In the past few decades, additive manufacturing (AM) has been developed and applied as a cost-effective and versatile technique for the fabrication of geometrically complex objects in the medical industry. In this review, we discuss current advances of AM in medical applications for the generation of pharmaceuticals, medical implants, and medical devices. Oral and transdermal drugs can be fabricated by a variety of AM technologies. Different types of hard and soft clinical implants have also been realized by AM, with the goal of producing tissue-engineered constructs. In addition, medical devices used for diagnostics and treatment of various pathological conditions have been developed. The growing body of research on AM reveals its great potential in medical applications. The goal of this review is to highlight the usefulness and elucidate the current limitations of AM applications in the medical field.
Over the past 30 years, additive manufacturing (AM) has developed rapidly and has demonstrated great potential in biomedical applications. AM is a materials-oriented manufacturing technology, since the solidification mechanism, architecture resolution, post-treatment process, and functional application are based on the materials to be printed. However, 3D printable materials are still quite limited for the fabrication of bioimplants. In this work, 2D/3D AM materials for bioimplants are reviewed. Furthermore, inspired by Tai Chi, a simple yet novel soft/rigid hybrid 4D AM concept is advanced to develop complex and dynamic biological structures in the human body based on 4D printing hybrid ceramic precursor/ceramic materials that were previously developed by our group. With the development of multi-material printing technology, the development of bioimplants and soft/rigid hybrid biological structures with 2D/3D/4D AM materials can be anticipated.
Additive manufacturing plays a vital role in the food, mechanical, pharmaceutical, and medical fields. Within these fields, medical additive manufacturing has led to especially obvious improvements in medical instruments, prostheses, implants, and so forth, based on the advantages of cost-effectiveness, customizability, and quick manufacturing. With the features of precise structural control, high throughput, and good component manipulation, microfluidic techniques present distinctive benefits in medical additive manufacturing and have been applied in the areas of drug discovery, tissue engineering, and organs on chips. Thus, a comprehensive review of microfluidic techniques for medical additive manufacturing is useful for scientists with various backgrounds. Herein, we review recent progress in the development of microfluidic techniques for medical additive manufacturing. We evaluate the distinctive benefits associated with microfluidic technologies for medical additive manufacturing with respect to the fabrication of droplet/fiber templates with different structures. Extensive applications of microfluidic techniques for medical additive manufacturing are emphasized, such as cell guidance, three-dimensional (3D) cell culture, tissue assembly, and cell-based therapy. Finally, we present challenges in and future perspectives on the development of microfluidics for medical additive manufacturing.
Prostheses and orthoses are common assistive devices to meet the biomechanical needs of people with physical disabilities. The traditional fabrication approach for prostheses or orthoses is a materialwasting, time-consuming, and labor-intensive process. Additive manufacturing (AM) technology has advantages that can solve these problems. Many trials have been conducted in fabricating prostheses and orthoses. However, there is still a gap between the hype and the expected realities of AM in prosthetic and orthotic clinics. One of the key challenges is the lack of a systematic framework of integrated technologies with the AM procedure; another challenge is the need to design a prosthetic or orthotic product that can meet the requirements of both comfort and function. This study reviews the current state of application of AM technologies in prosthesis and orthosis fabrication, and discusses optimal design using computational methods and biomechanical evaluations of product performance. A systematic framework of the AM procedure is proposed, which covers the scanning of affected body parts through to the final designed adaptable product. A cycle of optimal design and biomechanical evaluation of products using finite-element analysis is included in the framework. A mature framework of the AM procedure and sufficient evidence that the resulting products show satisfactory biomechanical performance will promote the application of AM in prosthetic and orthotic clinics.
Due to their capability of fabricating geometrically complex structures, additive manufacturing (AM) techniques have provided unprecedented opportunities to produce biodegradable metallic implants— especially using Mg alloys, which exhibit appropriate mechanical properties and outstanding biocompatibility. However, many challenges hinder the fabrication of AM-processed biodegradable Mg-based implants, such as the difficulty of Mg powder preparation, powder splash, and crack formation during the AM process. In the present work, the challenges of AM-processed Mg components are analyzed and solutions to these challenges are proposed. A novel Mg-based alloy Mg–Nd–Zn–Zr alloy (JDBM) powder with a smooth surface and good roundness was first synthesized successfully, and the AM parameters for Mg-based alloys were optimized. Based on the optimized parameters, porous JDBM scaffolds with three different architectures (biomimetic, diamond, and gyroid) were then fabricated by selective laser melting (SLM), and their mechanical properties and degradation behavior were evaluated. Finally, the gyroid scaffolds with the best performance were selected for dicalcium phosphate dihydrate (DCPD) coating treatment, which greatly suppressed the degradation rate and increased the cytocompatibility, indicating a promising prospect for clinical application as bone tissue engineering scaffolds.
The development of an engineered non-contact multicellular coculture model that can mimic the in vivo cell microenvironment of human tissues remains challenging. In this study, we successfully fabricated a cell-container-like scaffold composed of β-tricalcium phosphate/hydroxyapatite (β-TCP/HA) bioceramic that contains four different pore structures, including triangles, squares, parallelograms, and rectangles, by means of three-dimensional (3D) printing technology. These scaffolds can be used to simultaneously culture four types of cells in a non-contact way. An engineered 3D coculture model composed of human bone-marrow-derived mesenchymal stem cells (HBMSCs), human umbilical vein endothelial cells (HUVECs), human umbilical vein smooth muscle cells (HUVSMCs), and human dermal fibroblasts (HDFs) with a spatially controlled distribution was constructed to investigate the individual or synergistic effects of these cells in osteogenesis and angiogenesis. The results showed that three or four kinds of cells cocultured in 3D cell containers exhibited a higher cell proliferation rate in comparison with that of a single cell type. Detailed studies into the cell–cell interactions between HBMSCs and HUVECs revealed that the 3D cell containers with four separate spatial structures enhanced the angiogenesis and osteogenesis of cells by amplifying the paracrine effect of the cocultured cells. Furthermore, the establishment of multicellular non-contact systems including three types of cells and four types of cells, respectively, cocultured in 3D cell containers demonstrated obvious advantages in enhancing osteogenic and angiogenic differentiation in comparison with monoculture modes and two-cell coculture modes. This study offers a new direction for developing a scaffold-based multicellular non-contact coculture system for tissue regeneration.
