Sodium thiosulfate: A donor or carrier signaling molecule for hydrogen sulfide?

Sodium thiosulfate has been used for decades in the treatment of calciphylaxis and cyanide detoxification, and has recently shown initial therapeutic promise in critical diseases such as neuronal ischemia, diabetes mellitus, heart failure and acute lung injury. However, the precise mechanism of sodium thiosulfate remains incompletely defined and sometimes contradictory. Although sodium thiosulfate has been widely accepted as a donor of hydrogen sulfide (H2S), emerging findings suggest that it is the executive signaling molecule for H2S and that its effects may not be dependent on H2S. This article presents an overview of the current understanding of sodium thiosulfate, including its synthesis, biological characteristics, and clinical applications of sodium thiosulfate, as well as the underlying mechanisms in vivo. We also discussed the interplay of sodium thiosulfate and H2S. Our review highlights sodium thiosulfate as a key player in sulfide signaling with the broad clinical potential for the future.

"Win-Win" Modification of LiCoO2 Enables Stable and Long-Life Cycling of Sulfide-Based All Solid-State Batteries.

Interfacial side reactions and space charge layers between the oxide cathode material and the sulfide solid-state electrolytes (SSEs), along with the structural degradation of the active material, significantly compromise the electrochemical performance of all-solid-state batteries (ASSLBs). Surface coating and bulk doping of the cathodes are considered the most effective approaches to mitigate the interface issues between the cathode and SSEs and enhance the structural integrity of composite cathodes. Here, a one-step low-cost means is ingeniously designed to modify LiCoO2 (LCO) with heterogeneous Li2 TiO3 /Li(TiMg)1/2 O2 surface coating and bulk gradient Mg doping. When applied in Li10 GeP2 S12 -based ASSLBs, the Li2 TiO3 and Li(TiMg)1/2 O2 coating layers effectively suppress interfacial side reactions and weaken space charge layer effect. Furthermore, gradient Mg doping stabilizes the bulk structure to mitigate the formation of spinel-like phases during local overcharging caused by solid-solid contact. The modified LCO cathodes exhibit excellent cycle performance with a capacity retention of 80 % after 870 cycles. This dual-functional strategy provides the possibility for large-scale commercial implementation of cathodes modification in sulfide based ASSLBs in the future.

Probing the degradation of LiCoO2 in batteries subjected to high-voltage cycling with 17O solid-state NMR spectroscopy.

The long-term cycling stability of LiCoO2 under high-voltage operation in lithium-ion batteries is still not satisfactory and the mechanism of capacity decay is not well understood. Here we mainly apply 17O MAS NMR spectroscopy to probe the phase transformation of cycled LiCoO2 cathodes in both liquid cells and solid cells. It turns out that deterioration into the spinel phase is the main cause.

All-Solid-State Batteries with Pre-plated Ultrathin Lithium Metal Enabled by No Pressure Holding and Characterized by In Situ Electron Paramagnetic Resonance Imaging.

All-solid-state batteries with ultrathin lithium metal, close to the anode-free solid-state batteries, could achieve high energy density. However, it is not trivial to plate an ultrathin lithium metal layer on a Cu current collector (Cu-CC). In situ electron paramagnetic resonance (EPR) imaging showed that the pre-plating on Cu-CC in a Li-In|Li6PS5Cl|Cu cell without pressure holding produced a lithium metal layer with a small area. However, when a Li-In|Li6PS5Cl|Cu cell was held under a considerable pressure, this cell would produce a lithium metal layer with a large area. The Cu-CC with the ultrathin lithium metal layer of a small surface could be extracted and then assembled with LiNiO2 and Li6PS5Cl to achieve better electrochemical performance compared to that of a large surface, because a small area of the lithium metal layer would lead to fewer side reactions and less consumption of lithium ions. This work suggests the importance of the control of the lithium plating and the observation of lithium plating by in situ EPR imaging.

Measuring T1 relaxation in paramagnetic solids with solid-state NMR: a case study on the milling induced phase transition in Li6CoO4.

