SIRIUS, Ultra-Scintillating Upconversion Breast Implant for Remote Orthotopic Photodynamic Therapy.

Present day strategies for delivery of wireless photodynamic therapy (PDT) to deep-seated targets are limited by the inadequacy of irradiance and insufficient therapeutic depth. Here we report the design and preclinical validation of a flexible wireless upconversion nanoparticle (UCNP) implant (SIRIUS) that is capable of large field, high intensity illumination for PDT of deep-seated tumors. The implant achieves this by incorporating submicrometer core-shell-shell NaYF4 UCNPs into its design, which significantly enhances upconversion efficiency and mitigates light loss from surface quenching. We demonstrate the efficacy of SIRIUS UCNP implant mediated PDT in preclinical breast cancer disease models. In our in vitro experiments, SIRIUS directed 5-Aminolevulinic Acid (5-ALA) based wireless PDT leads to significant reactive oxygen species (ROS) generation and tumor apoptosis in hormonal receptor+/HER2+ (MCF7) and triple-negative (MDA-MB-231) breast cancer cell lines. In our in vivo rodent model, SIRIUS-driven PDT is shown to be significant in regressing tumors when applied to orthotopically inoculated breast tumors. Following successful preclinical validation, we also describe a clinical prototype of UCNP breast implant with potential dual cosmetic and onco-therapeutic functions. SIRIUS is an upconversion breast implant for wireless PDT that fulfils all the design prerequisites necessary for seamless clinical translation.

The effect of chondroitin sulfate concentration and matrix stiffness on chondrogenic differentiation of mesenchymal stem cells.

Chondroitin sulfate (CS), a glycosaminoglycan of native cartilage, has shown its potential in promoting chondrogenesis of mesenchymal stem cells (MSCs), whereas the effect of matrix stiffness in a CS-containing 3D environment on chondrogenesis is still poorly understood. Herein, this study aimed at assessing the effect of CS concentration and stiffness of CS-containing hydrogels on the chondrogenesis of MSCs. Hydrogels composed of 6% (w/v) gelatin methacryloyl (GelMA) and three concentrations, i.e., 4%, 6%, or 10% (w/v), of methacrylated chondroitin sulfate (CSMA) were prepared. The hydrogels of each composition were prepared with two stiffness values (33.36 ± 8.25 kPa vs. 8.42 ± 2.83 kPa). Physical characterization showed similar microporous structures among the six groups, higher swelling ratios and faster degradation in the soft hydrogel groups. MSCs were encapsulated in the six groups of hydrogels and they underwent 28-day chondrogenic differentiation. The cell viability in each group on day 1 was similar and most cells exhibited a round shape without spreading. Afterwards, cellular protrusions in soft hydrogels remained filopodium-like from day 14 to day 28, while most protrusions were lamellipodium-like in stiff hydrogels on day 14 and then transformed into a spherical shape on day 28. The expression of chondrogenic markers analysed by real-time qPCR and immunohistochemical staining demonstrated that the optimal CS concentration for chondrogenesis was 6% (w/v) regardless of the stiffness of hydrogels. In addition, with the same CSMA concentration, the trend was observed that the stiff hydrogels supported superior chondrogenesis of MSCs compared to the soft hydrogel. To summarize, this study presents an advancement in the optimization of CSMA concentration and stiffness of hydrogels for chondrogenesis. In the CSMA/GelMA hydrogel, 6% (w/v) CSMA with an initial Young's modulus around 33 kPa was recommended for cartilage tissue engineering.

Stretchable and Self-Adhesive PEDOT:PSS Blend with High Sweat Tolerance as Conformal Biopotential Dry Electrodes.

