Poly(dehydroalanine)-Based Hydrogels as Efficient Soft Matter Matrices for Light-Driven Catalysis.

Soft matter integration of photosensitizers and catalysts provides promising solutions to developing sustainable materials for energy conversion. Particularly, hydrogels bring unique benefits, such as spatial control and 3D-accessibility of molecular units, as well as recyclability. Herein, the preparation of polyampholyte hydrogels based on poly(dehydroalanine) (PDha) is reported. Chemically crosslinked PDha with bis-epoxy poly(ethylene glycol) leads to a transparent, self-supporting hydrogel. Due to the ionizable groups on PDha, this 3D polymeric matrix can be anionic, cationic, or zwitterionic depending on the pH value, and its high density of dynamic charges has a potential for electrostatic attachment of charged molecules. The integration of the cationic molecular photosensitizer [Ru(bpy)3 ]2+ (bpy = 2,2'-bipyridine) is realized, which is a reversible process controlled by pH, leading to light harvesting hydrogels. They are further combined with either a thiomolybdate catalyst ([Mo3 S13 ]2- ) for hydrogen evolution reaction (HER) or a cobalt polyoxometalate catalyst (Co4 POM = [Co4 (H2 O)2 (PW9 O34 )2 ]10- ) for oxygen evolution reaction (OER). Under the optimized condition, the resulting hydrogels show catalytic activity in both cases upon visible light irradiation. In the case of OER, higher photosensitizer stability is observed compared to homogeneous systems, as the polymer environment seems to influence decomposition pathways.

Nanoenzyme-Reinforced Multifunctional Scaffold Based on Ti3C2Tx MXene Nanosheets for Promoting Structure-Functional Skeletal Muscle Regeneration via Electroactivity and Microenvironment Management.

The completed volumetric muscle loss (VML) regeneration remains a challenge due to the limited myogenic differentiation as well as the oxidative, inflammatory, and hypoxic microenvironment. Herein, a 2D Ti3C2Tx MXene@MnO2 nanocomposite with conductivity and microenvironment remodeling was fabricated and applied in developing a multifunctional hydrogel (FME) scaffold to simultaneously conquer these hurdles. Among them, Ti3C2Tx MXene with electroconductive ability remarkably promotes myogenic differentiation via enhancing the myotube formation and upregulating the relative expression of the myosin heavy chain (MHC) protein and myogenic genes (MyoD and MyoG) in myogenesis. The MnO2 nanoenzyme-reinforced Ti3C2Tx MXene significantly reshapes the hostile microenvironment by eliminating reactive oxygen species (ROS), regulating macrophage polarization from M1 to M2 and continuously supplying O2. Together, the FME hydrogel as a bioactive multifunctional scaffold significantly accelerates structure-functional VML regeneration in vivo and represents a multipronged strategy for the VML regeneration via electroactivity and microenvironment management.

A method for reproducible high-resolution imaging of 3D cancer cell spheroids.

Multicellular tumour cell spheroids embedded within three-dimensional (3D) hydrogels or extracellular matrices (ECM) are widely used as models to study cancer growth and invasion. Standard methods to embed spheroids in 3D matrices result in random placement in space which limits the use of inverted fluorescence microscopy techniques, and thus the resolution that can be achieved to image molecular detail within the intact spheroid. Here, we leverage UV photolithography to microfabricate PDMS (polydimethylsiloxane) stamps that allow for generation of high-content, reproducible well-like structures in multiple different imaging chambers. Addition of multicellular tumour spheroids into stamped collagen structures allows for precise positioning of spheroids in 3D space for reproducible high-/super-resolution imaging. Embedded spheroids can be imaged live or fixed and are amenable to immunostaining, allowing for greater flexibility of experimental approaches. We describe the use of these spheroid imaging chambers to analyse cell invasion, cell-ECM interaction, ECM alignment, force-dependent intracellular protein dynamics and extension of fine actin-based protrusions with a variety of commonly used inverted microscope platforms. This method enables reproducible, high-/super-resolution live imaging of multiple tumour spheroids, that can be potentially extended to visualise organoids and other more complex 3D in vitro systems.