Solid-state NMR has been a vital tool for the study of structural evolution of cathodes in lithium-ion and sodium-ion batteries. However, the differentiation of relaxation parameters for certain sites is difficult owing to limited spectral resolution associated with strong anisotropic hyperfine interaction. Here we propose a novel IR-pjMATPASS method that can measure T1 relaxation with site-specific resolution for paramagnetic solids. We apply this method to the characterization of ball-milling induced order-disorder phase transition in Li6CoO4 as a case study. The quasi-quantitate 7Li NMR enables the synthetic optimization of high energy ball-milling conditions to harvest a disordered cubic phase through site-specific 7Li T1 measurements. The example study shown here provides a quantitative strategy for NMR studies of paramagnetic solids.

Characterizing the inherent activity of urinary bladder matrix for adhesion, migration, and activation of fibroblasts as compared with collagen-based synthetic scaffold.

The mechanism of action underlying the intriguing prominent bioactivity of urinary bladder matrix (UBM) for in situ tissue regeneration of soft tissue defects remains to be elucidated. It is speculated that the activity of UBM for cell adhesion, migration, and activation is inherent. The bioactivity of UBM for in situ tissue regeneration and its relation with the structure and intact soluble components of UBM were investigated in comparison to a collagen-based scaffold, PELNAC (PEL). We isolated the soluble component of the two materials with urea buffer, and evaluated the respective effect of these soluble components on the in vitro adhesion and migration of L929 fibroblasts. The spatiotemporal pattern of endogenous-cell ingrowth into the scaffolds and cell activation were investigated using a model of murine subcutaneous implantation. UBM is more capable of promoting the adhesion, migration, and proliferation of fibroblasts than PEL in a serum-independent manner. In vivo, as compared with PEL, UBM exhibits significantly enhanced activity for fast endogenous cell ingrowth and produces a more prominent pro-regenerative and pro-remodeling microenvironment by inducing the expression of TGF-ß1, VEGF, MMP-9, and murine type I collagen. Overall, our results suggest the prominent bioactivity of UBM for in situ tissue regeneration is inherent.

Quantitative and space-resolved in situ 1D EPR imaging for the detection of metallic lithium deposits.

The ability to monitor lithium deposition on the anodes in real time is becoming progressively more important due to the development of advanced anode technology. Given the fact that the detrimental Li deposits are always on the micron scale, electron paramagnetic resonance (EPR) happens to be a very effective and selective detection technology due to the skin effect. Here, quantitative in situ 1D EPR imaging is carried out with a magnetic field gradient to achieve a one-dimensional spatial resolution along the Li growth direction in a capillary cell. The quantification of Li deposits is carefully calibrated using a 1,1-diphenyl-2-picrylhydrazyl standard, and a processing method is presented to correct the double integration of the Dysonian line from the metallic Li. The Li deposition processes are compared in two different electrolytes. For the electrolyte containing fluoroethylene carbonate (FEC) additive, the fitting results of Dysonian lines suggest that the plated Li has a larger dimension of the microstructure and the stripping proceeds more uniformly. It thus accounts for the higher Coulombic efficiency in the electrolyte with FEC. In situ EPR imaging also suggests that the Sand's capacity varies with the electrolytes. The forced growth of dendritic Li is carried out at a very large current density using a derivative operando EPR method to monitor the growth locus of the Li dendrites, indicating a tip-growing mechanism. This work can be instructive for those who are engaged in the study of electro-deposited lithium using in situ EPR imaging technology.

Mesenchymal stem cells pretreated with proinflammatory cytokines accelerate skin wound healing by promoting macrophages migration and M2 polarization.

Introduction: Numerous studies have shown that mesenchymal stem cells (MSCs) promote cutaneous wound healing via paracrine signaling. Our previous study found that the secretome of MSCs was significantly amplified by treatment with IFN-γ and TNF-α (IT). It has been known that macrophages are involved in the initiation and termination of inflammation, secretion of growth factors, phagocytosis, cell proliferation and collagen deposition in wound, which is the key factor during wound healing. In the present study, we used a unique supernatant of MSCs from human umbilical cord-derived MSCs (UC-MSCs) pretreated with IT, designated S-IT MSCs, to explore whether S-IT MSCs have a better effect on improving wound healing by improving the biological function of macrophages than the control supernatant of MSCs (S-MSCs). Methods: In the present study, we used a unique supernatant of MSCs pretreated with IT subcutaneously injected into a mice total skin excision. We evaluated the effect of S-IT MSCs on wound healing and the quality of wound repair via promoting macrophages migration and M2 polarization in vivo. In addition, the effect of S-IT MSCs on macrophages migration, converting toward M2 phenotype and phagocytosis were also investigated in vitro. Results: Indeed, S-IT MSCs were found to be more potent in promoting macrophage migration, M2 polarization, phagocytosis, and promoting wound closure than S-MSCs during the wound repair. High levels of CCL2 and IL-6 were found in S-IT MSCs, which indicated that the optimization of macrophage function by S-IT MSCs may be achieved through their high expression of CCL2 and IL-6. Conclusions: Our results suggest that the beneficial paracrine effect of MSCs on wound healing can be amplified by pretreatment with IT, which may represent a new strategy for optimizing the therapeutic effect of MSCs on wound healing.

