Hyaluronic acid (HA) is one of nature's most versatile and fascinating macromolecules. Being an essential component of the natural extracellular matrix (ECM), HA plays an important role in a variety of biological processes. Inherently biocompatible, biodegradable and non-immunogenic, HA is an attractive starting material for the construction of hydrogels with desired morphology, stiffness and bioactivity. While the interconnected network extends to the macroscopic level in HA bulk gels, HA hydrogel particles (HGPs, microgels or nanogels) confine the network to microscopic dimensions. Taking advantage of various scaffold fabrication techniques, HA hydrogels with complex architecture, unique anisotropy, tunable viscoelasticity and desired biologic outcomes have been synthesized and characterized. Physical entrapment and covalent integration of hydrogel particles in a secondary HA network give rise to hybrid networks that are hierarchically structured and mechanically robust, capable of mediating cellular activities through the spatial and temporal presentation of biological cues. This review highlights recent efforts in converting a naturally occurring polysaccharide to drug releasing hydrogel particles, and finally, complex and instructive macroscopic networks. HA-based hydrogels are promising materials for tissue repair and regeneration.

The current investigation aimed to develop a biomimetic, three-dimensional (3D) culture system for poorly adherent bone metastatic prostate cancer cells (C4-2B) for use as an in vitro platform for anti-cancer drug screening. To this end, hyaluronic acid (HA) derivatives carrying complementary aldehyde (HAALD) and hydrazide (HAADH) groups were synthesized and characterized. In situ encapsulation of C4-2B cells was achieved by simple mixing of HAALD and HAADH in the presence of the cells. Unlike two-dimensional (2D) monolayer culture in which cells adopt an atypical spread morphology, cells residing in the HA matrix formed distinct clustered structures which grew and merged, reminiscent of real tumors. Anti-cancer drugs added to the media surrounding the cell/gel construct diffused into the gel and killed the embedded cells. The HA hydrogel system was used successfully to test the efficacy of anti-cancer drugs including camptothecin, docetaxel, and rapamycin, alone and in combination, including specificity, dose and time responses. Responses of cells to anti-neoplastics differed between the 3D HA hydrogel and 2D monolayer systems. We suggest that the data obtained from 3D HA systems is superior to that from conventional 2D monolayers as the 3D system better reflects the bone metastatic microenvironment of the cancer cells.

This review focuses on current tissue engineering strategies for promoting vascularized bone regeneration. We review the role of angiogenic growth factors in promoting vascularized bone regeneration and discuss the different therapeutic strategies for controlled/sustained growth factor delivery. Next, we address the therapeutic uses of stem cells in vascularized bone regeneration. Specifically, this review addresses the concept of co-culture using osteogenic and vasculogenic stem cells, and how adipose derived stem cells compare to bone marrow derived mesenchymal stem cells in the promotion of angiogenesis. We conclude this review with a discussion of a novel approach to bone regeneration through a cartilage intermediate, and discuss why it has the potential to be more effective than traditional bone grafting methods.

the printing process. Previously, patterning of liquid metals by direct writing [ 9 ] and fi lling predefi ned microchannels has been demonstrated. [ 10-12 ] Furthermore, the use of liquid metal as conductors, [ 13,14 ] capacitors, [ 15 ] and antennas [ 16-24 ] has been shown. The illustrated circuit and sensor applications include embedded elastomer conductors, [ 13 ] hyperelastic pressure sensors, [ 10 ] stretchable radiation sensors, [ 17 ] passive wireless sensors, [ 11 ] deformable and tunable fl uidic antennas, [ 25 ] and tac-tile interfaces. [ 26 ] Given these advances, 3D printing can now be exploited to develop 3D electronic systems embedded within printed objects that facilitate personalized sensing and actuation function-alities. To illustrate this capability, we particularly demonstrate 3D printing of two fully integrated objects that deliver various sensing, actuation, and signal processing operations. These objects embed liquid metal-based passive/active components and commercially available silicon integrated circuits (ICs) to achieve the envisioned functionalities. The fi rst object demonstrates the capability of 3D printing approach to embed multi-layer electronic circuit boards within 3D structures. The second object demonstrates the application of 3D printing process to deliver wearable platforms that are specifi cally tailored to an individual's body and needs. Specifi cally, a form-fi tting glove is developed with embedded programmable heater, temperature sensor, and the associated control electronics for thermothera-peutic treatment. The process enables assembly of electronic components into complex 3D architectures and provides a new platform for creating personalized smart objects. As exemplifi ed in Figure 1 a, conductive channels are printed within an object (e.g., a glove) in various confi gurations to realize 3D liquid-state sensors, actuators, and circuit components (resistors, capacitors, and antennas). These components can be tunably printed within both stretchable and rigid sub-strates and can provide standalone functionalities. The channels are also used as interconnects to integrate readily available silicon IC chips and realize fully embedded systems inside the printed object. Integration of silicon IC chips enables advanced circuit functionalities that would not have been achieved otherwise by 3D printed liquid-state components alone. Figure 1 be illustrates the corresponding fabrication scheme. First, as shown in Figure 1 b, a base substrate, containing microchan-nels and slots for the integrated components, is fabricated by a 3D printer (MakerGear and Leapfrog). Second, the microchan-nels are injected with liquid metal to form the liquid-based circuit components, devices, and interconnects (Figure 1 c). Third, IC chips and other solid state electronic components including discrete resistors and capacitors are embedded within the Aligned with the vision of "Internet of Things," it is expected that the number of interconnected devices, equipped with sensing and actuation funct...