Directional Submicrofiber Hydrogel Composite Scaffolds Supporting Neuron Differentiation and Enabling Neurite Alignment.

Cell cultures aiming at tissue regeneration benefit from scaffolds with physiologically relevant elastic moduli to optimally trigger cell attachment, proliferation and promote differentiation, guidance and tissue maturation. Complex scaffolds designed with guiding cues can mimic the anisotropic nature of neural tissues, such as spinal cord or brain, and recall the ability of human neural progenitor cells to differentiate and align. This work introduces a cost-efficient gelatin-based submicron patterned hydrogel-fiber composite with tuned stiffness, able to support cell attachment, differentiation and alignment of neurons derived from human progenitor cells. The enzymatically crosslinked gelatin-based hydrogels were generated with stiffnesses from 8 to 80 kPa, onto which poly(ε-caprolactone) (PCL) alignment cues were electrospun such that the fibers had a preferential alignment. The fiber-hydrogel composites with a modulus of about 20 kPa showed the strongest cell attachment and highest cell proliferation, rendering them an ideal differentiation support. Differentiated neurons aligned and bundled their neurites along the aligned PCL filaments, which is unique to this cell type on a fiber-hydrogel composite. This novel scaffold relies on robust and inexpensive technology and is suitable for neural tissue engineering where directional neuron alignment is required, such as in the spinal cord.

Thermosensitive quaternized chitosan hydrogel scaffolds promote neural differentiation in bone marrow mesenchymal stem cells and functional recovery in a rat spinal cord injury model.

A thermosensitive quaternary ammonium chloride chitosan/ß-glycerophosphate (HACC/ß-GP) hydrogel scaffold combined with bone marrow mesenchymal stem cells (BMSCs) transfected with an adenovirus containing the glial cell-derived neurotrophic factor (GDNF) gene (Ad-rGDNF) was applied to spinal cord injury (SCI) repair. The BMSCs from rats were transfected with Ad-rGDNF, resulting in the expression of GDNF mRNA in the BMSCs increasing and their spontaneous differentiation into neural-like cells expressing neural markers such as NF-200 and GFAP. After incubation with HACC/ß-GP hydrogel scaffolds for 2 weeks, neuronal differentiation of the BMSCs was confirmed using immunofluorescence (IF), and the expression of GDNF by the BMSCs was detected by Western blot at different time points. MTT assay and scanning electron microscopy confirmed that the HACC scaffold provides a non-cytotoxic microenvironment that supports cell adhesion and growth. Rats with SCI were treated with BMSCs, BMSCs carried by the HACC/ß-GP hydrogel (HACC/BMSCs), Ad-rGDNF-BMSCs, or Ad-rGDNF-BMSCs carried by the hydrogel (HACC/GDNF-BMSCs). Animals were sacrificed at 2, 4, and 6 weeks of treatment. IF staining and Western blot were performed to detect the expression of NeuN, NF-200, GFAP, CS56, and Bax in the lesion sites of the injured spinal cord. Upon treatment with HACC/BMSCs, NF200 and GFAP were upregulated but CS56 and Bax were downregulated in the SCI lesion site. Furthermore, transplantation of HACC/GDNF-BMSCs into an SCI rat model significantly improved BBB scores and regeneration of the spinal cord. Thus, HACC/ß-GP hydrogel scaffolds show promise for functional recovery in spinal cord injury patients.

Characterizing the dynamic rheology in the pericellular region by human mesenchymal stem cell re-engineering in PEG-peptide hydrogel scaffolds.

