Xiaofei Guan

Rapid Continuous Multimaterial Extrusion Bioprinting

The development of a multimaterial extrusion bioprinting platform is reported. This platform is capable of depositing multiple coded bioinks in a continuous manner with fast and smooth switching among different reservoirs for rapid fabrication of complex constructs, through digitally controlled extrusion of bioinks from a single printhead consisting of bundled capillaries synergized with programmed movement of the motorized stage.

Development of hydrogels for regenerative engineering

The aim of regenerative engineering is to restore complex tissues and biological systems through convergence in the fields of advanced biomaterials, stem cell science, and developmental biology. Hydrogels are one of the most attractive biomaterials for regenerative engineering, since they can be engineered into tissue mimetic 3D scaffolds to support cell growth due to their similarity to native extracellular matrix. Advanced nano‐ and micro‐technologies have dramatically increased the ability to control properties and functionalities of hydrogel materials by facilitating biomimetic fabrication of more sophisticated compositions and architectures, thus extending our understanding of cell‐matrix interactions at the nanoscale. With this perspective, this review discusses the most commonly used hydrogel materials and their fabrication strategies for regenerative engineering. We highlight the physical, chemical, and functional modulation of hydrogels to design and engineer biomimetic tissues based on recent achievements in nano‐ and micro‐technologies. In addition, current hydrogel‐based regenerative engineering strategies for treating multiple tissues, such as musculoskeletal, nervous and cardiac tissue, are also covered in this review. The interaction of multiple disciplines including materials science, cell biology, and chemistry, will further play an important role in the design of functional hydrogels for the regeneration of complex tissues.

Extrusion Bioprinting of Shear‐Thinning Gelatin Methacryloyl Bioinks

Bioprinting is an emerging technique for the fabrication of 3D cell-laden constructs. However, the progress for generating a 3D complex physiological microenvironment has been hampered by a lack of advanced cell-responsive bioinks that enable bioprinting with high structural fidelity, particularly in the case of extrusion-based bioprinting. Herein, this paper reports a novel strategy to directly bioprint cell-laden gelatin methacryloyl (GelMA) constructs using bioinks of GelMA physical gels (GPGs) achieved through a simple cooling process. Attributed to their shear-thinning and self-healing properties, the GPG bioinks can retain the shape and form integral structures after deposition, allowing for subsequent UV crosslinking for permanent stabilization. This paper shows the structural fidelity by bioprinting various 3D structures that are typically challenging to fabricate using conventional bioinks under extrusion modes. Moreover, the use of the GPG bioinks enables direct bioprinting of highly porous and soft constructs at relatively low concentrations (down to 3%) of GelMA. It is also demonstrated that the bioprinted constructs not only permit cell survival but also enhance cell proliferation as well as spreading at lower concentrations of the GPG bioinks. It is believed that such a strategy of bioprinting will provide many opportunities in convenient fabrication of 3D cell-laden constructs for applications in tissue engineering, regenerative medicine, and pharmaceutical screening.

Synergistic interplay between the two major bone minerals, hydroxyapatite and whitlockite nanoparticles, for osteogenic differentiation of mesenchymal stem cells

The inorganic part of human bone is mainly composed of hydroxyapatite (HAP: Ca10(PO4)6(OH)2) and whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) minerals, where the WH phase occupies up to 20-35% of total weight. These two bone minerals have different crystal structures and physicochemical properties, implying their distinguished role in bone physiology. However, until now, the biological significance of the presence of a certain ratio between HAP and WH in bone is unclear. To address this fundamental question, bone mimetic scaffolds are designed to encapsulate human mesenchymal stem cells (MSCs) for assessing their osteogenic activity depending on different ratios of HAP and WH. Interestingly, cellular growth and osteogenic differentiation are significantly promoted when MSCs are grown with a 3-1 ratio of HAP and WH nanoparticles, which is similar to bone. One of the reasons for this synergism between HAP and WH in hydrogel scaffolds is that, while WH nanoparticles can enhance osteogenic differentiation of MSCs compared to HAP, WH counterintuitively decreases the mechanical stiffness of nanocomposite hydrogels and hinders the osteogenic activity of cells. Taken together, these findings identify the optimal ratio between two major minerals in bone mimetic scaffolds to maximize the osteogenic differentiation of MSCs. STATEMENT OF SIGNIFICANCE Human bone minerals are composed of HAP and WH inorganic nanoparticles which have different material properties. However, the reason for the coexistence of HAP and WH in human bone is not fully identified, and HAP and WH composite biomaterial has not been utilized in the clinic. In this study, we have developed bone mimetic HAP and WH nanocomposite hydrogel scaffolds with various ratios. Importantly, we found out that HAP can promote the mechanical stiffness of the composite hydrogel scaffolds while WH can enhance the osteogenic activity of stem cells, which together induced synergism to maximize osteogenic differentiation of stem cells when mixed into 3-1 ratio that is similar to human bone.

Porous Electrospun Fibers with Self-Sealing Functionality: An Enabling Strategy for Trapping Biomacromolecules

Stimuli-responsive porous polymer materials have promising biomedical application due to their ability to trap and release biomacromolecules. In this work, a class of highly porous electrospun fibers is designed using polylactide as the polymer matrix and poly(ethylene oxide) as a porogen. Carbon nanotubes (CNTs) with different concentrations are further impregnated onto the fibers to achieve self-sealing functionality induced by photothermal conversion upon light irradiation. The fibers with 0.4 mg mL-1 of CNTs exhibit the optimum encapsulation efficiency of model biomacromolecules such as dextran, bovine serum albumin, and nucleic acids, although their photothermal conversion ability is slightly lower than the fibers with 0.8 mg mL-1 of CNTs. Interestingly, reversible reopening of the surface pores is accomplished with the degradation of PLA, affording a further possibility for sustained release of biomacromolecules after encapsulation. Effects of CNT loading on fiber morphology, structure, thermal/mechanical properties, degradation, and cell viability are also investigated. This novel class of porous electrospun fibers with self-sealing capability has great potential to serve as an enabling strategy for trapping/release of biomacromolecules with promising applications in, for example, preventing inflammatory diseases by scavenging cytokines from interstitial body fluids.

3D Printed Anchoring Sutures for Permanent Shaping of Tissues

Sutures are one of the most widely used devices for adhering separated tissues after injury or surgery. However, most sutures require knotting, which can create a risk of inflammation, and can act as mechanically weak points that often result in breakage and slipping. Here, an anchoring suture is presented with a design that facilitates its propagation parallel to the suturing direction, while maximizing its resistive force against the opposite direction of external force to lock its position in tissues. Different microstructures of suture anchors are systematically designed using orthogonal arrays, and selected based on shape factors associated with mechanical strength. 3D printing is used to fabricate different types of hollow microstructured suture anchors, and optimize their structure for the effective shaping of tissues. To define the structural design for fixing tissues, the maximum force required to pull 3D printed anchors in different directions is examined with tissues. The tissue reshaping function of suture anchors is further simulated ex vivo by using swine ear, nose, and skin, and bovine muscle tendon. This study provides advantages for building functional sutures that can be used for permanently reshaping tissues with enhanced mechanical strength, eliminating the need for knotting to improve surgical efficiency.