Dry epidermal electrodes that can always form conformal contact with skin can be used for continuous long-term biopotential monitoring, which can provide vital information for disease diagnosis and rehabilitation. But, this application has been limited by the poor contact of dry electrodes on wet skin. Herein, we report a biocompatible fully organic dry electrode that can form conformal contact with both dry and wet skin even during physical movement. The dry electrodes are prepared by drop casting an aqueous solution consisting of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS), poly(vinyl alcohol) (PVA), tannic acid (TA), and ethylene glycol (EG). The electrodes can exhibit a conductivity of 122 S cm-1 and a mechanical stretchability of 54%. Moreover, they are self-adhesive to not only dry skin but also wet skin. As a result, they can exhibit a lower contact impedance to skin than commercial Ag/AgCl gel electrodes on both dry and sweat skins. They can be used as dry epidermal electrodes to accurately detect biopotential signals including electrocardiogram (ECG) and electromyogram (EMG) on both dry and wet skins for the users at rest or during physical movement. This is the first time to demonstrate dry epidermal electrodes self-adhesive to wet skin for accurate biopotential detection.

Silk Fibroin as a Bioink - A Thematic Review of Functionalization Strategies for Bioprinting Applications.

Bioprinting is an emerging tissue engineering technique that has attracted the attention of researchers around the world, for its ability to create tissue constructs that recapitulate physiological function. While the technique has been receiving hype, there are still limitations to the use of bioprinting in practical applications, much of which is due to inappropriate bioink design that is unable to recapitulate complex tissue architecture. Silk fibroin (SF) is an exciting and promising bioink candidate that has been increasingly popular in bioprinting applications because of its processability, biodegradability, and biocompatibility properties. However, due to its lack of optimum gelation properties, functionalization strategies need to be employed so that SF can be effectively used in bioprinting applications. These functionalization strategies are processing methods which allow SF to be compatible with specific bioprinting techniques. Previous literature reviews of SF as a bioink mainly focus on discussing different methods to functionalize SF as a bioink, while a comprehensive review on categorizing SF functional methods according to their potential applications is missing. This paper seeks to discuss and compartmentalize the different strategies used to functionalize SF for bioprinting and categorize the strategies for each bioprinting method (namely, inkjet, extrusion, and light-based bioprinting). By compartmentalizing the various strategies for each printing method, the paper illustrates how each strategy is better suited for a target tissue application. The paper will also discuss applications of SF bioinks in regenerating various tissue types and the challenges and future trends that SF can take in its role as a bioink material.

Bone marrow mesenchymal stem cells with low dose bone morphogenetic protein 2 enhances scaffold-based spinal fusion in a porcine model.

High doses bone morphogenetic protein 2 (BMP-2) have resulted in a series of complications in spinal fusion. We previously established a polyelectrolyte complex (PEC) carrier system that reduces the therapeutic dose of BMP-2 in both rodent and porcine spinal fusion models. This study aimed to evaluate the safety and efficacy of the combination of bone marrow mesenchymal stem cells (BMSCs) and low dose BMP-2 delivered by PEC for bone regeneration in a porcine model of anterior lumbar interbody spinal fusion (ALIF) application. Six Yorkshire pigs underwent a tri-segmental (L2/L3; L3/L4; L4/L5) ALIF in four groups, namely: (a) BMSCs + 25 µg BMP-2/PEC (n = 9), (b) 25 µg BMP-2/PEC (n = 3), (c) BMSCs (n = 3), and (d) 50 µg BMP-2/absorbable collagen sponge (n = 3). Fusion outcomes were evaluated by radiography, biomechanical testing, and histological analysis after 12 weeks. Mean radiographic scores at 12 weeks were 2.7, 2.0, 1.0, and 1.0 for Groups 1 to 4, respectively. µ-CT scanning, biomechanical evaluation, and histological analysis demonstrated solid fusion and successful bone regeneration in Group 1. In contrast, Group 2 showed inferior quality and slow rate of fusion, and Groups 3 and 4 failed to fuse any of the interbody spaces. There was no obvious evidence of seroma formation, implant rejection, or any other complications in all groups. The results suggest that the combination of BMSCs and low dose BMP-2/PEC could further lower down the effective dose of the BMP-2 and be used as a bone graft substitute in the large animal ALIF model.

Osteochondral tissue engineering: Perspectives for clinical application and preclinical development.

