Electrospun Photocrosslinkable Hydrogel Fibrous Scaffolds for Rapid In Vivo Vascularized Skin Flap Regeneration

Distal necrosis of random skin flap is always clinical problematic in plastic surgery. The development of 3D functional vascular networks is fundamental for the survival of a local random skin flap. Herein, an effective technique on constructing 3D fibrous scaffolds for accelerated vascularization is demonstrated using a photocrosslinkable natural hydrogel based on gelatin methacryloyl (GelMA) by electrospinning. It is found that the ultraviolet (UV) photocrosslinkable gelatin electrospun hydrogel fibrous membranes exhibit soft adjustable mechanical properties and controllable degradation properties. Furthermore, it is observed that the optimized hydrogel scaffolds can support endothelial cells and dermal fibroblasts adhesion, proliferation, and migration into the scaffolds, which facilitates vascularization. Importantly, a rapid formation of tubes is observed after 3 d seeding of endothelial cells. After GelMA fibrous scaffold implantation below the skin flap in a rat model, it is found that the flap survival rate is higher than the control group, and there is more microvascular formation, which is potentially beneficial for the flap tissue vascularization. These data suggest that GelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.     

Black‐Phosphorus‐Incorporated Hydrogel as a Conductive and Biodegradable Platform for Enhancement of the Neural Differentiation of Mesenchymal Stem Cells

Conductive hydrogel scaffolds have important applications for electroactive tissue repairs. However, the development of conductive hydrogel scaffolds tends to incorporate nonbiodegradable conductive nanomaterials that will remain in the human body as foreign matters. Herein, a biodegradable conductive hybrid hydrogel is demonstrated based on the integration of black phosphorus (BP) nanosheets into the hydrogel matrix. To address the challenge of applying BP nanosheets in tissue engineering due to its intrinsic instability, a polydopamine (PDA) modification method is developed to improve the stability. Moreover, PDA modification also enhances interfacial bonding between pristine BP nanosheets and the hydrogel matrix. The incorporation of polydopamine‐modified black phosphorous (BP@PDA) nanosheets into the gelatin methacryloyl (GelMA) hydrogels significantly enhances the electrical conductivity of the hydrogels and improves the cell migration of mesenchymal stem cells (MSCs) within the 3D scaffolds. On the basis of the gene expression and protein level assessments, the BP@PDA‐incorporated GelMA scaffold can significantly promote the differentiation of MSCs into neural‐like cells under the synergistic electrical stimulation. This strategy of integrating biodegradable conductive BP nanomaterials within a biocompatible hydrogel provides a new insight into the design of biomaterials for broad applications in tissue engineering of electroactive tissues, such as neural, cardiac, and skeletal muscle tissues.     

Induction of Four-Dimensional Spatiotemporal Geometric Transformations in High Cell Density Tissues via Shape-Changing Hydrogels

Developing and healing tissues begin as cellular condensations. Spatiotemporal changes in tissue geometry, transformations in the spatial distribution of the cells, and extracellular matrix are essential for its evolution into a functional tissue. 4D materials, 3D materials capable of geometric changes, may have the potential to recreate the aforementioned biological phenomenon. However, most reported 4D materials are non-degradable and/or not biocompatible, limiting their application in regenerative medicine, and to date, there are no systems controlling the geometry of high density cellular condensations and differentiation. Here, 4D high cell density tissues based on shape-changing hydrogels are described. By sequential photocrosslinking of oxidized and methacrylated alginate (OMA) and methacrylated gelatin (GelMA), bilayered hydrogels presenting controllable geometric changes without any external stimuli are fabricated. Fibroblasts and human adipose-derived stem cells (ASCs) are encapsulated at concentrations up to 1.0 × 10⁸ cells mL^–1 in the 4D constructs, and controllable shape changes are achieved in concert with ASCs differentiated down chondrogenic and osteogenic lineages. Bioprinting of the high density cell-laden OMA and GelMA permits the formation of more complex constructs with defined 4D geometric changes, which may further expand the promise of this approach in regenerative medicine applications.     