Mesenchymal stromal cells pretreated with proinflammatory cytokines enhance skin wound healing via IL-6-dependent M2 polarization.

BACKGROUND: Numerous studies have shown that mesenchymal stromal cells (MSCs) promote cutaneous wound healing via paracrine signaling. Our previous study found that the secretome of MSCs was significantly amplified by treatment with IFN-γ and TNF-α (IT). It has been known that macrophages are involved in the initiation and termination of inflammation, secretion of growth factors, phagocytosis, cell proliferation, and collagen deposition in wound, which is the key factor during wound healing. In this study, we aim to test whether the supernatant of MSCs pretreated with IT (S-IT MSCs) possesses a more pronounced effect on improving wound healing and describe the interplay between S-IT MSCs and macrophages as well as the potential mechanism in skin wound healing. METHODS: In the present study, we used a unique supernatant of MSCs from human umbilical cord-derived MSCs (UC-MSCs) pretreated with IT, designated S-IT MSCs, subcutaneously injected into a mice total skin excision. We evaluated the effect of S-IT MSCs on the speed and quality of wound repair via IT MSCs-derived IL-6-dependent M2 polarization in vivo by hematoxylin-eosin staining (H&E), immunohistochemistry (IHC), immunofluorescence (IF), Masson's trichrome staining, Sirius red staining, quantitative real-time PCR (qPCR). In addition, the effect of S-IT MSCs on the polarization of macrophages toward M2 phenotype and the potential mechanism of it were also investigated in vitro by flow cytometry (FCM), enzyme-linked immunosorbent assay (ELISA), tube formation assay, and western blot analysis. RESULTS: Compared with control supernatant (S-MSCs), our H&E and IF results showed that S-IT MSCs were more effectively in promoting macrophages convert to the M2 phenotype and enhancing phagocytosis of M2 macrophages. Meanwhile, the results of tube formation assay, IHC, Masson's trichrome staining, Sirius red staining showed that the abilities of M2 phenotype to promote vascularization and collagen deposition were significantly enhanced by S-IT MSCs-treated, thereby accelerating higher quality wound healing. Further, our ELISA, FCM, qPCR and western blot results showed that IL-6 was highly enriched in S-IT MSCs and acted as a key regulator to induce macrophages convert to the M2 phenotype through IL-6-dependent signaling pathways, ultimately achieving the above function of promoting wound repair. CONCLUSIONS: These findings provide the first evidence that the S-IT MSCs is more capable of eliciting M2 polarization of macrophages via IL-6-dependent signaling pathways and accelerating wound healing, which may represent a new strategy for optimizing the therapeutic effect of MSCs on wound healing.

Distinguishing the Effects of the Space-Charge Layer and Interfacial Side Reactions on Li10GeP2S12-Based All-Solid-State Batteries with Stoichiometric-Controlled LiCoO2.

All-solid-state lithium batteries (ASSLBs) with high volumetric energy density and enhanced safety are considered one of the most promising next-generation batteries. Elucidating the capacity-fading mechanism caused by the space-charge layer (SCL) and the interfacial side reaction (ISR) is crucial for the future development of high-energy-density ASSLBs with a longer cycle life. Here, a systematic study to probe the electrochemical performance of Li10GeP2S12-based ASSLBs with stoichiometric-controlled LixCoO2 was performed with the aid of density functional theory (DFT) calculations, X-ray photoelectron spectroscopy (XPS), focused ion beam-field emission scanning electron microscopy (FIB-SEM), and solid-state nuclear magnetic resonance (NMR) spectroscopy. We discovered that the overstoichiometric Li1.042CoO2 shows a high capacity at first cycle with the smallest overpotential, but the capacity gradually decreases, which is ascribed to the weak SCL effect and strong interfacial side reactions. On the contrary, the lithium-deficient Li0.945CoO2 achieves the best cycling stability with a very low capacity associated with the strongest SCL effect and weak interfacial side reactions. The SCL effect is indeed coupled with ISR, which eventually leads to capacity fading in long-term operation. We believe that the new insights gained from this work will accelerate the future development of LiCoO2/LGPS-based ASSLBs with both a mitigated SCL effect and a longer cycle life.