The treatment of osteochondral defects (OCD) remains challenging. Among currently available surgical treatments for OCDs, scaffold-based treatments are promising to regenerate the osteochondral unit. However, there is still no consensus regarding the clinical effectiveness of these scaffold-based therapies for OCDs. Previous reviews have described the gradient physiological characteristics of osteochondral tissue and gradient scaffold design for OCD, tissue engineering strategies, biomaterials, and fabrication technologies. However, the discussion on bridging the gap between the clinical need and preclinical research is still limited, on which we focus in the present review, providing an insight into what is currently lacking in tissue engineering methods that failed to yield satisfactory outcomes, and what is needed to further improve these techniques. Currently available surgical treatments for OCDs are firstly summarized, followed by a comprehensive review on experimental animal studies in recent 5 years on osteochondral tissue engineering. The review will then conclude with what is currently lacking in these animal studies and the recommendations that would help enlighten the community in developing more clinically relevant implants. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This review is attempting to summarize the lessons from clinical and preclinical failures, providing an insight into what is currently lacking in TE methods that failed to yield satisfactory outcomes, and what is needed to further improve these implants.

Conductive polypyrrole-encapsulated silk fibroin fibers for cardiac tissue engineering.

Polypyrrole (PPy) has been utilized in smart scaffolds to improve the functionality of the engineered cardiac tissue. Compared to the commonly used aqueous coating, here, PPy was blended into silk fibroin (SF) solution to electrospin conductive PPy-encapsulated SF nanofibers. Combinations of various SF concentrations (5%, 7%, and 12%) and different PPy-to-SF ratios (15:85, 30:70, and 40:60) were compared. PPy reduced the fiber diameter (0.431 ± 0.060 µm), better-mimicking the myocardium fibrils. Conductive mats with 7% SF showed the closest mechanical properties (1.437 ± 0.044 MPa) to the native myocardium; meanwhile, a PPy-to-SF ratio of 15:85 exhibited sufficient electrical conductivity for cardiomyocytes (CMs). In vitro studies using three different types of CM demonstrated that the hybrid mats support CM contraction. Primary neonatal rat CMs on the mat with a PPy-to-SF ratio of 15:85 were elongated and orientated anisotropically with locally organized sarcomeric striations. By contrast, human-induced pluripotent stem cell derived-CMs on the mat with a PPy-to-SF ratio of 30:70 exhibited the strongest contractions. Contraction synchrony was further improved by external stimulation. Taken together, these findings indicated the great potential of the PPy-encapsulated SF electrospun mat for cardiac tissue engineering.

Fabrication of 3D-Printed Ceramic Structures for Portable Solar Desalination Devices.

This paper proposes the fabrication process of the first fully 3D-printed ceramic core structures for portable solar desalination devices optimized to tackle water scarcity from an energy and sustainability perspective. Robocasting, a 3D printing technique, is utilized to fabricate a fully ceramic structure of an integrated solar absorber/thermal insulator/water transporter based on the two-layered structure of modified graphene on silica (MG@Silica) and the porous silica structure. Robocasting has demonstrated its flexibility in tailoring structural designs, combining nanopores and microchannels that exhibit uniform water transport delivery and thermal insulation. This portable device can be used immediately to collect fresh drinking water without an additional setup. It possesses a water evaporation rate of 2.4 kg m-2 h-1 with a drinking water production capacity of 0.5 L m-2 h-1. This novel device has shown excellent ion rejection ability, with the collected water meeting the World Health Organization (WHO) drinking water standards.

Pore size modulates in vitro osteogenesis of bone marrow mesenchymal stem cells in fibronectin/gelatin coated silk fibroin scaffolds.

Porous scaffolds have been widely used for bone tissue engineering (BTE), and the pore structure of scaffolds plays an important role in osteogenesis. Silk fibroin (SF) is a favorable biomaterial for BTE due to its excellent mechanical property, biocompatibility, and biodegradation, but the lack of cell attachment sites in SF chemical structure resulted in poor cell-material interactions. In this study, SF scaffolds were coated with fibronectin/gelatin (Fn/G) to improve cell adhesion. Furthermore, the effect of pore size in Fn/G coated SF scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were investigated in vitro. Scaffolds with average pore diameters of 384.52, 275.23, and 173.8 µm were prepared by salt leaching method, labelled as Large, Medium, and Small group. Porcine BMSCs were seeded on scaffolds and cultured in osteogenic medium for 21 days to evaluate cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition, gene expression of osteogenic markers, and histological performance. The results showed Fn/G coating effectively improved cell adhesion on SF scaffolds. Cell metabolic rate in each group increased significantly with time, but there was no statistical difference at each time point among the three groups. On day 21, ALP/DNA and calcium/DNA in the Small group were significantly higher than those in the Large group. Among the three pore sizes, the Small group showed higher mRNA expression of COl I on day 7, OPN on day 14, and OCN on day 21. Immunohistochemical staining on day 21 showed that Col I and OCN in Small group were more highly expressed. In conclusion, the Fn/G coated SF scaffolds with a mean pore diameter of 173.8 µm was optimal for osteogenic differentiation of BMSC in vitro.