In Situ Crosslinkable Gelatin Hydrogels for Vasculogenic Induction and Delivery of Mesenchymal Stem Cells

Clinical trials utilizing mesenchymal stem cells (MSCs) for severe vascular diseases have highlighted the need to effectively engraft cells and promote pro‐angiogenic activity. A functional material accomplishing these two goals is an ideal solution as spatiotemporal and batch‐to‐batch variability in classical therapeutic delivery can be minimized, and tissue regeneration would begin rapidly at the implantation site. Gelatin may serve as a promising biomaterial due to its excellent biocompatibility, biodegradability, and non‐immuno/antigenicity. However, the dissolution of gelatin at body temperature and quick enzymatic degradation in vivo have limited its use thus far. To overcome these challenges, an injectable, in situ crosslinkable gelatin was developed by conjugating enzymatically crosslinkable hydroxyphenyl propionic acid (GHPA). When MSCs are cultured in 3D in vitro or injected in vivo in GHPA, spontaneous endothelial differentiation occurs, as evidenced by marked increases in endothlelial cell marker expressions (Flk1, Tie2, ANGPT1, vWF) in addition to forming an extensive perfusable vascular network after 2‐week subcutaneous implantation. Additionally, favorable host macrophage response is achieved with GHPA as shown by decreased iNOS and increased MRC1 expression. These results indicate GHPA as a promising soluble factor‐free cell delivery template which induces endothelial differentiation of MSCs with robust neovasculature formation and favorable host response.     

Bioinspired Hydrogel Electrospun Fibers for Spinal Cord Regeneration

Fully simulating the components and microstructures of soft tissue is a challenge for its functional regeneration. A new aligned hydrogel microfiber scaffold for spinal cord regeneration is constructed with photocrosslinked gelatin methacryloyl (GelMA) and electrospinning technology. The directional porous hydrogel fibrous scaffold consistent with nerve axons is vital to guide cell migration and axon extension. The GelMA hydrogel electrospun fibers soak up water more than six times their weight, with a lower Young's modulus, providing a favorable survival and metabolic environment for neuronal cells. GelMA fibers further demonstrate higher antinestin, anti‐Tuj‐1, antisynaptophysin, and anti‐CD31 gene expression in neural stem cells, neuronal cells, synapses, and vascular endothelial cells, respectively. In contrast, anti‐GFAP and anti‐CS56 labeled astrocytes and glial scars of GelMA fibers are shown to be present in a lesser extent compared with gelatin fibers. The soft bionic scaffold constructed with electrospun GelMA hydrogel fibers not only facilitates the migration of neural stem cells and induces their differentiation into neuronal cells, but also inhibits the glial scar formation and promotes angiogenesis. Moreover, the scaffold with a high degree of elasticity can resist deformation without the protection of a bony spinal canal. The bioinspired aligned hydrogel microfiber proves to be efficient and versatile in triggering functional regeneration of the spinal cord.     

Micropatterning Alginate Substrates for In Vitro Cardiovascular Muscle on a Chip

Soft hydrogels such as alginate are ideal substrates for building muscle in vitro because they have structural and mechanical properties close to the in vivo extracellular matrix (ECM) network. However, hydrogels are generally not amenable to protein adhesion and patterning. Moreover, muscle structures and their underlying ECM are highly anisotropic, and it is imperative that in vitro models recapitulate the structural anisotropy in reconstructed tissues for in vivo relevance due to the tight coupling between sturcture and function in these systems. Two techniques to create chemical and structural heterogeneities within soft alginate substrates are presented and employed to engineer anisotropic muscle monolayers: i) microcontact printing lines of extracellular matrix proteins on flat alginate substrates to guide cellular processes with chemical cues and ii) micromolding of alginate surface into grooves and ridges to guide cellular processes with topographical cues. Neonatal rat ventricular myocytes as well as human umbilical artery vascular smooth muscle cells successfully attach to both these micropatterned substrates leading to subsequent formation of anisotropic striated and smooth muscle tissues. Muscular thin film cantilevers cut from these constructs are then employed for functional characterization of engineered muscular tissues. Thus, micropatterned alginate is an ideal substrate for in vitro models of muscle tissue because it facilitates recapitulation of the anisotropic architecture of muscle, mimics the mechanical properties of the ECM microenvironment, and is amenable to evaluation of functional contractile properties.     