The conditioned medium from mesenchymal stromal cells pretreated with proinflammatory cytokines promote fibroblasts migration and activation.

Human dermal fibroblasts (HDFs) play important roles in all stages of wound healing. However, in nonhealing wounds, fibroblasts are prone to aging, resulting in insufficient migration, proliferation and secretion functions. Recent studies have suggested that mesenchymal stromal cells (MSCs) are conducive to wound healing and cell growth through paracrine cytokine signaling. In our studies, we found that conditioned medium of MSCs pretreated with IFN-γ and TNF-α (IT MSC-CM) has abundant growth factors associated with wound repair. Our in vitro results showed that the effects of IT MSC-CM on promoting cell migration, proliferation and activation in HDFs were better than those of conditioned medium from mesenchymal stromal cells (MSC-CM). Moreover, we embedded a scaffold material containing IT MSC-CM and reconfirmed that cell migration and activation were superior to that in the presence of MSC-CM in vivo. Generally, PDGF-BB is perceived as a promoter of the migration and proliferation of HDFs. Moreover, a high level of PDGF-BB in IT MSC-CM was detected, according to which we guess that the effect on HDFs may be mediated by the upregulation of PDGF-BB. These studies all showed the potential of IT MSC-CM to promote rapid and effective wound healing.

Injectable silk nanofiber hydrogels as stem cell carriers to accelerate wound healing.

Stem cells have potential utility in wound therapy, however the benefits are often limited due to cell injury from shear stress during injection and poor retention at the wound site. Here, shear-thinning silk nanofiber hydrogels were used to load bone marrow derived mesenchymal stem cells (BMSCs) and inject into wound sites to optimize cell retention and accelerate wound healing. The BMSCs in the silk nanofiber hydrogels maintained stemness better than the cells cultured on plates, and the expression of wound healing-related genes was significantly higher in the hydrogels with higher silk concentrations (2 wt%). The silk nanofibers physically prevented migration of BMSCs from the deposition site in the wound bed. In addition to faster wound healing, these BMSC-loaded hydrogels mediated angiogenesis and inflammation and improved collagen deposition and hair follicle regeneration in vivo in rats. Considering that these silk nanofiber hydrogels were successfully used here as carriers for stem cells to accelerate wound healing, further study for skin regeneration may be warranted.

Injectable Desferrioxamine-Laden Silk Nanofiber Hydrogels for Accelerating Diabetic Wound Healing.

Dysangiogenesis and chronic inflammation are two critical reasons for diabetic foot ulcers. Desferrioxamine (DFO) was used clinically in the treatment of diabetic foot ulcers by repeated injections because of its capacity to induce vascularization. Biocompatible carriers that release DFO slowly and facilitate healing simultaneously are preferable options to accelerate the healing of diabetic wounds. Here, DFO-laden silk nanofiber hydrogels that provided a sustained release of DFO for more than 40 days were used to treat diabetic wounds. The DFO-laden hydrogels stimulated the healing of diabetic wounds. In vitro cell studies revealed that the DFO-laden hydrogels modulated the migration and gene expression of endothelial cells, and they also tuned the inflammation behavior of macrophages. These results were confirmed in an in vivo diabetic wound model. The DFO-laden hydrogels alleviated dysangiogenesis and chronic inflammation in the diabetic wounds, resulting in a more rapid wound healing and increased collagen deposition. Both in vitro and in vivo studies suggested potential clinical applications of these DFO-laden hydrogels in the treatment of diabetic ulcers.

Clinical features and mortality-related factors of extensive burns among young adults: the Kunshan disaster experience.