Improving the handling properties and long-term stability of polyelectrolyte complex by freeze-drying technique for low-dose bone morphogenetic protein 2 delivery.

A variety of controlled release carriers for bone morphogenetic protein 2 (BMP-2) delivery have been developed and tested in animal models. An alginate-based polyelectrolyte complex (PEC) for controlled release of low-dose BMP-2 has shown promising results in preclinical research. However, the poor handling properties and long-term stability of PEC need to be improved for translational applications. This study aimed to address these limitations of alginate-based PEC by employing a freeze-drying technique. The size and structure of freeze-dried PEC (FD-PEC) were maintained with the addition of a cryoprotectant, trehalose. The release profile of BMP-2 from FD-PEC was similar to that of freshly prepared PEC. In vitro bioactivity analysis of the released BMP-2 showed that the carrier performance of PEC was not compromised by freeze-drying up to three-month storage at room temperature. BMP-2-bound FD-PEC induced comparable bone formation to that using freshly prepared regular PEC in a rat posterolateral spinal fusion model. These results suggest that FD-PEC is capable of delivering low-dose BMP-2 and could be developed as an off-the-shelf product for translational applications. The simplicity of this preservation method provides promise for the translational application of PEC.

Polypyrrole-Incorporated Conducting Constructs for Tissue Engineering Applications: A Review.

Conductive polymers have recently attracted interest in biomedical applications because of their excellent intrinsic electrical conductivity and satisfactory biocompatibility. Polypyrrole (PPy) is one of the most popular among these conductive polymers due to its high conductivity under physiological conditions, and it can be chemically modified to allow biomolecules conjugation. PPy has been used in fabricating biocompatible stimulus-responsive scaffolds for tissue engineering applications, especially for repair and regeneration of electroactive tissues, such as the bone, neuron, and heart. This review provides a comprehensive overview of the basic properties and synthesis methods of PPy, as well as a summary of the materials that have been integrated with PPy. These composite scaffolds are comparatively evaluated with regard to their mechanical properties, biocompatibility, and usage in tissue engineering.

Synergistic Effect of NELL-1 and an Ultra-Low Dose of BMP-2 on Spinal Fusion.

Bone morphogenetic protein 2 (BMP-2) is widely used in spinal fusion but it can cause adverse effects such as ectopic bone and adipose tissue in vivo. Neural epidermal growth factor like-like molecule-1 (NELL-1) has been shown to suppress BMP-2-induced adverse effects. However, no optimum carriers that control both NELL-1 and BMP-2 releases to elicit long-term bioactivity have been developed. In this study, we employed polyelectrolyte complex (PEC) as a control release carrier for NELL-1 and BMP-2. An ultra-low dose of BMP-2 synergistically functioned with NELL-1 on bone marrow mesenchymal stem cells osteogenic differentiation with greater mineralization in vitro. The osteoinductive ability of NELL-1 and an ultra-low dose of BMP-2 in PEC was investigated in rat posterolateral spinal fusion. Our results showed increased fusion rate, bone architecture, and improved bone stiffness at 8 weeks after surgery in the combination groups compared with NELL-1 or BMP-2 alone. Moreover, the formation of ectopic bone and adipose tissue was negligible in all the PEC groups. In summary, dual delivery of NELL-1 and an ultra-low dose of BMP-2 in the PEC control release carrier has greater fusion efficiency compared with BMP-2 alone and could potentially be a better alternative to the currently used BMP-2 treatments for spinal fusion. Impact Statement In this study, polyelectrolyte complex was used to absorb neural epidermal growth factor like-like molecule-1 (NELL-1) and bone morphogenetic protein 2 (BMP-2) to achieve controlled dual release. The addition of NELL-1 significantly reduced the effective dose of BMP-2 to 2.5% of its conventional dose in absorbable collagen sponge, to produce solid spinal fusion without significant adverse effects. This study was the first to identify the efficacy of combination NELL-1 and BMP-2 in a control release carrier in spinal fusion, which could be potentially used clinically to increase fusion rate and avoid the adverse effects commonly associated with conventional BMP-2.

