Yaxiong Liu

Rapid prototyping assisted surgery planning and custom implant design

Purpose – This paper aims to describe computer‐aided design and rapid prototyping (RP) systems for the preoperative planning and fabrication of custom‐made implant.Design/methodology/approach – A patient with mandible defect underwent reconstruction using custom‐made implant. 3D models of the patients skull are generated based on computed tomography image data. After evaluation of the 3D reconstructed image, it was identified that some bone fragment was moved due to the missing segment. During the implant design process, the correct position of the bone fragment was defined and the geometry of the custom‐made implant was generated based on mirror image technique and is fabricated by a RP machine. Surgical approach such as preoperative planning and simulation of surgical procedures was performed using the fabricated skull models and custom‐made implant.Findings – Results show that the stereolithography model provided an accurate tool for preoperative, surgical simulation.Research limitations/implications ...

Fabrication of Nature‐Inspired Microfluidic Network for Perfusable Tissue Constructs

A microreplication method is presented to transfer nature optimized vascular network of leaf venation into various synthetic matrixes. The biomaterial hydrogel with these microfluidic networks is proven to facilitate the growth of endothelial cells and simultaneously function as convection pathways to transport nutrients and oxygen in a pump-free bioreactor setup, which is crucial for the long-term viability of encapsulated cells.

Ice-template-induced silk fibroin-chitosan scaffolds with predefined microfluidic channels and fully porous structures.

Scaffold-based tissue engineering has made great progress in fabricating relatively simple tissues. One of the major challenges in creating thick complex organs is to achieve sufficient nutrient supply as well as uniform cell distribution in a three-dimensional (3D) scaffold. Here we employed microstructured ice templates to fabricate silk fibroin-chitosan (SF-CS) scaffolds with predefined microfluidic channels, open-pore surface and oriented porous structures. The effects of these structural organizations in ice-template-induced (ITI) scaffolds on nutrient delivery, cell seeding as well as cell growth were well investigated in comparison with that of polydimethylsiloxane-template-induced scaffolds. The ITI scaffolds exhibited better structural properties in promoting mass transport, facilitating uniform cell distribution and growth. The ITI scaffolds uniformly seeded with living cells could be further rolled up to form a thick tissue-engineered construct with predefined microfluidic channels. We envision that our ITI scaffolds can be potentially used to engineer thick prevascularized organs when the oriented porous structures are uniformly seeded with primary cells and the predefined microfluidic channels are incorporated with endothelial cells.

Human lower extremity joint moment prediction: A wavelet neural network approach

Joint moment is one of the most important factors in human gait analysis. It can be calculated using multi body dynamics but might not be straight forward. This study had two main purposes; firstly, to develop a generic multi-dimensional wavelet neural network (WNN) as a real-time surrogate model to calculate lower extremity joint moments and compare with those determined by multi body dynamics approach, secondly, to compare the calculation accuracy of WNN with feed forward artificial neural network (FFANN) as a traditional intelligent predictive structure in biomechanics. To aim these purposes, data of four patients walked with three different conditions were obtained from the literature. A total of 10 inputs including eight electromyography (EMG) signals and two ground reaction force (GRF) components were determined as the most informative inputs for the WNN based on the mutual information technique. Prediction ability of the network was tested at two different levels of inter-subject generalization. The WNN predictions were validated against outputs from multi body dynamics method in terms of normalized root mean square error (NRMSE (%)) and cross correlation coefficient (@r). Results showed that WNN can predict joint moments to a high level of accuracy (NRMSE 0.94) compared to FFANN (NRMSE 0.89). A generic WNN could also calculate joint moments much faster and easier than multi body dynamics approach based on GRFs and EMG signals which released the necessity of motion capture. It is therefore indicated that the WNN can be a surrogate model for real-time gait biomechanics evaluation.

Prediction of in vivo joint mechanics of an artificial knee implant using rigid multi-body dynamics with elastic contacts

Lower extremity musculoskeletal computational models play an important role in predicting joint forces and muscle activation simultaneously and are valuable for investigating functional outcomes of the implants. However, current computational musculoskeletal models of total knee replacement rarely consider the bearing surface geometry of the implant. Therefore, these models lack detailed information about the contact loading and joint motion which are important factors for evaluating clinical performances. This study extended a rigid multi-body dynamics simulation of a lower extremity musculoskeletal model to incorporate an artificial knee joint, based upon a novel force-dependent kinematics method, and to characterize the in vivo joint contact mechanics during gait. The developed musculoskeletal total knee replacement model integrated the rigid skeleton multi-body dynamics and the flexible contact mechanics of the tibiofemoral and patellofemoral joints. The predicted contact forces and muscle activations are compared against those in vivo measurements obtained from a single patient with good agreements for the medial contact force (root-mean-square error = 215 N, ρ = 0.96) and lateral contact force (root-mean-square error = 179 N, ρ = 0.75). Moreover, the developed model also predicted the motion of the tibiofemoral joint in all degrees of freedom. This new model provides an important step toward the development of a realistic dynamic musculoskeletal total knee replacement model to predict in vivo knee joint motion and loading simultaneously. This could offer a better opportunity to establish a robust virtual modeling platform for future pre-clinical assessment of knee prosthesis designs, surgical procedures and post-operation rehabilitation.