During wound healing, human mesenchymal stem cells (hMSCs) migrate to injuries to regulate inflammation and coordinate tissue regeneration. To enable migration, hMSCs re-engineer the extracellular matrix rheology. Our work determines the correlation between cell engineered rheology and motility. We encapsulate hMSCs in a cell-degradable peptide-polymeric hydrogel and characterize the change in rheological properties in the pericellular region using multiple particle tracking microrheology. Previous studies determined that pericellular rheology is correlated with motility. Additionally, hMSCs re-engineer their microenvironment by regulating cell-secreted enzyme, matrix metallopro-teinases (MMPs), activity by also secreting their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). We independently inhibit TIMPs and measure two different degradation profiles, reaction-diffusion and reverse reaction-diffusion. These profiles are correlated with cell spreading, speed and motility type. We model scaffold degradation using Michaelis-Menten kinetics, finding a decrease in kinetics between joint and independent TIMP inhibition. hMSCs ability to regulate microenvironmental remodeling and motility could be exploited in design of new materials that deliver hMSCs to wounds to enhance healing.

A sustainable strategy for generating highly stable human skin equivalents based on fish collagen.

Tissue engineered skin equivalents are increasingly recognized as potential alternatives to traditional skin models such as human ex vivo skin or animal skin models. However, most of the currently investigated human skin equivalents (HSEs) are constructed using mammalian collagen which can be expensive and difficult to extract. Fish skin is a waste product produced by fish processing industries and identified as a cost-efficient and sustainable source of type I collagen. In this work, we describe a method for generating highly stable HSEs based on fibrin fortified tilapia fish collagen. The fortified fish collagen (FFC) formulation is optimized to enable reproducible fabrication of full-thickness HSEs that undergo limited contraction, facilitating the incorporation of human donor-derived skin cells and formation of biomimetic dermal and epidermal layers. The morphology and barrier function of the FFC HSEs are compared with a commercial skin model and validated with immunohistochemical staining and transepithelial electrical resistance testing. Finally, the potential of a high throughput screening platform with FFC HSE is explored by scaling down its fabrication to 96-well format.

Advances in Microfluidic Technologies in Organoid Research.

Organoids have emerged as major technological breakthroughs and novel organ models that have revolutionized biomedical research by recapitulating the key structural and functional complexities of their in vivo counterparts. The combination of organoid systems and microfluidic technologies has opened new frontiers in organoid engineering and offers great opportunities to address the current challenges of existing organoid systems and broaden their biomedical applications. In this review, the key features of the existing organoids, including their origins, development, design principles, and limitations, are described. Then the recent progress in integrating organoids into microfluidic systems is highlighted, involving microarrays for high-throughput organoid manipulation, microreactors for organoid hydrogel scaffold fabrication, and microfluidic chips for functional organoid culture. The opportunities in the nascent combination of organoids and microfluidics that lie ahead to accelerate research in organ development, disease studies, drug screening, and regenerative medicine are also discussed. Finally, the challenges and future perspectives in the development of advanced microfluidic platforms and modified technologies for building organoids with higher fidelity and standardization are envisioned.

A Zn2+ cross-linked sodium alginate/epigallocatechin gallate hydrogel scaffold for promoting skull repair.

The optimal material for repairing skull defects should exhibit outstanding biocompatibility and mechanical properties. Specifically, hydrogel scaffolds that emulate the microenvironment of the native bone extracellular matrix play a vital role in promoting osteoblast adhesion, proliferation, and differentiation, thereby yielding superior outcomes in skull reconstruction. In this study, a composite network hydrogel comprising sodium alginate (SA), epigallocatechin gallate (EGCG), and zinc ions (Zn2+) was developed to establish an ideal osteogenic microenvironment for bone regeneration. Initially, physical entanglement and hydrogen bonding between SA and EGCG resulted in the formation of a primary network hydrogel known as SA-EGCG. Subsequently, the inclusion of Zn2+ facilitated the creation of a composite network hydrogels named SA-EGCG-Zn2+ via dynamic coordination bonds with SA and EGCG. The engineered SA-EGCG2 %-Zn2+ hydrogels offered an environment mimicking the native extracellular matrix (ECM). Moreover, the sustained release of Zn2+ from the hydrogel effectively enhanced cell adhesion, promoted proliferation, and stimulated osteoblast differentiation. In vitro experiments have shown that SA-EGCG2 %-Zn2+ hydrogels greatly enhance the attachment and growth of osteoblast precursor cells (MC3T3-E1), while also increasing the expression of genes related to osteogenesis in these cells. Additionally, in vivo studies have confirmed that SA-EGCG2 %-Zn2+ hydrogels promote new bone formation and accelerate the regeneration of bone in situ, indicating promising applications in the realm of bone tissue engineering.

