Bioprinting of gelatin-based materials for orthopedic application.

Bio-printed hydrogels have evolved as one of the best regenerative medicine and tissue engineering platforms due to their outstanding cell-friendly microenvironment. A correct hydrogel ink formulation is critical for creating desired scaffolds that have better fidelity after printing. Gelatin and its derivatives have sparked intense interest in various biomedical sectors because of their biocompatibility, biodegradability, ease of functionalization, and rapid gelling tendency. As a result, this report emphasizes the relevance of gelatin-based hydrogel in fabricating bio-printed scaffolds for orthopedic applications. Starting with what hydrogels and bio-printing are all about. We further summarized the different gelatin-based bio-printing techniques explored for orthopedic applications, including a few recent studies. We also discussed the suitability of gelatin as a biopolymer for both 3D and 4D printing materials. As extrusion is one of the most widely used techniques for bio-printing gelatin-based, we summarize the rheological features of gelatin-based bio-ink. Lastly, we also elaborate on the recent bio-printed gelatin-based studies for orthopedics applications, the potential clinical translation issues, and research possibilities.

Study of the surgical needle and biological soft tissue interaction phenomenon during insertion process for medical application: A Survey.

The insertion of the surgical needle in soft tissue has involved significant interest in the current time because of its purpose in minimally invasive surgery (MIS) and percutaneous events like biopsies, PCNL, and brachytherapy. This study represents a review of the existing condition of investigation on insertion of a surgical needle in biological living soft tissue material. As observes the issue from numerous phases, like, analysis of the cutting forces modeling (insertion), tissue material deformation, analysis of the needle deflection for the period of the needle insertion, and the robot-controlled insertion procedures. All analysis confirms that the total needle insertion force is the total of dissimilar forces spread sideways the shaft of the insertion needle for example cutting force, stiffness force, and frictional force. Various investigations have analyzed all these kinds of forces during the needle insertion process. The force data in several measures are applied for recognizing the biological tissue materials as the needle is penetrated or for path planning. The deflection of the needle during insertion and tissue material deformation is the main trouble for defined needle placing and efforts have been prepared to model them. Applying existing models numerous insertion methods are established that are discussed in this review.

A Micro-Scale Non-Linear Finite Element Model to Optimize the Mechanical Behavior of Bioprinted Constructs.

Extrusion-based bioprinting is an enabling biofabrication technique that is used to create heterogeneous tissue constructs according to patient-specific geometries and compositions. The optimization of bioinks as per requirements for specific tissue applications is an essential exercise in ensuring clinical translation of the bioprinting technologies. Most notably, optimum hydrogel polymer concentrations are required to ensure adequate mechanical properties of bioprinted constructs without causing significant shear stresses on cells. However, experimental iterations are often tedious for optimizing the bioink properties. In this work, a nonlinear finite element modeling approach has been undertaken to determine the effect of different bioink parameters such as composition, concentration on the range of stresses being experienced by the cells in the bioprinted construct. The stress distribution of the cells at different parts of the constructs has also been modeled. It is found that both bioink chemical compositions and concentrations can substantially alter the stress effects experienced by the cells. Concentrated regions of softer cells near pore regions were found to increase stress concentrations by almost three times compared with stress generated in cells away from the pores. The study provides a method for rapid optimization of bioinks, design of bioprinted constructs, as well as toolpath plans for fabricating constructs with homogenous properties.

Bioprinting of radiopaque constructs for tissue engineering and understanding degradation behavior by use of Micro-CT.

Bioprinting has emerged as a potential technique to fabricate tissue engineering constructs and in vitro models directly using living cells as a raw material for fabrication, conforming to the heterogeneity and architectural complexity of the tissues. In several of tissue engineering and in vitro disease modelling or surgical planning applications, it is desirable to have radiopaque constructs for monitoring and evaluation. In the present work, enhanced radiopaque constructs are generated by substituting Calcium ions with Barium ions for crosslinking of alginate hydrogels. The constructs are characterized for their structural integrity and followed by cell culture studies to evaluate their biocompatibility. This was followed by the radiopacity evaluation. The radiological images obtained by micro-CT technique was further applied to investigate the degradation behavior of the scaffolds. In conclusion, it is observed that barium crosslinking can provide a convenient means to obtain radiopaque constructs with potential for multi-faceted applications.

Force modeling to develop a novel method for fabrication of hollow channels inside a gel structure.

Fabrication of hollow channels with user-defined dimensions and patterns inside viscoelastic, gel-type materials is required for several applications, especially in biomedical engineering domain. These include objectives of obtaining vascularized tissues and enclosed or subsurface microfluidic devices. However, presently there is no suitable manufacturing technology that can create such channels and networks in a gel structure. The advent of three-dimensional bioprinting has opened new possibilities for fabricating structures with complex geometries. However, application of this technique to fabricate internal hollow channels in viscoelastic material has not been yet explored to a great extent. In this article, we present the theoretical modeling/background of a proposed manufacturing paradigm through which hollow channels can be conveniently fabricated inside a gel structure. We propose that a tip connected to a robotic arm can be moved in X-, Y-, and Z-axis as per the desired design. The tip can be moved by a magnet or mechanical force. If the tip is further trailed with porous tube and moved inside the viscoelastic material, corresponding internal channels can be fabricated. To achieve this, however, force modeling to understand the forces that will be required to move the tip inside viscoelastic material should be known and understood. Therefore, in our first attempt, we developed the computational force modeling of the tip movement inside gels with different viscoelastic properties to create the channels.

Bioink formulations to ameliorate bioprinting-induced loss of cellular viability.

Extrusion bioprinting, the most affordable and convenient bioprinting modality, is also associated with high process-induced cell deaths. Mechanical stresses on the cells during pneumatic or piston extrusion generate excessive reactive oxygen species and activate apoptosis, inflammatory pathways in the cells. In this study, a bioink formulation is augmented with an antioxidant, N-acetyl cysteine (NAC) as a possible solution to abrogate the effect of bioprinting-associated cell survival losses. The NAC addition to bioinks did not affect the bioprinting process, shape fidelity, or the mechanical properties of the constructs to any large extent. However, the bioprinting process conducted at 0.30 MPa pressure and 410 µm nozzle inner diameter with bioinks of 3% w/v alginate, 105 cells/ml resulted in survival losses of up to 25% for MC3T3 cells. In contrast, NAC bioinks showed a significant (p < 0.01) improvement in day 1 cell survival (91%), while the enhancement in day 3 cell viability was still greater. It was further observed that the reactive oxygen species (ROS) load of bioprinted constructs was approximately 1.4 times higher compared to control, whereas NAC containing constructs reduced the ROS load at levels comparable to control samples. The effect on apoptosis and inflammation markers showed that NAC had a greater role in modulating apoptosis. It is concluded that the presented approach to preserve cell viability and functionality would be advantageous over other contemporary methods (like alterations in extrusion pressure, nozzle diameter, polymer concentration, etc.) as viability can be preserved without compromising the fabrication time or the resolution/mechanical properties of the constructs with this bioink formulation approach.