Bone Regeneration by Controlled Release of Bone Morphogenetic Protein-2: A Rabbit Spinal Fusion Chamber Molecular Study.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used in spine fusion surgery. However, high doses of rhBMP-2 delivered with absorbable collagen sponge (ACS) have led to inflammation-related adverse conditions. Polyelectrolyte complex (PEC) control release carrier can substantially reduce the rhBMP-2 dose and complication without compromising fusion. The molecular events underlying controlled release and their effects on spinal fusion remain unknown. In this study, a rabbit interbody spinal fusion chamber was designed to provide a controlled environment for profiling molecular events during the fusion process. Study groups included Group 1, PEC with 100 µg rhBMP-2; Group 2, ACS with 100 µg rhBMP-2; Group 3, ACS with 300 µg rhBMP-2; Group 4, autologous bone graft; and Group 5, empty chamber. Manual palpation, microcomputed tomography, and histological analysis showed that Group 1 and 3 achieved bone fusion, while the other groups showed no signs of fusion. Gene expression profiling showed robust induction of osteogenic markers in Groups 1 and 3, with modulated early induction of inflammatory genes in the PEC group. Delivery of 100 µg rhBMP-2 with ACS (Group 2) resulted in less upregulation of osteogenic genes, increased inflammatory genes expression, and upregulation of osteoclastic genes compared to Group 1. These results suggest that the manner of BMP-2 release at the interbody spinal defect site could dictate the balance of in-situ osteogenic and antiosteogenic activities, affecting fusion outcomes. The molecular evidence supports PEC for sustained release of BMP-2 for spinal interbody fusion, and the feasibility of employing this novel interbody spinal fusion chamber for future molecular studies. Impact Statement A radiolucent rabbit interbody spinal fusion chamber was developed to study the molecular events during spinal fusion process. The gene expression profile suggests that control release of bone morphogenetic protein-2 (BMP-2) resulted in lower inflammatory and osteoclastic activities, but elicited higher osteogenic activities, while burst release of BMP-2 resulted in predominantly inflammation and osteoclastogenesis with minimum osteogenic activity. This study provides the molecular evidence that underscores the regeneration outcomes from the two different BMP-2 delivery systems. This spinal fusion chamber could be used for future molecular studies to optimize carrier design for spinal fusion.

Immobilization of vitronectin-binding heparan sulfates onto surfaces to support human pluripotent stem cells.

Functionalizing medical devices with polypeptides to enhance their performance has become important for improved clinical success. The extracellular matrix (ECM) adhesion protein vitronectin (VN) is an effective coating, although the chemistry used to attach VN often reduces its bioactivity. In vivo, VN binds the ECM in a sequence-dependent manner with heparan sulfate (HS) glycosaminoglycans. We reasoned therefore that sequence-based affinity chromatography could be used to isolate a VN-binding HS fraction (HS9) for use as a coating material to capture VN onto implant surfaces. Binding avidity and specificity of HS9 were confirmed by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR)-based assays. Plasma polymerization of allylamine (AA) to tissue culture-treated polystyrene (TCPS) was then used to capture and present HS9 as determined by radiolabeling and ELISA. HS9-coated TCPS avidly bound VN, and this layered surface supported the robust attachment, expansion, and maintenance of human pluripotent stem cells. Compositional analysis demonstrated that 6-O- and N-sulfation, as well as lengths greater than three disaccharide units (dp6) are critical for VN binding to HS-coated surfaces. Importantly, HS9 coating reduced the threshold concentration of VN required to create an optimally bioactive surface for pluripotent stem cells. We conclude that affinity-purified heparan sugars are able to coat materials to efficiently bind adhesive factors for biomedical applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1887-1896, 2018.