Vascularization ability of glioma stem cells in different three-dimensional microenvironments.

Glioblastoma (GBM) is among the most common and aggressive adult central nervous system tumors. One prominent characteristic of GBM is the presence of abnormal microvessels. A significant correlation between angiogenesis and prognosis has been observed. Accurately reconstructing this neovascularization and tumor microenvironment through personalized in vitro disease models presents a significant challenge. However, it is crucial to develop new anti-angiogenic therapies for GBM. In this study, 3D bioprinted glioma stem cell (GSC)-laden hydrogel scaffolds, hybrid GSC hydrogels and cell-free hydrogel scaffolds were manufactured to investigate the vascularization ability of GSCs in varying 3D microenvironments. Our results demonstrated that the bioactivity of GSCs in the 3D bioprinted GSC-laden hydrogel scaffold was preferable and stable, and the amounts of vascular endothelial growth factor A and basic fibroblast growth factor were the highest in the microenvironment. When the three different models were co-cultured with human umbilical vein endothelial cells, the expression of angiogenesis-related markers was the most abundant in the bioprinted GSC-laden hydrogel scaffold. Additionally, xenograft tumors formed by bioprinted GSC-laden hydrogel scaffolds more closely resembled human gliomas regarding color, texture and vascularization. Notably, in xenograft tumors derived from 3D bioprinted GSC-laden hydrogel scaffolds, the number of human CD105+ cells was significantly higher, and human endothelial vascular lumen-like structures were observed. This indicates that the 3D bioprinted GSC-laden hydrogel scaffold is a suitable model for mimicking the glioma microenvironment and studying tumor angiogenesis.

Reasoning on Pore Terminology in 3D Bioprinting.

Terminology is pivotal for facilitating clear communication and minimizing ambiguity, especially in specialized fields such as chemistry. In materials science, a subset of chemistry, the term "pore" is traditionally linked to the International Union of Pure and Applied Chemistry (IUPAC) nomenclature, which categorizes pores into "micro", "meso", and "macro" based on size. However, applying this terminology in closely-related areas, such as 3D bioprinting, often leads to confusion owing to the lack of consensus on specific definitions and classifications tailored to each field. This review article critically examines the current use of pore terminology in the context of 3D bioprinting, highlighting the need for reassessment to avoid potential misunderstandings. We propose an alternative classification that aligns more closely with the specific requirements of bioprinting, suggesting a tentative size-based division of interconnected pores into 'parvo'-(d < 25 µm), 'medio'-(25 < d < 100 µm), and 'magno'-(d > 100 µm) pores, relying on the current understanding of the pore size role in tissue formation. The introduction of field-specific terminology for pore sizes in 3D bioprinting is essential to enhance the clarity and precision of research communication. This represents a step toward a more cohesive and specialized lexicon that aligns with the unique aspects of bioprinting and tissue engineering.

Fabrication of Fish Scale-Based Gelatin Methacryloyl for 3D Bioprinting Application.