Injectable Stem Cell‐Laden Photocrosslinkable Microspheres Fabricated Using Microfluidics for Rapid Generation of Osteogenic Tissue Constructs

Direct injection is a minimally invasive method of stem cell transplantation for numerous injuries and diseases. However, despite its promising potential, its clinical translation is difficult due to the low cell retention and engraftment after injection. With high versatility, high‐resolution control and injectability, microfabrication of stem‐cell laden biomedical hydrogels holds great potential as minimally invasive technology. Herein, a strategy of microfluidics‐assisted technology entrapping bone marrow‐derived mesenchymal stem cells (BMSCs) and growth factors in photocrosslinkable gelatin (GelMA) microspheres to ultimately generate injectable osteogenic tissue constructs is presented. Additionally, it is demonstrated that the GelMA microspheres can sustain stem cell viability, support cell spreading inside the microspheres and migration from the interior to the surface as well as enhance cell proliferation. This finding shows that encapsulated cells have the potential to directly and actively participate in the regeneration process. Furthermore, it is found that BMSCs encapsulated in GelMA microspheres show enhanced osteogenesis in vitro and in vivo, associated with a significant increase in mineralization. In short, the proposed strategy can be utilized to facilitate bone regeneration with minimum invasiveness, and can potentially be applied along with other matrices for extended applications.     

Programmed Shape‐Morphing Scaffolds Enabling Facile 3D Endothelialization

Rapid formation of a confluent endothelial monolayer is the key to the success of small‐diameter vascular grafts, which is significantly important for treating dangerous and even sometimes deadly vascular disorders. However, the difficulty to homogenously locate endothelial cells onto the lumen of small‐diameter tubular scaffolds makes 3D endothelialization greatly challenging. Here, novel shape‐morphing scaffolds enabling programmed deformation from planar shapes to small‐diameter tubular shapes are designed and developed by combining biocompatible shape memory polymer and electrospun nanofibrous membrane. Endothelial cells can be conveniently seeded and attached on the 2D surface of the scaffolds and subsequently self‐rolled into 3D organization at physiological temperature. Endothelial cell responses and functions are varied on the shape‐morphing scaffolds with different nanofibrous electrospun membranes as the inner layer, arisen from the inducement of scaffolds with different morphological, physical, and biochemical characteristics. Owing to excellent properties of the nanofibrous membrane fabricated by the coelectrospinning of poly‐ε‐caprolactone (PCL) and gelatin methacrylate (GelMA), the shape‐morphing scaffolds with a nanofibrous PCL/GelMA inner layer support desirable homogeneous endothelial cell attachment as well as the rapid formation of biomimetic cell–scaffold interaction and cell–cell interaction under the 3D cell culture condition, therefore offering a visible approach for facile 3D endothelialization.     

An Organoid for Woven Bone

Bone formation (osteogenesis) is a complex process in which cellular differentiation and the generation of a mineralized organic matrix are synchronized to produce a hybrid hierarchical architecture. To study the mechanisms of osteogenesis in health and disease, there is a great need for functional model systems that capture in parallel, both cellular and matrix formation processes. Stem cell-based organoids are promising as functional, self-organizing 3D in vitro models for studying the physiology and pathology of various tissues. However, for human bone, no such functional model system is yet available. This study reports the in vitro differentiation of human bone marrow stromal cells into a functional 3D self-organizing co-culture of osteoblasts and osteocytes, creating an organoid for early stage bone (woven bone) formation. It demonstrates the formation of an organoid where osteocytes are embedded within the collagen matrix that is produced by the osteoblasts and mineralized under biological control. Alike in in vivo osteocytes, the embedded osteocytes show network formation and communication via expression of sclerostin. The current system forms the most complete 3D living in vitro model system to investigate osteogenesis, both in physiological and pathological situations, as well as under the influence of external triggers (mechanical stimulation, drug administration).     

High‐Throughput Scaffold System for Studying the Effect of Local Geometry and Topology on the Development and Orientation of Sprouting Blood Vessels

Live tissues require vascular networks for cell nourishing. Mimicking the complex structure of native vascular networks in vitro requires understanding the governing factors of early tubulogenesis. Current vascularization protocols allow for spontaneous formation of vascular networks; however, there is still a need to provide control over the defined network structure. Moreover, there is little understanding on sprouting decision and migration, especially within 3D environments. Here, tessellated polymer scaffolds with various compartment geometries and a novel two‐step seeding protocol are used to study vessel sprouting decisions. Endothelial cells first organize into hollow vessels tracing the shape contour with high fidelity. Subsequent sprouts emerge in specific directions, responding to compartment geometry. Time‐lapse imaging is used to track vessel migration, evidencing that sprouts frequently emerge from the side centers, mainly migrating toward opposing corners, where the density of support cells (SCs) is the highest, providing the highest levels of angiogenic factors. SCs distribution is quantified by smooth muscle actin expression, confirming the cells preference for curved compartment surfaces and corners. Displacements within the hydrogel correlate with SCs distribution during the initial tubulogenesis phase. This work provides new insight regarding vessel sprouting decisions that should be considered when designing scaffolds for vascularized engineered tissues.     