Fabrication of polycaprolactone-silanated ß-tricalcium phosphate-heparan sulfate scaffolds for spinal fusion applications.

BACKGROUND CONTEXT: Interbody spinal fusion relies on the use of external fixation and the placement of a fusion cage filled with graft materials (scaffolds) without regard for their mechanical performance. Stability at the fusion site is instead reliant on fixation hardware combined with a selected cage. Ideally, scaffolds placed into the cage should both support the formation of new bone and contribute to the mechanical stability at the fusion site. PURPOSE: We recently developed a scaffold consisting of silane-modified PCL-TCP (PCL-siTCP) with mechanical properties that can withstand the higher loads generated in the spine. To ensure the scaffold more closely mimicked the bone matrix, we incorporated collagen (Col) and a heparan sulfate glycosaminoglycan sugar (HS3) with increased affinity for heparin-binding proteins such as bone morphogenetic protein-2 (BMP-2). The osteostimulatory characteristic of this novel device delivering exogenous BMP2 was assessed in vitro and in vivo as a prelude to future spinal fusion studies with this device. STUDY DESIGN/SETTING: A combination of cell-free assays (BMP2 release), progenitor cell-based assays (BMP2 bioactivity, cell proliferation and differentiation), and rodent ectopic bone formation assays was used to assess the osteostimulatory characteristics of the PCL-siTCP-based scaffolds. MATERIALS AND METHODS: Freshly prepared rat mesenchymal stem cells were used to determine reparative cell proliferation and differentiation on the PCL-siTCP-based scaffolds over a 28-day period in vitro. The bioactivity of BMP2 released from the scaffolds was assessed on progenitor cells over a 28-day period using ALP activity assays and release kinetics as determined by enzyme-linked immunosorbent assay. For ectopic bone formation, intramuscular placement of scaffolds into Sprague Dawley rats (female, 4 weeks old, 120-150 g) was achieved in five animals, each receiving four treatments randomized for location along the limb. The four groups tested were (1) PCL-siTCP/Col (5-mm diameter×1-mm thickness), PCL-siTCP/Col/BMP2 (5 µg), (3) PCL-siTCP/Col/HS3 (25 µg), and (4) PCL-siTCP/Col/HS3/BMP2 (25 and 5 µg, respectively). Bone formation was evaluated at 8 weeks post implantation by microcomputed tomography (µCT) and histology. RESULTS: Progenitor cell-based assays (proliferation, mRNA transcripts, and ALP activity) confirmed that BMP2 released from PCL-siTCP/Col/HS3 scaffolds increased ALP expression and mRNA levels of the osteogenic biomarkers Runx2, Col1a2, ALP, and bone gla protein-osteocalcin compared with devices without HS3. When the PCL-siTCP/Col/HS3/BMP2 scaffolds were implanted into rat hamstring muscle, increased bone formation (as determined by two-dimensional and three-dimensional µCTs and histologic analyses) was observed compared with scaffolds lacking BMP2. More consistent increases in the amount of ectopic bone were observed for the PCL-siTCP/Col/HS3/BMP2 implants compared with PCL-siTCP/Col/BMP2. Also, increased mineralizing tissue within the pores of the scaffold was seen with modified-tetrachrome histology, a result confirmed by µCT, and a modest but detectable increase in both the number and the thickness of ectopic bone structures were observed with the PCL-siTCP/Col/HS3/BMP2 implants. CONCLUSIONS: The combination of PCL-siTCP/Col/HS3/BMP2 thus represents a promising avenue for further development as a bone graft alternative for spinal fusion surgery.

Yolk shell nanocomposite particles as bioactive bone fillers and growth factor carriers.