BACKGROUND: The aim of the study was to identify the clinical features and the factors associated with burn induced mortality among young adults after exposure to indoor explosion and fire. METHODS: This is an observational study which included burn patients who were admitted to eighteen ICUs after a fire disaster. Epidemiologic and clinical characteristics, as well as therapy were recorded. The primary outcome was 90-day mortality. The mortality-related factors were also analyzed. RESULTS: There were 167 burn patients enrolled in the study, the median age was 38 years, 62 (37.1%) patients died within 90 days. Seventy-one percent of patients had a burn size ≥90% TBSA, and 73.7% of patients had a full-thickness burn area above 50% TBSA. The survivors had lower Baux scores, and received earlier escharectomy and autologous skin grafts. The 50% mortality rates (LA50s) for burn size and full-thickness burn area were 95.8% and 88.6% TBSA, respectively. The multivariate analysis showed that full-thickness burn area over 50% TBSA and residual burned surface area (RBSA)/TBSA at 28 days were strong predictors of mortality among burn patients (odds ratio 2.55; 95% CI, 1.01 to 6.44, P=0.047; odds ratio 1.07; 95% CI, 1.04 to 1.09, P<0.001). The ROC curve-based cut-off values of RBSA/TBSA at 28 days for predicting 90-day mortality were 62.5%. CONCLUSIONS: Burn size and full-thickness burn area were the main risk factors for poor outcome in patients with extensive burns. Earlier escharectomy and autologous skin grafts may improve outcomes.

Microskin-Inspired Injectable MSC-Laden Hydrogels for Scarless Wound Healing with Hair Follicles.

Scarless skin regeneration with functional tissue remains a challenge for full-thickness wounds. Here, mesenchymal stem cell (MSC)-laden hydrogels are developed for scarless wound healing with hair follicles. Microgels composed of aligned silk nanofibers are used to load MSCs to modulate the paracrine. MSC-laden microgels are dispersed into injectable silk nanofiber hydrogels, forming composites biomaterials containing the cells. The injectable hydrogels protect and stabilize the MSCs in the wounds. The synergistic action of silk-based composite hydrogels and MSCs stimulated angiogenesis and M1-M2 phenotype switching of macrophages, provides a suitable niche for functional recovery of wounds. Compared to skin defects treated with MSC-free hydrogels, the defects treated with the MSC-laden composite hydrogels heal faster and form scarless tissues with hair follicles. Wound healing can be further improved by adjusting the ratio of silk nanofibers and particles and the loaded MSCs, suggesting tunability of the system. To the best of current knowledge, this is the first time scarless skin regeneration with hair follicles based on silk material systems is reported. The improved wound healing capacity of the systems suggests future in vivo studies to compare to other biomaterial systems related to clinical goals in skin regeneration in the absence of scarring.

Injectable hydrogel systems with multiple biophysical and biochemical cues for bone regeneration.

Bone regeneration is a complex process in which angiogenesis and osteogenesis are crucial. Introducing multiple angiogenic and osteogenic cues simultaneously into a single system and tuning these cues to optimize the niche remains a challenge for bone tissue engineering. Herein, based on our injectable biomimetic hydrogels composed of silk nanofibers (SNF) and hydroxyapatite nanoparticles (HA), deferoxamine (DFO) and bone morphogenetic protein-2 (BMP-2) were loaded on SNF and HA to introduce more angiogenic and osteogenic cues. The angiogenesis and osteogenesis capacity of injectable hydrogels could be regulated by tuning the delivery of DFO and BMP-2 independently, resulting in vascularization and bone regeneration in cranial defects. The angiogenesis and osteogenesis outcomes accelerated the regeneration of vascularized bones toward similar composition and structure to natural bones. Therefore, the multiple biophysical and chemical cues provided by the nanofibrous structures, organic-inorganic compositions, and chemical and biochemical angiogenic and osteogenic inducing cues suggest the potential for clinical applicability of these hydrogels in bone tissue engineering.

Electric field-driven building blocks for introducing multiple gradients to hydrogels.