Gelatin methacryloyl (GelMA) is an ideal bioink that is commonly used in bioprinting. GelMA is primarily acquired from mammalian sources; however, the required amount makes the market price extremely high. Since garbage overflow is currently a global issue, we hypothesized that fish scales left over from the seafood industry could be used to synthesize GelMA. Clinically, the utilization of fish products is more advantageous than those derived from mammals as they lower the possibility of disease transmission from mammals to humans and are permissible for practitioners of all major religions. In this study, we used gelatin extracted from fish scales and conventional GelMA synthesis methods to synthesize GelMA, then tested it at different concentrations in order to evaluated and compared the mechanical properties and cell responses. The fish scale GelMA had a printing accuracy of 97%, a swelling ratio of 482%, and a compressive strength of about 85 kPa at a 10% w/v GelMA concentration. Keratinocyte cells (HaCaT cells) were bioprinted with the GelMA bioink to assess cell viability and proliferation. After 72 h of culture, the number of cells increased by almost three-fold compared to 24 h, as indicated by many fluorescent cell nuclei. Based on this finding, it is possible to use fish scale GelMA bioink as a scaffold to support and enhance cell viability and proliferation. Therefore, we conclude that fish scale-based GelMA has the potential to be used as an alternative biomaterial for a wide range of biomedical applications.

Study of mechanical property and biocompatibility of graphene oxide/MEO2MA hydrogel scaffold for wound healing application.

Wound healing is a complex biological process crucial for restoring tissue integrity and preventing infections. The development of advanced materials that facilitate and expedite the wound-healing process has been a focal point in biomedical research. In this study, we aimed to enhance the wound-healing potential of hydrogel scaffolds by incorporating graphene oxide and poly (ethylene glycol) methyl ether methacrylate (MEO2MA). Various masses of graphene oxide were added to MEO2MA hydrogels via free radical polymerisation. Comprehensive characterizations, encompassing mechanical properties, and biocompatibility assays, were conducted to evaluate the hydrogels' suitability for wound healing. In vitro experiments demonstrated that the graphene oxide-based hydrogels exhibited a proper swelling degree and tensile strength, responding effectively to moisture conditions and adhesiveness for wound healing. Notably, the tensile strength significantly increased to 626 kPa in the graphene oxide hydrogels. Biocompatibility assessments revealed that the graphene oxide/MEO2MA hydrogels were non-toxic to human dermal fibroblast cell growth, with no significant difference in cell viability observed in the graphene oxide/MEO2MA hydrogel (H-HG) group. In a rat skin experiment, the wound-healing rate of the hydrogel incorporating graphene oxide surpassed that of the pristine hydrogel after a 15-day treatment, achieving over 95% wound closure in the H-HG group. The histopathological analysis further supported the efficacy of the H-HG hydrogel dressing in promoting more effective tissue regeneration. These results collectively highlight the potential of the graphene oxide/MEO2MA hydrogel scaffold as a promising dressing for medical applications.

Localized delivery of metformin via 3D printed GelMA-Nanoclay hydrogel scaffold for enhanced treatment of diabetic bone defects.

Background: Diabetic bone defects present significant challenges for individuals with diabetes. While metformin has been explored for bone regeneration via local delivery, its application in treating diabetic bone defects remains under-explored. In this study, we aim to leverage 3D printing technology to fabricate a GelMA-Nanoclay hydrogel scaffold loaded with metformin specifically for this purpose. The objective is to assess whether the in situ release of metformin can effectively enhance osteogenesis, angiogenesis, and immunomodulation in the context of diabetic bone defects. Materials and methods: Utilizing 3D printing technology, we constructed a GelMA-Nanoclay-Metformin hydrogel scaffold with optimal physical properties and biocompatibility. The osteogenic, angiogenic, and immunomodulatory characteristics of the hydrogel scaffold were thoroughly investigated through both in vitro and in vivo experiments. Results: GelMA10%-Nanoclay8%-Metformin5mg/mL was selected as the bioink for 3D printing due to its favorable swelling rate, degradation rate, mechanical strength, and drug release rate. Through in vitro investigations, the hydrogel scaffold extract, enriched with metformin, demonstrated a substantial enhancement in the proliferation and migration of BMSCs within a high-glucose microenvironment. It effectively enhances osteogenesis, angiogenesis, and immunomodulation. In vivo experimental outcomes further underscored the efficacy of the metformin-loaded GelMA-Nanoclay hydrogel scaffold in promoting superior bone regeneration within diabetic bone defects. Conclusions: In conclusion, while previous studies have explored local delivery of metformin for bone regeneration, our research is pioneering in its application to diabetic bone defects using a 3D printed GelMA-Nanoclay hydrogel scaffold. This localized delivery approach demonstrates significant potential for enhancing bone regeneration in diabetic patients, offering a novel approach for treating diabetic bone defects. The translational potential of this article: Our study demonstrates, for the first time, the successful loading of the systemic antidiabetic drug metformin onto a hydrogel scaffold for localized delivery. This approach exhibits significant efficacy in mending diabetic bone defects, presenting a promising new avenue for the treatment of such conditions.