3D Printing of Multifunctional Hydrogels

3D printing technology has been widely explored for the rapid design and fabrication of hydrogels, as required by complicated soft structures and devices. Here, a new 3D printing method is presented based on the rheology modifier of Carbomer for direct ink writing of various functional hydrogels. Carbomer is shown to be highly efficient in providing ideal rheological behaviors for multifunctional hydrogel inks, including double network hydrogels, magnetic hydrogels, temperature‐sensitive hydrogels, and biogels, with a low dosage (at least 0.5% w/v) recorded. Besides the excellent printing performance, mechanical behaviors, and biocompatibility, the 3D printed multifunctional hydrogels enable various soft devices, including loadable webs, soft robots, 4D printed leaves, and hydrogel Petri dishes. Moreover, with its unprecedented capability, the Carbomer‐based 3D printing method opens new avenues for bioprinting manufacturing and integrated hydrogel devices.     

Electrically Conductive Hydrogel Nerve Guidance Conduits for Peripheral Nerve Regeneration

Peripheral nerve injuries are serious conditions, and surgical treatment has critical limitations. Therefore, nerve guidance conduits (NGCs) are proposed as an alternative. In this study, multifunctional NGCs are fabricated for the regeneration of injured peripheral nerves. Graphene oxide (GO) and gelatin‐methacrylate (GelMA) are polymerized and chemically reduced to form reduced (GO/GelMA) (r(GO/GelMA)). The prepared materials present good electrical conductivity, flexibility, mechanical stability, and permeability, which are suitable for use as NGCs. In vitro studies show 2.1‐ and 1.4‐fold promotion of neuritogenesis of PC12 neuronal cells on r(GO/GelMA) compared to GelMA and unreduced GO/GelMA, respectively. Animal studies using a rat sciatic nerve injury model with a 10 mm gap between the proximal and distal regions of the defect reveal that r(GO/GelMA) NGCs significantly enhance peripheral nerve regeneration, indicated by improved muscle weight increase, electro‐conduction velocity, and sciatic nerve function index. Specifically, r(GO/GelMA) NGCs are utilized to potentiate regrowth with myelination in rat sciatic nerves followed by histological, immunohistological, and morphometrical analyses. This study successfully shows the feasibility of electrically conductive hydrogel NGCs as functional conduits for improved nerve regeneration in a preclinical study, where these NGCs can not only mimic nerve tissues but also strongly promote nerve regeneration.     

Rapid Construction of 3D Biomimetic Capillary Networks with Complex Morphology Using Dynamic Holographic Processing

Microvascular networks (MVNs) are crucial transportation systems in living creatures for nutrient distribution, fluid flow, energy transportation and so on. However, artificial manufacturing of MVNs, especially capillary networks with diameters (average 6 ≈ 9 µm), has always been a problem and bottleneck in tissue engineering due to the lack of efficient manufacturing methods. Herein, a dynamic holographic processing method is reported for producing 3D capillary networks with complex biomimetic morphologies. Combining the axial scanning of the focused beam and the dynamic display of holograms, biomimetic bifurcated microtubes, and porous microtubes with programmable morphologies are rapidly produced by two-photon polymerization (TPP). As a proof-of-concept demonstration, porous microtubes are used as 3D capillary network scaffolds for culturing human umbilical vein endothelial cells (HUVECs) to facilitate the exchange of nutrients and metabolites. Endothelial cells around the vascular scaffolds manifest obvious tight connections and 3D coverage after 3 days in vitro, which reveals that the scaffolds play a significant role in the morphology of dense vascularization. This flexible and rapid method of producing capillary networks provides a versatile platform for vascular physiology, tissue regeneration, and other biomedical areas.     

