneration could be enhanced by using scaffolds with appropriate geometry, and that such an effect could be further increased by mimicking the natural timing of appearance of bone morphogenetic proteins BMP-2 and BMP-7 after fracture. Bioplotted poly(ε-caprolactone) (PCL) disks with four different fibre organizations were used to study the effect of 3D scaffold architecture on the healing of bone defects in a rat pelvis model. Moreover, one PCL construct was further modified by introducing a nanoparticulate sequential BMP-2/BMP-7 delivery system into this scaffold. Scaffolds and functionalized construct along with…

Spinal cord injuries (SCI) present a major challenge to therapeutic development due to its complexity. Combinatorial approaches using biodegradable polymers that can simultaneously provide a tissue scaffold, a cell vehicle, and a reservoir for sustained drug delivery have shown very promising results. In our previous studies we have developed a novel hybrid system consisting of starch/poly-e-caprolactone (SPCL) semi-rigid tubular porous structure, based on a rapid prototyping technology, filled by a gellan gum hydrogel concentric core for the regeneration within spinal-cord injury sites. In the present work we intend to promote enhanced osteointegration on these systems by pre-mineralizing specifically the external…

Spinal cord injury (SCI) represents a major world health problem. Therefore it is urgent to develop novel strategies that can specifically target it. We have previously shown that the implantation of starch-based scaffolds (SPCL) aimed for spine stabilization on SCI animals leads to motor skills improvements. Therefore, we hypothesize that the combination of these scaffolds with relevant cell populations for SCI repair will, most likely, lead to further improvements. Therefore, in this work, the ability of SPCL scaffolds to support the 3D culture of olfactory ensheathing cells (OECs) and Schwann cells (SCs) was studied and characterized. The results demonstrate for…

Scaffolds produced by rapid prototyping (RP) techniques have proved their value for tissue engineering applications, due to their ability to produce predetermined forms and structures featuring fully interconnected pore architectures. Nevertheless, low cell seeding efficiency and non-uniform distribution of cells remain major limitations when using such types of scaffold. This can be mainly attributed to the inadequate pore architecture of scaffolds produced by RP and the limited efficiency of cell seeding techniques normally adopted. In this study we aimed at producing scaffolds with pore size gradients to enhance cell seeding efficiency and control the spatial organization of cells within the…

Spinal cord injury (SCI) represents a significant health and social problem, and therefore it is vital to develop novel strategies that can specifically target it. In this context, the objective of the present work was to develop a new range of three-dimensional (3D) tubular structures aimed at inducing the regeneration within SCI sites. Up to six different 3D tubular structures were initially developed by rapid prototyping: 3D bioplotting–based on a biodegradable blend of starch. These structures were then further complemented by injecting Gellan Gum, a polysaccharide-based hydrogel, in the central area of structures. The mechanical properties of these structures were…

The aim of this study was to develop 3-D tissue engineered constructs that mimic the in vivo conditions through a self-contained growth factor delivery system. A set of nanoparticles providing the release of BMP-2 initially followed by the release of BMP-7 were incorporated in poly(ε-caprolactone) scaffolds with different 3-D architectures produced by 3-D plotting and wet spinning. The release patterns were: each growth factor alone, simultaneous, and sequential. The orientation of the fibers did not have a significant effect on the kinetics of release of the model protein BSA; but affected proliferation of bone marrow mesenchymal stem cells. Cell proliferation…

Apatite layers were grown on the surface of newly developed starch/polycaprolactone (SPCL)-based scaffolds by a 3D plotting technology. To produce the biomimetic coatings, a sodium silicate gel was used as nucleating agent, followed by immersion in a simulated body fluid (SBF) solution. After growing a stable apatite layer for 7 days, the scaffolds were placed in SBF under static, agitated (80 strokes min−1) and circulating flow perfusion (Q = 4 ml min−1; tR = 15 s) for up to 14 days. The materials were characterized by scanning electron microscopy/energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy and thin-film X-ray diffraction….

Fibrous structures mimicking the morphology of the natural extracellular matrix are considered promising scaffolds for tissue engineering. This work aims to develop a novel hierarchical starch-based scaffold. Such scaffolds were obtained by a combination of starch-polycaprolactone micro- and polycaprolactone nano-motifs, respectively produced by rapid prototyping (RP) and electrospinning techniques. Scanning electron microscopy (SEM) and micro-computed tomography analysis showed the successful fabrication of a multilayer scaffold composed of parallel aligned microfibres in a grid-like arrangement, intercalated by a mesh-like structure with randomly distributed nanofibres (NFM). Human osteoblast-like cells were dynamically seeded on the scaffolds, using spinner flasks, and cultured for 7…

The ability to control the architecture and strength of a bone tissue engineering scaffold is critical to achieve a harmony between the scaffold and the host tissue. Rapid prototyping (RP) technique is applied to tissue engineering to satisfy this need and to create a scaffold directly from the scanned and digitized image of the defect site. Design and construction of complex structures with different shapes and sizes, at micro and macro scale, with fully interconnected pore structure and appropriate mechanical properties are possible by using RP techniques. In this study, RP was used for the production of poly(ε-caprolactone) (PCL) scaffolds….