Fabrication of circular microfluidic network in enzymatically-crosslinked gelatin hydrogel.

It is a huge challenge to engineer vascular networks in vital organ tissue engineering. Although the incorporation of artificial microfluidic network into thick tissue-engineered constructs has shown great promise, most of the existing microfluidic strategies are limited to generate rectangle cross-sectional channels rather than circular vessels in soft hydrogels. Here we present a facile approach to fabricate branched microfluidic network with circular cross-sections in gelatin hydrogels by combining micromolding and enzymatically-crosslinking mechanism. Partially crosslinked hydrogel slides with predefined semi-circular channels were molded, assembled and in situ fully crosslinked to form a seamless and circular microfluidic network. The bonding strength of the resultant gelatin hydrogels was investigated. The morphology and the dimension of the resultant circular channels were characterized using scanning electron microscopy (SEM) and micro-computerized tomography (μCT). Computational fluid dynamic simulation shows that the fabrication error had little effect on the distribution of flow field but affected the maximum velocity in comparison with designed models. The microfluidic gelatin hydrogel facilitates the attachment and spreading of human umbilical endothelial cells (HUVECs) to form a uniform endothelialized layer around the circular channel surface, which successfully exhibited barrier functions. The presented method might provide a simple way to fabricate circular microfluidic networks in biologically-relevant hydrogels to advance various applications of in vitro tissue models, organ-on-a-chip systems and tissue engineering.

Layer-by-layer micromolding of natural biopolymer scaffolds with intrinsic microfluidic networks

A three-dimensional (3D) microfluidic network plays an important role in engineering thick organs. However, most of the existing methods are limited to mechanically robust synthetic biomaterials and only planar or simple microfluidic networks have been incorporated into soft natural biopolymers. Here we presented an automatic layer-by-layer micromolding strategy to reproducibly fabricate 3D microfluidic porous scaffolds directly from the aqueous solution of soft natural biopolymers. Process parameters such as the liquid volume for each layer and contact displacement were investigated to produce a structurally stable 3D microfluidic scaffold. Microscopic characterization demonstrated that the microfluidic channels were interconnected in 3D and successfully functioned as a convective pathway to transport a polymer solution. Endothelial cells grew relatively well in the porous microfluidic channels. It is envisioned that this method could provide an alternative way to reproducibly build complex 3D microfluidic networks into extracellular matrix-like scaffolds for the fabrication of soft vascularized organs.

The trend towards in vivo bioprinting

Bioprinting is one of several newly emerged tissue engineering strategies that hold great promise in alleviating of organ shortage crisis. To date, a range of living biological constructs have already been fabricated in vitro using this technology. However, an in vitro approach may have several intrinsic limitations regarding its clinical applicability in some cases. A possible solution is in vivo bioprinting, in which the de novo tissues/organs are to be directly fabricated and positioned at the damaged site in the living body. This strategy would be particularly effective in the treatment of tissues/organs that can be safely arrested and immobilized during bioprinting. Proof-of-concept studies on in vivo bioprinting have been reported recently, on the basis of which this paper reviews the current state-of-the-art bioprinting technologies with a particular focus on their advantages and challenges for the in vivo application.

The fabrication and cell culture of three-dimensional rolled scaffolds with complex micro-architectures

Cell cultures for tissue engineering are traditionally prepared on two-dimensional or three-dimensional scaffolds with simple pores; however, this limits mass transportation, which is necessary for cell viability and function. In this paper, an innovative method is proposed for fabricating porous scaffolds with designed complex micro-architectures. Channels devised by computer-aided design were used to simulate features of blood vessels in native rat liver. Rapid prototyping and microreplication were used to produce a negative polydimethylsiloxane mold, and then a planar porous scaffold with predefined microchannel parameters was obtained by freeze-drying a silk fibroin/gelatin solution of an optimized concentration. After seeding with rat primary hepatocytes, the planar scaffold was rolled up to build spatial channels. By reconstructing the three-dimensional channel model in the scaffold in the form of micro-computed topography data and observing the cross-sections of the scroll, we confirmed that the bent channels were still interconnected, with restricted deviations. A comparison of the primary hepatocyte culture in the scaffolds with and without the devised channels proved that our design influenced cell organization and improved cell survival and proliferation. This method can be used for the construction of complex tissues for implantation and for culturing cells in vitro for biological tests and observations.

Electrohydrodynamic printing: a potential tool for high-resolution hydrogel/cell patterning

ABSTRACT Electrohydrodynamic printing has gained increasing attentions to fabricate micro/nanoscale patterns in a controlled and cost-effective manner. However, most of the existing studies focus on printing tiny dried fibres, which limits its applications in high-resolution cell printing. Here we investigated the feasibility of using electrohydrodynamic printing to pattern microscale liquid filaments. Process parameters like stage moving speed and substrate resistance were optimised to stably print polyvinyl alcohol (PVA) liquid lines with the smallest line width of 37.4 μm. Complex patterns like XJTU logo with constant or variable line width were successfully printed by dynamically adjusting the moving speed. Fluorescent microparticles, with a similar diameter to living cells, were patterned in a one-by-one manner along with the PVA filaments. It is envisioned that the presented electrohydrodynamic printing method could be potentially used to high-resolution hydrogel/cell patterning for the studies of microscale cell–cell interactions or organ printing.