Inherent Photodegradability of Polymethacrylate Hydrogels: Straightforward Access to Biocompatible Soft Microstructures

Hydrogels are important functional materials useful for 3D cell culture, tissue engineering, 3D printing, drug delivery, sensors, or soft robotics. The ability to shape hydrogels into defined 3D structures, patterns, or particles is crucial for biomedical applications. Here, the rapid photodegradability of commonly used polymethacrylate hydrogels is demonstrated without the need to incorporate additional photolabile functionalities. Hydrogel degradation depths are quantified with respect to the irradiation time, light intensity, and chemical composition. It can be shown that these parameters can be utilized to control the photodegradation behavior of polymethacrylate hydrogels. The photodegradation kinetics, the change in mechanical properties of polymethacrylate hydrogels upon UV irradiation, as well as the photodegradation products are investigated. This approach is then exploited for microstructuring and patterning of hydrogels including hydrogel gradients as well as for the formation of hydrogel particles and hydrogel arrays of well‐defined shapes. Cell repellent but biocompatible hydrogel microwells are fabricated using this method and used to form arrays of cell spheroids. As this method is based on readily available and commonly used methacrylates and can be conducted using cheap UV light sources, it has vast potential to be applied by laboratories with various backgrounds and for diverse applications.     

Bioinspired Development of an In Vitro Engineered Fracture Callus for the Treatment of Critical Long Bone Defects

Cell-based regenerative constructs provide hope for the restoration of tissue function in compromised biological conditions such as complex bone defects. A strategy mimicking the cascade of events of postnatal fracture healing suggests an implant design where progenitor cells provide the driving force for the construct's tissue forming capacity, while framing biomaterials provide cells with 3D cues to direct cellular processes. Large bone defects mainly heal through the formation of an intermediate endochondral fracture callus. The authors aimed to develop an in vitro engineered fracture callus manufactured by bioprinting to provide a spatially organized tissue construct based on: i) in vitro 3D primed human periosteum derived cells and ii) biocompatible thiol-ene alginate hydrogels, mimicking the cells and extracellular matrix present in the different zones of the callus. Cell viability and maintained osteochondrogenic differentiation upon bioprinting is confirmed in vitro. In vivo assessment displays that the developed biomaterials provided essential 3D cues that further guided the cells in their tissue forming process in the absence of additional stimulatory molecules. The reported findings confirm the appeal of a biomimetic approach to steer tissue development of in vitro engineered constructs and illustrate the suitability of bioprinting methodologies for the fabrication of living regenerative implants.     

Growth‐Factor Free Multicomponent Nanocomposite Hydrogels That Stimulate Bone Formation

Synthetic osteo‐promoting materials that are able to stimulate and accelerate bone formation without the addition of exogenous cells or growth factors represent a major opportunity for an aging world population. A co‐assembling system that integrates hyaluronic acid tyramine ( HA‐Tyr ), bioactive peptide amphiphiles ( GHK‐Cu²⁺ ), and Laponite ( Lap ) to engineer hydrogels with physical, mechanical, and biomolecular signals that can be tuned to enhance bone regeneration is reported. The central design element of the multicomponent hydrogels is the integration of self‐assembly and enzyme‐mediated oxidative coupling to optimize structure and mechanical properties in combination with the incorporation of an osteo‐ and angio‐promoting segments to facilitate signaling. Spectroscopic techniques are used to confirm the interplay of orthogonal covalent and supramolecular interactions in multicomponent hydrogel formation. Furthermore, physico‐mechanical characterizations reveal that the multicomponent hydrogels exhibit improved compressive strength, stress relaxation profile, low swelling ratio, and retarded enzymatic degradation compared to the single component hydrogels. Applicability is validated in vitro using human mesenchymal stem cells and human umbilical vein endothelial cells, and in vivo using a rabbit maxillary sinus floor reconstruction model. Animals treated with the HA‐Tyr‐HA‐Tyr‐GHK‐Cu²⁺ hydrogels exhibit significantly enhanced bone formation relative to controls including the commercially available Bio‐Oss.     

3D Printing of Strong and Tough Double Network Granular Hydrogels

Many soft natural tissues display a fascinating set of mechanical properties that remains unmatched by manmade counterparts. These unprecedented mechanical properties are achieved through an intricate interplay between the structure and locally varying the composition of these natural tissues. This level of control cannot be achieved in soft synthetic materials. To address this shortcoming, a novel 3D printing approach to fabricate strong and tough soft materials is introduced, namely double network granular hydrogels (DNGHs) made from compartmentalized reagents. This is achieved with an ink composed of microgels that are swollen in a monomer-containing solution; after the ink is additive manufactured, these monomers are converted into a percolating network, resulting in a DNGH. These DNGHs are sufficiently stiff to repetitively support tensile loads up to 1.3 MPa. Moreover, they are more than an order of magnitude tougher than each of the pure polymeric networks they are made from. It is demonstrated that this ink enables printing macroscopic, strong, and tough objects, which can optionally be rendered responsive, with high shape fidelity. The modular and robust fabrication of DNGHs opens up new possibilities to design adaptive, strong, and tough hydrogels that have the potential to advance, for example, soft robotic applications.     