Complicated and large acetabular bone defects present the main challenges and difficulty in the revision of total hip arthroplasty (THA). This study aimed to explore the advantages of three-dimensional (3D) printing technology in the reconstruction of such acetabular bone defects. We retrospectively analyzed the prognosis of four severe bone defects around the acetabulum in three patients who were treated using 3D printing technology. Reconstruction of bone defect by conventional methods was difficult in these patients. In this endeavor, we used radiographic methods, related computer software such as Materialise's interactive medical image control system and Siemens NX software, and actual surgical experience to estimate defect volume, prosthesis stability, and installation accuracy, respectively. Moreover, a Harris hip score was obtained to evaluate limb function. It was found that bone defects could be adequately reconstructed using a 3D printing prosthesis, and its stability was reliable. The Harris hip score indicated a very good functional recovery in all three patients. In conclusion, 3D printing technology had a good therapeutic effect on both complex and large bone defects in the revision of THA. It was able to achieve good curative effects in patients with large bone defects.
Craniomaxillofacial reconstruction implants, which are extensively used in head and neck surgery, are conventionally made in standardized forms. During surgery, the implant must be bended manually to match the anatomy of the individual bones. The bending process is time-consuming, especially for inexperienced surgeons. Moreover, repetitive bending may induce undesirable internal stress concentration, resulting in fatigue under masticatory loading in vivo and causing various complications such as implant fracture, screw loosening, and bone resorption. There have been reports on the use of patient-specific 3D-printed implants for craniomaxillofacial reconstruction, although few reports have considered implant quality. In this paper, we present a systematic approach for making 3D-printed patient-specific surgical implants for craniomaxillofacial reconstruction. The approach consists of three parts: First, an easy-touse design module is developed using Solidworks® software, which helps surgeons to design the implants and the axillary fixtures for surgery. Design engineers can then carry out the detailed design and use finite-element simulation (FEM) to optimize the design. Second, the fabrication process is carried out in three steps: ① testing the quality of the powder; ② setting up the appropriate process parameters and running the 3D printing process; and ③ conducting post-processing treatments (i.e., heat and surface treatments) to ensure the quality and performance of the implant. Third, the operation begins after the final checking of the implant and sterilization. After the surgery, postoperative rehabilitation follow-up can be carried out using our patient tracking software. Following this systematic approach, we have successfully conducted a total of 41 surgical cases. 3D-printed patient-specific implants have a number of advantages; in particular, their use reduces surgery time and shortens patient recovery time. Moreover, the presented approach helps to ensure implant quality.
Primary hepatocytes (PHCs) are widely used in various fields, but the progressive deterioration of liver-specific features in vitro significantly limits their application. While the transcriptional regulation and whole cell proteome (WCP) of PHCs have been extensively studied, only a small number of studies have addressed the role of posttranslational modifications in this process. To elucidate the underlying mechanisms that induce dedifferentiation, we carried out parallel quantifications of the transcriptome, WCP, ubiquitinome, and phosphoproteome of rat PHCs after 0, 6, 12, 24, and 48 h of in vitro culture. Our data constitute a detailed proteomic analysis of dedifferentiated PHCs including 2196 proteins, 2056 ubiquitinated sites, and 4932 phosphorylated peptides. We revealed a low correlation between the transcriptome and WCP during dedifferentiation. A combined analysis of the ubiquitinome with the corresponding WCP indicated that the dedifferentiation of PHCs led to an increase in nondegradative K27 ubiquitination. Functional analysis of the altered phosphoproteins suggested a significant enrichment in ferroptosis. In all, 404 proteins with both ubiquitination and phosphorylation were identified to be involved in critical metabolic events. Furthermore, Ptbp1, Hnrpd, Hnrnpu, and Srrm2 were identified as hub genes. Taken together, our data provide new insights into proteome dynamics during PHC dedifferentiation and potential targets to inhibit the dedifferentiation process.
A non-pillar coal-mining technology with an automatically formed entry is proposed, which reduces the waste of coal resources and the underground entry drivage workload. Three key techniques in this technology cooperate to achieve automatic formation and retaining of the gob-side entry, and to realize non-pillar mining. Constant-resistance large deformation (CRLD) support ensures the stability of the entry roof; directional presplitting blasting (DPB) separates the entry roof and the gob roof; and a blocking-gangue support system (BGSS) integrates the caved rock material as an effective entry rib. An industrial test was conducted to verify the engineering effects of these key techniques. The field application results showed that the retained entry was under the pressure-relief zone due to the broken-expansion nature of the caved rock mass within the DPB height. After going through a provisional dynamic pressure-bearing zone, the retained entry entered the stability zone. The final stable entry meets the requirements of safety and production. The research results demonstrate the good engineering applicability of this technology. By taking the framework of the technology design principles into consideration and adjusting the measures according to different site conditions, it is expected that the proposed non-pillar coal-mining technology can be popularized on a large scale.