3D Bioprinted Hydroxyapatite or Graphene Oxide Containing Nanocellulose-Based Scaffolds for Bone Regeneration.

Bone tissue is usually damaged after big traumas, tumors, and increasing aging-related diseases such as osteoporosis and osteoarthritis. Current treatments are based on implanting grafts, which are shown to have several inconveniences. In this regard, tissue engineering through the 3D bioprinting technique has arisen to manufacture structures that would be a feasible therapeutic option for bone regenerative medicine. In this study, nanocellulose-alginate (NC-Alg)-based bioink is improved by adding two different inorganic components such as hydroxyapatite (HAP) and graphene oxide (GO). First, ink rheological properties and biocompatibility are evaluated as well as the influence of the sterilization process on them. Then, scaffolds are characterized. Finally, biological studies of embedded murine D1 mesenchymal stem cells engineered to secrete erythropoietin are performed. Results show that the addition of both HAP and GO prevents NC-Alg ink from viscosity lost in the sterilization process. However, GO is reduced due to short cycle autoclave sterilization, making it incompatible with this ink. In addition, HAP and GO have different influences on scaffold architecture and surface as well as in swelling capacity. Scaffolds mechanics, as well as cell viability and functionality, are promoted by both elements addition. Additionally, GO demonstrates an enhanced bone differentiation capacity.

Progress in 3D Bioprinting Technology for Osteochondral Regeneration.

Osteochondral injuries can lead to osteoarthritis (OA). OA is characterized by the progressive degradation of the cartilage tissue together with bone tissue turnover. Consequently, joint pain, inflammation, and stiffness are common, with joint immobility and dysfunction being the most severe symptoms. The increase in the age of the population, along with the increase in risk factors such as obesity, has led OA to the forefront of disabling diseases. In addition, it not only has an increasing prevalence, but is also an economic burden for health systems. Current treatments are focused on relieving pain and inflammation, but they become ineffective as the disease progresses. Therefore, new therapeutic approaches, such as tissue engineering and 3D bioprinting, have emerged. In this review, the advantages of using 3D bioprinting techniques for osteochondral regeneration are described. Furthermore, the biomaterials, cell types, and active molecules that are commonly used for these purposes are indicated. Finally, the most recent promising results for the regeneration of cartilage, bone, and/or the osteochondral unit through 3D bioprinting technologies are considered, as this could be a feasible therapeutic approach to the treatment of OA.

Chondroitin and Dermatan Sulfate Bioinks for 3D Bioprinting and Cartilage Regeneration.

Cartilage is a connective tissue which a limited capacity for healing and repairing. In this context, osteoarthritis (OA) disease may be developed with high prevalence in which the use of scaffolds may be a promising treatment. In addition, three-dimensional (3D) bioprinting has become an emerging additive manufacturing technology because of its rapid prototyping capacity and the possibility of creating complex structures. This study is focused on the development of nanocellulose-alginate (NC-Alg) based bioinks for 3D bioprinting for cartilage regeneration to which it is added chondroitin sulfate (CS) and dermatan sulfate (DS). First, rheological properties are evaluated. Then, sterilization effect, biocompatibility, and printability on developed NC-Alg-CS and NC-Alg-DS inks are evaluated. Subsequently, printed scaffolds are characterized. Finally, NC-Alg-CS and NC-Alg-DS inks are loaded with murine D1-MSCs-EPO and cell viability and functionality, as well as the chondrogenic differentiation ability are assessed. Results show that the addition of both CS and DS to the NC-Alg ink improves its characteristics in terms of rheology and cell viability and functionality. Moreover, differentiation to cartilage is promoted on NC-Alg-CS and NC-Alg-DS scaffolds. Therefore, the utilization of MSCs containing NC-Alg-CS and NC-Alg-DS scaffolds may become a feasible tissue engineering approach for cartilage regeneration.

Clay Minerals as Bioink Ingredients for 3D Printing and 3D Bioprinting: Application in Tissue Engineering and Regenerative Medicine.

The adaptation and progress of 3D printing technology toward 3D bioprinting (specifically adapted to biomedical purposes) has opened the door to a world of new opportunities and possibilities in tissue engineering and regenerative medicine. In this regard, 3D bioprinting allows for the production of tailor-made constructs and organs as well as the production of custom implants and medical devices. As it is a growing field of study, currently, the attention is heeded on the optimization and improvement of the mechanical and biological properties of the so-called bioinks/biomaterial inks. One of the strategies proposed is the use of inorganic ingredients (clays, hydroxyapatite, graphene, carbon nanotubes and other silicate nanoparticles). Clays have proven to be useful as rheological and mechanical reinforcement in a wide range of fields, from the building industry to pharmacy. Moreover, they are naturally occurring materials with recognized biocompatibility and bioactivity, revealing them as optimal candidates for this cutting-edge technology. This review deals with the use of clays (both natural and synthetic) for tissue engineering and regenerative medicine through 3D printing and bioprinting. Despite the limited number of studies, it is possible to conclude that clays play a fundamental role in the formulation and optimization of bioinks and biomaterial inks since they are able to improve their rheology and mechanical properties, thus improving printability and construct resistance. Additionally, they have also proven to be exceptionally functional ingredients (enhancing cellular proliferation, adhesion, differentiation and alignment), controlling biodegradation and carrying/releasing actives with tissue regeneration therapeutic activities.

Tendon tissue engineering: Cells, growth factors, scaffolds and production techniques.

Tendon injuries are a global health problem that affects millions of people annually. The properties of tendons make their natural rehabilitation a very complex and long-lasting process. Thanks to the development of the fields of biomaterials, bioengineering and cell biology, a new discipline has emerged, tissue engineering. Within this discipline, diverse approaches have been proposed. The obtained results turn out to be promising, as increasingly more complex and natural tendon-like structures are obtained. In this review, the nature of the tendon and the conventional treatments that have been applied so far are underlined. Then, a comparison between the different tendon tissue engineering approaches that have been proposed to date is made, focusing on each of the elements necessary to obtain the structures that allow adequate regeneration of the tendon: growth factors, cells, scaffolds and techniques for scaffold development. The analysis of all these aspects allows understanding, in a global way, the effect that each element used in the regeneration of the tendon has and, thus, clarify the possible future approaches by making new combinations of materials, designs, cells and bioactive molecules to achieve a personalized regeneration of a functional tendon.

Current Insights Into 3D Bioprinting: An Advanced Approach for Eye Tissue Regeneration.

Three-dimensional (3D) printing is a game changer technology that holds great promise for a wide variety of biomedical applications, including ophthalmology. Through this emerging technique, specific eye tissues can be custom-fabricated in a flexible and automated way, incorporating different cell types and biomaterials in precise anatomical 3D geometries. However, and despite the great progress and possibilities generated in recent years, there are still challenges to overcome that jeopardize its clinical application in regular practice. The main goal of this review is to provide an in-depth understanding of the current status and implementation of 3D bioprinting technology in the ophthalmology field in order to manufacture relevant tissues such as cornea, retina and conjunctiva. Special attention is paid to the description of the most commonly employed bioprinting methods, and the most relevant eye tissue engineering studies performed by 3D bioprinting technology at preclinical level. In addition, other relevant issues related to use of 3D bioprinting for ocular drug delivery, as well as both ethical and regulatory aspects, are analyzed. Through this review, we aim to raise awareness among the research community and report recent advances and future directions in order to apply this advanced therapy in the eye tissue regeneration field.