A Hybrid Peptide Amphiphile Fiber PEG Hydrogel Matrix for 3D Cell Culture

Since the traditional 2D surface for cell growth has been shown to be increasingly insufficient in contemporary cell biology, more and more research is performed on 3D matrices that can better represent the natural extracellular matrix (ECM) in many aspects. To create such a complex nonuniform 3D matrix, four‐armed polyethylene glycol with azides and (1R,8S,9S)‐bicyclo[6.1.0]non‐4‐yn‐9‐yl groups is functionalized to form the hydrogel basis. Together with these, a matrix metalloproteinase cleavable peptide sequence as a functional motif is also built in to add degradability to the hydrogel. In addition, self‐assembled peptide amphiphile (PA) fibers containing a cellular binding peptide sequence (RGDS) are encapsulated in the hydrogel to mimic the natural fibrous structure of the ECM and to stimulate cell adhesion. Rheology studies confirm that the polymer dissolved in the PA fiber solution forms a stable hydrogel with acceptable mechanical properties (G′ = 3.8 kPa). In addition, it is shown that this hydrogel network is degradable under the action of a metalloproteinase enzyme. Finally, the hybrid hydrogel is used to culture and it is demonstrated that both HeLa cells and human mesenchymal stem cells show adherence, good viability, and a well‐spread shape inside the hybrid hydrogel after 5 days of incubation when all components are present.     

3D‐Printed Soft Magnetoelectric Microswimmers for Delivery and Differentiation of Neuron‐Like Cells

Neurodegenerative diseases generally result in irreversible neuronal damage and neuronal death. Cell therapy shows promise as a potential treatment for these diseases. However, the therapeutic targeted delivery of these cells and the in situ provision of a suitable microenvironment for their differentiation into functional neuronal networks remain challenging. A highly integrated multifunctional soft helical microswimmer featuring targeted neuronal cell delivery, on‐demand localized wireless neuronal electrostimulation, and post‐delivery enzymatic degradation is introduced. The helical soft body of the microswimmer is fabricated by two‐photon lithography of the photocurable gelatin–methacryloyl (GelMA)‐based hydrogel. The helical body is then impregnated with composite multiferroic nanoparticles displaying magnetoelectric features (MENPs). While the soft GelMA hydrogel chassis supports the cell growth, and is degraded by enzymes secreted by cells, the MENPs allow for the magnetic transportation of the bioactive chassis, and act as magnetically mediated electrostimulators of neuron‐like cells. The unique combination of the materials makes these microswimmers highly integrated devices that fulfill several requirements for their future translation to clinical applications, such as cargo delivery, cell stimulation, and biodegradability. The authors envision that these devices will inspire new avenues for targeted cell therapies for traumatic injuries and diseases in the central nervous system.     

Microgel Assembly Powder Improves Acute Hemostasis,Antibacterial, and Wound Healing via In Situ Co-Assembly of Erythrocyte and Microgel

Rapid and effective hemostasis on irregular-shaped non-compressible bleeding wounds is still one of the key challenges in clinical practice. Herein, a novel multi-functional microgel assembly powder (MAP) composed of oxidized dextran/methacrylate gelatin (ODex/GelMA) microgel powder and long-chain alkyl quaternized chitosan (LQCS) crosslinker powder is reported for acute hemostasis, antibacterial, and wound healing. When MAP is applied onto bleeding wounds, porous ODex/GelMA microgel powder immediately absorbs massive liquid in blood whilst LQCS induces in situ co-assembly of erythrocytes and microgels. In other words, MAP combines the merits of hemostatic powders and hemostatic hydrogels, that is, the excellent hemostasis performance of MAP is originated from not only the high fluid uptake ratio/rate that causes the aggregation of coagulation factors and erythrocytes, but also the formation of erythrocytes-involved hydrogel-like microgel assembly that dramatically improves the mechanical strength, tissue adhesion and wound sealing performance in blood compared with those in PBS. In addition, MAP also exhibits excellent antibacterial ability, and promotes the wound healing in bacterial-infected full-thickness skin wounds. The fantastic features of MAP including low cost, easy synthesis and usage, excellent hemostasis on irregular-shaped, non-compressible bleeding wounds, outstanding antibacterial and wound healing, good cytocompatibility, make it a promising hemostatic material and wound dressing.