Self-assembling peptide hydrogel scaffold integrating stem cell-derived exosomes for infected bone defects.

Infected bone defect (IBD) is a great challenge in orthopedics, which involves in bone loss and infection. Here, a self-assembling hydrogel scaffold (named AMP-RAD/EXO), integrating antimicrobial peptides(AMPs), RADA16 and BMSCs exosomes with an innovative strategy, is developed and applied in IBD treatment for sustained antimicrobial ability, accelerating osteoblasts proliferation and promoting bone regeneration. AMPs present an excellent ability to inhibit infection, RADA16 is a self-assembling peptide hydrogel for AMPs delivery, and BMSCs exosomes can promote the bone regeneration. The prepared AMP-RAD/EXO exhibited a polyporous 3D structure for imbibition of BMSCs exosomes and migration of osteoblasts. In vitro studies indicate AMP-RAD/EXO can inhibit the growth of Staphylococcus aureus, accelerate the proliferation and migration of BMSCs. More importantly, in vivo results also prove that AMP-RAD/EXO exhibit an excellent effect on IBD treatment. Thus, the prepared AMP-RAD/EXO provides a multifunctional scaffold concept for bone tissue engineering technology.

Evaluation puramatrix as a 3D microenvironment for neural differentiation of human breastmilk stem cells.

The extracellular matrix is recognized as an efficient and determining component in the growth, proliferation, and differentiation of cells due to its ability to perceive and respond to environmental signals. Applying three-dimensional scaffolds can create conditions similar to the extracellular matrix and provide an opportunity to investigate cell fate. In this study, we employed the PuraMatrix hydrogel scaffold as an advanced cell culture platform for the neural differentiation of stem cells derived from human breastmilk to design an opportune model for tissue engineering. Isolated stem cells from breastmilk were cultured and differentiated into neural-like cells on PuraMatrix peptide hydrogel and in the two-dimensional system. The compatibility of breastmilk-derived stem cells with PuraMatrix and cell viability was evaluated by scanning electron microscopy and MTT assay, respectively. Induction of differentiation was achieved by exposing cells to the neurogenic medium. After 21 days of the initial differentiation process, the expression levels of glial fibrillary acidic protein (GFAP), microtubule-associated protein (MAP2), ß-tubulin III, and neuronal nuclear antigen (NeuN) were analyzed using the immunostaining technique. The results illustrated a notable expression of MAP2, ß-tubulin-III, and NeuN in the three-dimensional cell culture in comparison to the two-dimensional system, indicating the beneficial effect of PuraMatrix scaffolds in the process of differentiating breastmilk-derived stem cells into neural-like cells. In view of the obtained results, the combination of breastmilk-derived stem cells and PuraMatrix hydrogel scaffold could be an advisable preference for neural tissue regeneration and cell therapy.

Dual-Targeted Metal Ion Network Hydrogel Scaffold for Promoting the Integrated Repair of Tendon-Bone Interfaces.