Gradient biomaterials are considered as preferable matrices for tissue engineering due to better simulation of native tissues. The introduction of gradient cues usually needs special equipment and complex process but is only effective to limited biomaterials. Incorporation of multiple gradients in the hydrogels remains challenges. Here, beta-sheet rich silk nanofibers (BSNF) were used as building blocks to introduce multiple gradients into different hydrogel systems through the joint action of crosslinking and electric field. The blocks migrated to the anode along the electric field and gradually stagnated due to the solution-hydrogel transition of the systems, finally achieving gradient distribution of the blocks in the formed hydrogels. The gradient distribution of the blocks could be tuned easily through changing different factors such as solution viscosity, which resulted in highly tunable gradient of mechanical cues. The blocks were also aligned under the electric field, endowing orientation gradient simultaneously. Different cargos could be loaded on the blocks and form gradient cues through the same crosslinking-electric field strategy. The building blocks could be introduced to various hydrogels such as Gelatin and NIPAM, indicating the universality. Complex niches with multiple gradient cues could be achieved through the strategy. Silk-based hydrogels with suitable mechanical gradients were fabricated to control the osteogenesis and chondrogenesis. Chondrogenic-osteogenic gradient transition was obtained, which stimulated the ectopic osteochondral tissue regeneration in vivo. The versatility and highly controllability of the strategy as well as multifunction of the building blocks reveal the applicability in complex tissue engineering and various interfacial tissues.

Natural Nanofiber Shuttles for Transporting Hydrophobic Cargo into Aqueous Solutions.

Hydrophobic biomolecules realize their functions in vivo in aqueous environments, often through a delicate balance of amphiphilicity and chaperones. Introducing exogenous hydrophobic biomolecules into in vivo aqueous systems is a challenge in drug delivery and regenerative medicine, where labile linkers, carriers, and fusions or chimeric molecules are often designed to facilitate such aqueous interfaces. Here, we utilize naturally derived silk nanofiber shuttles with the capacity to transport hydrophobic cargos directly into aqueous solutions. These nanofibers disperse in organic solvents and in aqueous solutions because of their inherent amphiphilicity, with enriched hydrophobicity and strategically interspersed negatively charged groups. Hydrophobic molecules loaded on these shuttles in organic solvent-water systems separated from the solvent after centrifugation. These concentrated hydrophobic molecule-loaded nanofibers could then be dispersed into aqueous solution directly without modification. These shuttle systems were effective for different hydrophobic molecules such as drugs, vitamins, and dyes. Improved biological stability and functions of hydrophobic cargos after loading on these nanofibers suggest potential applications in drug delivery, cosmetology, medical diagnosis, and related health fields, with a relatively facile process.

Microfluidic Silk Fibers with Aligned Hierarchical Microstructures.

The hierarchical structure of the ECM provides specific niches for tissues to regulate cell behavior, yet the challenge remains to design biomaterial systems for tissue regeneration to recreate such features in vitro. Here, we achieved this goal through the use of aligned hierarchical structures of native silk fibers, generated through the integration of "bottom-up" and "top-down" strategies to generate regenerated silk fibers with aligned nano- to micro-hierarchical structures. To achieve these designs, we assembled and dispersed silk nanofibers (SNF) in formic acid and spun them into fibers using bioinspired microfluidic chips with a geometry mimicking the native silk gland. The fibers generated using this device exhibited aligned hierarchical structure with fiber mechanical properties superior to fibers derived from more traditional spinning approaches with regenerated silk solutions. Besides the improved mechanical properties, Raman spectroscopic results indicated similarly aligned structures to native fibers and active control of cell proliferation, migration, and aggregate orientation. The results indicate the feasibility of developing bioactive silk fiber materials with hierarchical structures to facilitate utility in a range of cell and tissue regeneration scenarios.

Tough Anisotropic Silk Nanofiber Hydrogels with Osteoinductive Capacity.

Multiple physical cues such as hierarchical microstructures, topography, and stiffness influence cell fate during tissue regeneration. Yet, introducing multiple physical cues to the same biomaterial remains a challenge. Here, a synergistic cross-linking strategy was developed to fabricate protein hydrogels with multiple physical cues based on combinations of two types of silk nanofibers. ß-sheet-rich silk nanofibers (BSNFs) were blended with amorphous silk nanofibers (ASNFs) to form composite nanofiber systems. The composites were transformed into tough hydrogels through horseradish peroxidase (HRP) cross-linking in an electric field, where ASNFs were cross-linked with HRP, while BSNFs were aligned by the electrical field. Anisotropic morphologies and higher stiffness of 120 kPa were achieved. These anisotropic hydrogels induced osteogenic differentiation and the aligned aggregation of stem cells in vitro while also exhibiting osteoinductive capacity in vivo. Improved tissue outcomes with the hydrogels suggest promising applications in bone tissue engineering, as the processing strategy described here provides options to form hydrogels with multiple physical cues.