The concept of in situ 3D bio-printing was previously reported, while its realization has still encountered with several difficulties. The present study aimed to report robotic-assisted in situ 3D bio-printing technology for cartilage regeneration, and explore its potential in clinical application. A six-degree-of-freedom (6-DOF) robot was introduced in this study, and a fast tool center point (TCP) calibration method was developed to improve printing accuracy. The bio-ink consisted of hyaluronic acid methacrylate and acrylate-terminated 4-armed polyethylene glycol was employed as well. The in vitro experiment was performed on a resin model to verify the printing accuracy. The in vivo experiment was conducted on rabbits to evaluate the cartilage treatment capability. According to our results, the accuracy of the robot could be notably improved, and the error of printed surface was less than 30 μm. The osteochondral defect could be repaired during about 60 s, and the regenerated cartilage in hydrogel implantation and in situ 3D bio-printing groups demonstrated the same biomechanical and biochemical performance. We found that the cartilage injury could be treated by using this method. The robotic-assisted in situ 3D bio-printing is highly appropriate for improving surgical procedure, as well as promoting cartilage regeneration.

Three-dimensional (3D) printing is a rapidly emerging technology that promises to transform tissue engineering into a commercially successful biomedical industry. However, the use of robotic bioprinters alone is not sufficient for disease treatment. This study aimed to report the combined application of 3D scanning and 3D printing for treating bone and cartilage defects. Three different kinds of defect models were created to mimic three orthopedic diseases: large segmental defects of long bones, free-form fracture of femoral condyle, and International Cartilage Repair Society grade IV chondral lesion. Feasibility of in situ 3D bioprinting for these diseases was explored. The 3D digital models of samples with defects and corresponding healthy parts were obtained using high-resolution 3D scanning. The Boolean operation was used to achieve the shape of the defects, and then the target geometries were imported in a 3D bioprinter. Two kinds of photopolymerized hydrogels were synthesized as bioinks. Finally, the defects of bone and cartilage were restored perfectly in situ using 3D bioprinting. The results of this study suggested that 3D scanning and 3D bioprinting could provide another strategy for tissue engineering and regenerative medicine.

Hydrogels, consisting of hydrophilic polymers, can be used as films, scaffolds, nanoparticles and drug carriers. They are one of the hot research topics in material science and tissue engineering and are widely used in the field of biomedical and biological sciences. Researchers are seeking for a type of material that is similar to human tissues and can partially replace human tissues or organs. The hydrogel has brought possibility to solve this problem. It has good biocompatibility and biodegradability. After entering the body, it does not cause immune and toxic reactions. The degradation time can be controlled, and the degradation products are nontoxic and nonimmunogenic; the final metabolites can be excreted outside the body. Owing to the lack of blood vessels and poor migration ability of chondrocytes, the self-healing ability of damaged cartilage is limited. Tissue engineering has brought a new direction for the regeneration of cartilage. Drug carriers and scaffolds made of hydrogels are widely used in cartilage tissue engineering. The present review introduces the natural hydrogels, which are often used for cartilage tissue engineering with respect to synthesis, modification and application methods. This review introduces the natural hydrogels that are often used in cartilage tissue engineering with respect to synthesis, modification and application methods. Furthermore, the essential concepts and recent discoveries were demonstrated to illustrate the achievable goals and the current limitations. In addition, we propose the putative challenges and directions for the use of natural hydrogels in cartilage regeneration.

The graded porous structures were designed using triply periodic minimal surfaces models to mimic the biomechanical properties of bone. The mechanical properties and bone formation ability were evaluated to explore the feasibility of the design method in bone tissue engineering. The scaffolds were designed using a P-surface with different pore sizes. All materials were fabricated using 3D printing technology and the mechanical properties were tested by an electronic universal testing device. The biomechanical properties were then analyzed by finite element method, while the ontogenesis of the material in vivo was examined by implanting the scaffolds for five weeks in pigs. According to the obtained results, the pore size ranged between 100 μm to about 700 μm and porosity were around 49.54%. The graded porous architectures can decrease the stiffness of implants and reduce the stress shielding effect. In addition, these porous structures can stimulate bone ingrowth and achieve a stable interface between implants and surrounding bone tissues after 5 weeks' implantation. The micro-CT results also demonstrated the obviously bone formation around all the porous structures. To sum up, the triply periodic minimal surfaces based graded porous structure is effective in decreasing the stress shielding effect, promoting early osteogenesis and osteointegration. This is the first research to explore the effect of this kind of porous structures on bone formation in vivo where the obtained results supported the previous theoretical research on the application potential in bone tissue engineering. Porous architecture designed using triply periodic minimal surface models can achieve gradually changed pore size and appropriate porosity for bone regeneration. This kind of structure can mimic the Young's modulus of natural bone tissue, improve the stress transmission capability and dismiss the stress shielding effect. It also can stimulate the early bone integration in vivo and enhance the binding force between bone and implants, which may bring a new design method for orthopaedic implants and their surface structure.

The traditional clinical treatment of long segmental bone defects usually requires multiple operations and depends on donor availability. The 3D bio-printing technology constitutes a great potential therapeutic tool for such an injury. However, in situ 3D bio-printing remains a major challenge. In this study, we report the repair of long segmental bone defects by in situ 3D bio-printing using a robotic manipulator 3D printer in a swine model. We systematically optimized bio-ink gelation under physiological conditions to achieve desirable mechanical properties suitable for bone regeneration, and a D-H kinematic model was used to improve printing accuracy to 0.5 mm. These technical improvements allowed the repair of long segmental defects generated on the right tibia of pigs using 3D bio-printing within 12 min. The 3D bio-printing group showed improved treatment effects after 3 months. These findings indicated that robotic in situ 3D bio-printing is promising for direct clinical application.

The applications of robotics to the rehabilitation training of neuromuscular impairments have received increasing attention due to their promising prospects. The effectiveness of robot-assisted training directly depends on the control strategy applied in the therapy program. This paper presents an upper extremity exoskeleton for the functional recovery training of disabled patients. A minimal-intervention-based admittance control strategy is developed to induce the active participation of patients and maximize the use of recovered motor functions during training. The proposed control strategy can transit among three control modes, including human-conduct mode, robot-assist mode, and motion-restricted mode, based on the real-time position tracking errors of the end-effector. The human-robot interaction in different working areas can be modulated according to the motion intention of patient. Graphical guidance developed in Unity-3-D environment is introduced to provide visual training instructions. Furthermore, to improve training performance, the controller parameters should be adjusted in accordance with the hemiplegia degree of patients. For the patients with severe paralysis, robotic assistance should be increased to guarantee the accomplishment of training. For the patients recovering parts of motor functions, robotic assistance should be reduced to enhance the training intensity of effected limb and improve therapeutic effectiveness. The feasibility and effectiveness of the proposed control scheme are validated via training experiments with two healthy subjects and six stroke patients with different degrees of hemiplegia.