The tendon-bone interface has a complex gradient structure vital for stress transmission and pressure buffering during movement. However, injury to the gradient tissue, especially the tendon and cartilage components, often hinders the complete restoration of the original structure. Here, a metal ion network hydrogel scaffold, with the capability of targeting multitissue, was constructed through the photopolymerization of the LHERHLNNN peptide-modified zeolitic imidazolate framework-8 (LZIF-8) and the WYRGRL peptide-modified magnesium metal-organic framework (WMg-MOF) within the hydrogel scaffold, which could facilitate the directional migration of metal ions to form a dynamic gradient, thereby achieving integrated regeneration of gradient tissues. LZIF-8 selectively migrated to the tendon, releasing zinc ions to enhance collagen secretion and promoting tendon repair. Simultaneously, WMg-MOF migrated to cartilage, releasing magnesium ions to induce cell differentiation and facilitating cartilage regeneration. Infrared spectroscopy confirmed successful peptide modification of nano ZIF-8 and Mg-MOF. Fluorescence imaging validated that LZIF-8/WMg-MOF had a longer retention, indirectly confirming their successful targeting of the tendon-bone interface. In summary, this dual-targeted metal ion network hydrogel scaffold has the potential to facilitate synchronized multitissue regeneration at the compromised tendon-bone interface, offering favorable prospects for its application in the integrated reconstruction characterized by the gradient structure.

An ultrasound-triggered injectable sodium alginate scaffold loaded with electrospun microspheres for on-demand drug delivery to accelerate bone defect regeneration.

Biological processes, such as bone defects healing are precisely controlled in both time and space. This spatiotemporal characteristic inspires novel therapeutic strategies. The sustained-release systems including hydrogels are commonly utilized in the treatment of bone defect; however, traditional hydrogels often release drugs at a consistent rate, lacking temporal precision. In this study, a hybrid hydrogel has been developed by using sodium alginate, sucrose acetate isobutyrate, and electrospray microspheres as the base materials, and designed with ultrasound response, and on-demand release properties. Sucrose acetate isobutyrate was added to the hybrid hydrogel to prevent burst release. The network structure of the hybrid hydrogel is formed by the interconnection of Ca2+ with the carboxyl groups of sodium alginate. Notably, when the hybrid hydrogel is exposed to ultrasound, the ionic bond can be broken to promote drug release; when ultrasound is turned off, the release returned to a low-release state. This hybrid hydrogel reveals not only injectability, degradability, and good mechanical properties but also shows multiple responses to ultrasound. And it has good biocompatibility and promotes osteogenesis efficiency in vivo. Thus, this hybrid hydrogel provides a promising therapeutic strategy for the treatment of bone defects.

A composite hydrogel scaffold based on collagen and carboxymethyl chitosan for cartilage regeneration through one-step chemical crosslinking.

The number of cases of cartilage damage worldwide is increasing annually and this problem severely limits an individual's physical activities, subsequently contributing to additional medical problems. Hydrogels can repair cartilage defects and promote cartilage regeneration. In this study, a composite hydrogel scaffold was prepared with collagen (COL), carboxymethyl chitosan (CMC), and the Arg-Gly-Asp (RGD) peptide through one-step chemical crosslinking, in which the three compositions ratio was especially investigated. The hydrogel scaffold performed well in cell adhesion and biocompatibility experiments, mainly due to the favorable porosity (the aperture was concentrated at 100 µm and the porosity was >70 %) and RGD concentration (2 mM RGD was the optimal concentration, which could effectively improve the attachment of BMSCs to the stent). Moreover, bone marrow mesenchymal stem cells (BMSCs) filled in the hydrogel scaffold, together with transforming growth factor TGF-ß3, which was applied to evaluate the feasibility on the repair of the injured cartilage of the rat. In vitro and in vivo study, according to the results of cell proliferation and cytotoxicity, the hydrogel material had no toxic effect on cells, and the COL2/CMC1 hydrogel scaffold had the most obvious role in promoting cell proliferation. The results of pathological section showed that the cell scaffold complex group provided good mechanical properties for the wound and supplemented the stem cells derived from chondrocytes and showed good cartilage defect repair effect; In the scaffold group, the surface fibrosis of the injured area was mainly filled with fibrocartilage and other collagen fibers The hydrogel/BMSCs complex based on COL and CMC can be beneficial for the regeneration of cartilage.