Inkjet-based Bioprinting Research Articles

Predictive Modeling of Droplet Formation Processes in Inkjet-Based Bioprinting

Additive manufacturing is driving major innovations in many areas such as biomedical engineering. Recent advances have enabled three-dimensional (3D) printing of biocompatible materials and cells into complex 3D functional living tissues and organs using bio-printable materials (i.e., bioink). Inkjet-based bioprinting fabricates the tissue and organ constructs by ejecting droplets onto a substrate. Compared with microextrusion-based and laser-assisted bioprinting, it is very difficult to predict and control the droplet formation process (e.g., droplet velocity and volume). To address this issue, this paper presents a new data-driven approach to predicting droplet velocity and volume in the inkjet-based bioprinting process. An imaging system was used to monitor the droplet formation process. To investigate the effects of polymer concentration, excitation voltage, dwell time, and rise time on droplet velocity and volume, a full factorial design of experiments (DOE) was conducted. Two predictive models were developed to predict droplet velocity and volume using ensemble learning. The accuracy of the two predictive models was measured using the root-mean-square error (RMSE), relative error (RE), and coefficient of determination (R2). Experimental results have shown that the predictive models are capable of predicting droplet velocity and volume with sufficient accuracy.

Recent advances in bioprinting techniques: approaches, applications and future prospects.

Bioprinting technology shows potential in tissue engineering for the fabrication of scaffolds, cells, tissues and organs reproducibly and with high accuracy. Bioprinting technologies are mainly divided into three categories, inkjet-based bioprinting, pressure-assisted bioprinting and laser-assisted bioprinting, based on their underlying printing principles. These various printing technologies have their advantages and limitations. Bioprinting utilizes biomaterials, cells or cell factors as a “bioink” to fabricate prospective tissue structures. Biomaterial parameters such as biocompatibility, cell viability and the cellular microenvironment strongly influence the printed product. Various printing technologies have been investigated, and great progress has been made in printing various types of tissue, including vasculature, heart, bone, cartilage, skin and liver. This review introduces basic principles and key aspects of some frequently used printing technologies. We focus on recent advances in three-dimensional printing applications, current challenges and future directions.

Bioprinting Technology: A Current State-of-the-Art Review

Bioprinting is an emerging technology for constructing and fabricating artificial tissue and organ constructs. This technology surpasses the traditional scaffold fabrication approach in tissue engineering (TE). Currently, there is a plethora of research being done on bioprinting technology and its potential as a future source for implants and full organ transplantation. This review paper overviews the current state of the art in bioprinting technology, describing the broad range of bioprinters and bioink used in preclinical studies. Distinctions between laser-, extrusion-, and inkjet-based bioprinting technologies along with appropriate and recommended bioinks are discussed. In addition, the current state of the art in bioprinter technology is reviewed with a focus on the commercial point of view. Current challenges and limitations are highlighted, and future directions for next-generation bioprinting technology are also presented.

Precise Control of Osteogenesis for Craniofacial Defect Repair

Success with bone morphogenetic protein-2 (BMP-2) has been widely reported in the osseous reconstruction of large calvarial defects. These efforts have required enormous doses of BMP-2 and are not sufficiently refined to facilitate the detail-oriented repair required for intricate craniofacial structures. We have previously shown that inkjet-based bioprinting technologies allow for precisely customized low-dose protein patterns to induce spatially regulated osteogenesis. Here, we investigate the importance of direct contact between bioprinted BMP-2 and the dura mater (a source of osteoprogenitors) in mediating calvarial healing. Five-millimeter osseous defects were trephinated in mouse parietal bones (N=8). Circular acellular dermal matrix (ADM) implants were prepared such that 1 semicircle of 1 face per implant was printed with BMP-2 bio-ink. These implants were then placed ink-toward (N=3) or ink-away (N=5) from the underlying dura mater. After 4 weeks, osteogenesis was assessed in each of the 4 possible positions (BMP-2-printed area toward dura, BMP-2-printed area away from dura, unprinted area toward dura, and unprinted area away from dura) by faxitron. The BMP-2-printed portion of the ADM generated bone covering an average of 66.5% of its surface area when it was face-down (printed surface directly abutting dura mater). By comparison, the BMP-2-printed portion of the ADM generated bone covering an average of only 21.3% of its surface area when it was face-up (printed surface away from dura). Similarly, the unprinted portion of the ADM generated an average of only 18.6% osseous coverage when face-down and 18.4% when face-up. We have previously shown that inkjet-based bioprinting has the potential to significantly enhance the role of regenerative therapies in craniofacial surgery. This technology affords the precise control of osteogenesis necessary to reconstruct this region's intricate anatomical architecture. In the present study, we demonstrate that direct apposition of BMP-2-printed ADM to a source of osteoprogenitor cells (in this case dura mater) is necessary for bio-ink-directed osteogenesis to occur. These results have important implications for the design of more complex bioprinted osseous structures.