The efficient delivery of bioactive molecules via rationally designed nanoparticles is an important focus in regenerative medicine. The yolk shell nanocomposite particles described herein are composed of silk fibroin movable cores formed within voided calcium carbonate shells to load and control the release of labile cytokines. These particles are excellent carrier vehicles of potent molecules as they sustained the release of bioactive Bone Morphogenetic Protein 2 (BMP-2) for more than 28 days in vitro. Implantation into bone defects in rabbits corroborates the in vitro results and also reveals that upon contact with phosphate containing body fluids, implanted yolk shell particles agglomerate and transform into a filler that adapts to defect contour to further act as an absorbable hemostatic agent. Taken together, the fabrication of these yolk shell particle-based "bone fillers" could expand the horizon for the development of newer generations of advanced bioactive materials in tissue regeneration applications.

Antagonist muscle co-contraction during a double-leg landing maneuver at two heights.

BACKGROUND: Knee injuries are common during landing activities. Greater landing height increases peak ground reaction forces (GRFs) and loading at the knee joint. As major muscles to stabilize the knee joint, Quadriceps and Hamstring muscles provide internal forces to attenuate the excessive GRF. Despite the number of investigations on the importance of muscle function during landing, the role of landing height on these muscles forces using modeling during landing is not fully investigated. METHODS: Participant-specific musculoskeletal models were developed using experimental motion analysis data consisting of anatomic joint motions and GRF from eight male participants performing double-leg drop landing from 30 and 60 cm. Muscle forces were calculated in OpenSim and their differences were analyzed at the instances of high risk during landing i.e. peak GRF for both heights. RESULTS: The maximum knee flexion angle and moments were found significantly higher from a double-leg landing at 60 cm compared to 30 cm. The results showed elevated GRF, and mean muscle forces during landing. At peak GRF, only quadriceps showed significantly greater forces at 60 cm. Hamstring muscle forces did not significantly change at 60 cm compared to 30 cm. CONCLUSIONS: Quadriceps and hamstring muscle forces changed at different heights. Since hamstring forces were similar in both landing heights, this could lead to an imbalance between the antagonist muscles, potentially placing the knee at risk of injury if combined with small flexion angles that was not observed at peak GRF in our study. Thus, enhanced neuromuscular training programs strengthening the hamstrings may be required to address this imbalance. These findings may contribute to enhance neuromuscular training programs to prevent knee injuries during landing.

Effective Light Directed Assembly of Building Blocks with Microscale Control.

Light-directed forces have been widely used to pattern micro/nanoscale objects with precise control, forming functional assemblies. However, a substantial laser intensity is required to generate sufficient optical gradient forces to move a small object in a certain direction, causing limited throughput for applications. A high-throughput light-directed assembly is demonstrated as a printing technology by introducing gold nanorods to induce thermal convection flows that move microparticles (diameter = 40 µm to several hundreds of micrometers) to specific light-guided locations, forming desired patterns. With the advantage of effective light-directed assembly, the microfluidic-fabricated monodispersed biocompatible microparticles are used as building blocks to construct a structured assembly (≈10 cm scale) in ≈2 min. The control with microscale precision is approached by changing the size of the laser light spot. After crosslinking assembly of building blocks, a novel soft material with wanted pattern is approached. To demonstrate its application, the mesenchymal stem-cell-seeded hydrogel microparticles are prepared as functional building blocks to construct scaffold-free tissues with desired structures. This light-directed fabrication method can be applied to integrate different building units, enabling the bottom-up formation of materials with precise control over their internal structure for bioprinting, tissue engineering, and advanced manufacturing.

A Magnetic Resonance Compatible Soft Wearable Robotic Glove for Hand Rehabilitation and Brain Imaging.

In this paper, we present the design, fabrication and evaluation of a soft wearable robotic glove, which can be used with functional Magnetic Resonance imaging (fMRI) during the hand rehabilitation and task specific training. The soft wearable robotic glove, called MR-Glove, consists of two major components: a) a set of soft pneumatic actuators and b) a glove. The soft pneumatic actuators, which are made of silicone elastomers, generate bending motion and actuate finger joints upon pressurization. The device is MR-compatible as it contains no ferromagnetic materials and operates pneumatically. Our results show that the device did not cause artifacts to fMRI images during hand rehabilitation and task-specific exercises. This study demonstrated the possibility of using fMRI and MR-compatible soft wearable robotic device to study brain activities and motor performances during hand rehabilitation, and to unravel the functional effects of rehabilitation robotics on brain stimulation.