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Abstract Supramolecular peptides exhibit obvious similarities with collagen fibers in terms of self-assembly characteristics, nanofibrous structure, and responsiveness to external stimuli. Here, a series of supramolecular peptides were developed by altering the amino acid sequence, enabling the self-assembly of three types of 4-biphenylacetic acid (BPAA)-tripeptides into fibrous hydrogel through hydrogen bonding and π–π stacking under the influence of ion induction. Transmission electron and scanning electron microscopies revealed that the diameter of the fiber within nanofibrous hydrogels was ~ 10 and ~ 40 nm, respectively, which was similar with the self-assembled collagen fibers. For this reason, these hydrogels could be considered as a biomimetic extracellular substitute. Meanwhile, the gelation concentration induced by ions was even lower than 0.66 wt%, with an elastic modulus of ~ 0.27 kPa, corresponding to a water content of 99.34 wt%. In addition, the three supramolecular hydrogels were found to be good substrates for L929 cell adhesion and MC-3T3 cell proliferation. The overall results implied that BPAA-based hydrogels have a lucrative application potential as cell carriers. Graphical Abstract

Supramolecular peptides exhibit obvious similarities with collagen fibers in terms of self-assembly characteristics, nanofibrous structure, and responsiveness to external stimuli. Here, a series of supramolecular peptides were developed by altering the amino acid sequence, enabling the self-assembly of three types of 4-biphenylacetic acid (BPAA)-tripeptides into fibrous hydrogel through hydrogen bonding and π–π stacking under the influence of ion induction. Transmission electron and scanning electron microscopies revealed that the diameter of the fiber within nanofibrous hydrogels was ~ 10 and ~ 40 nm, respectively, which was similar with the self-assembled collagen fibers. For this reason, these hydrogels could be considered as a biomimetic extracellular substitute. Meanwhile, the gelation concentration induced by ions was even lower than 0.66 wt%, with an elastic modulus of ~ 0.27 kPa, corresponding to a water content of 99.34 wt%. In addition, the three supramolecular hydrogels were found to be good substrates for L929 cell adhesion and MC-3T3 cell proliferation. The overall results implied that BPAA-based hydrogels have a lucrative application potential as cell carriers. [ABSTRACT FROM AUTHOR]

Kidney transplantation remains a pivotal treatment modality for kidney disease, yet its progress is significantly hindered by the scarcity of donor kidneys and ethical dilemmas surrounding their procurement. As organoid technology evolves and matures, the creation of bionic human kidney organoids offers profound potential for advancing kidney disease research, drug nephrotoxicity screening, and regenerative medicine. Nevertheless, current kidney organoid models grapple with limitations such as constrained cellular differentiation, underdeveloped functional structures, and a crucial absence of vascularization. This deficiency in vascularization, in particular, stunts organoid development, restricts their size, diminishes filtration capabilities, and triggers immunoinflammatory responses. Hence, the achievement of vascularization within kidney organoids and the successful establishment of functional microvascular networks constitutes a paramount goal for their future progression. In this review, we provide an overview of recent advancements in biotechnology domains, encompassing organ-on-a-chip technology, biomimetic matrices, and bioprinting, with the aim of catalyzing technological breakthroughs that can enhance the vascularization of kidney organoids and broaden their applicability. These technologies hold the key to unlocking the full potential of kidney organoids as a transformative therapeutic option for kidney disease., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Extracellular matrix (ECM)-based small-diameter vascular grafts (SDVGs, inner diameter (ID) < 6 mm) hold great promise for clinical applications. However, existing ECM-based SDVGs suffer from limited donor availability, complex purification, high cost, and insufficient mechanical properties. SDVGs with ECM-like structure and function, and good mechanical properties were rapidly prepared by optimizing common materials and preparation, which can improve their clinical prospects. Here, we rapidly prepared an electrospinning film-collagen/red blood cell membrane-genipin hydrogel tube (ES-C/Rm-G-ht, ID = 2 mm) by the combination of the cross-linking of genipin, plastic compression, electrospinning, and rolling without a biological adhesive, which had a shorter preparation time of less than 17 h compared to the existing ECM-based SDVGs (preparation time of 4-18 weeks). ES-C/Rm-G-ht exhibited a layered honeycomb-like structure and demonstrated the ECM-like functions to promote the proliferation and migration of endothelial cells, and prevent thrombus and inflammation. Furthermore, ES-C/Rm-G-ht, possessing sufficient mechanical strength, showed high patency, rapid endothelialization (95%), good regeneration of smooth muscle cell layers and ECM, and effective antistenosis capability after implantation in the rabbit's carotid artery for 31 days. This work provides a straightforward, cost-effective, and promising strategy to prepare SDVGs with ECM-like structure and function, which is an ideal alternative for vascular grafts and autologous vessels in the current clinic.

Cartilage regeneration remains a current challenge with no satisfactory strategy in surgery. Hydrogels with structurally and biochemically biomimicking characteristics have been regarded as a promising approach for the success of cartilage regeneration. Naturally sourced hydrogels from exopolysaccharides are ideal candidates for the construction of biomimetic extracellular matrix (ECM) because of their biomimetic networks, high water content, cytocompatibility, and biodegradability. Here, an approach that integrates covalent and ionic bonds in a hydrogel system is shown to form a natural polymeric hydrogel double network (DN) for promoting the adhesion and proliferation of chondrocytes and supporting the formation of matured cartilage tissue. DN hydrogels comprised of chemically crosslinked hyaluronan (HA) and physically crosslinked gellan gum (GG) were developed for potential scaffold fabrication. Compared with HA single network (SN) hydrogel and GG SN hydrogel, the obtained HA/GG DN hydrogel with Young's modulus of 28.6 kPa exhibited adequate compressive strength (208.9 kPa) and high toughness (dissipated energy 2837 J/m3) and thus can be used as a biomimetic extracellular matrix for minimal invasively repairing cartilage. In vitro studies showed that HA/GG DN hydrogel-based ECM promoted the proliferation of chondrocytes. The HA/GG DN hydrogel significantly supported the deposition of cartilage ECM-specific sulfated glycosaminoglycan and type II collagen and facilitated the formation of cartilage tissues. In a rabbit osteochondral defect model, HA/GG DN hydrogel significantly improved cartilage regeneration. The HA/GG DN hydrogel as a biomimetic ECM is a promising candidate as a biomaterial scaffold for cartilage regeneration and repair. The fabrication of a biomaterial scaffold as an artificial extracellular matrix (ECM) for cartilage regeneration remains a big challenge. In this work, we fabricated a double-network (DN) hydrogel based on hyaluronan and gellan gum (HA/GG) through a sequential chemical and physical cross-linking process. The HA/GG DN hydrogel exhibited high compressive strength, high toughness, stiffness, and good self-recovery property. The HA/GG DN hydrogel can support chondrocyte proliferation and new ECM deposition correlated with the enhanced mechanical properties, good cytocompatibility, and biodegradability. In vivo animal experiments demonstrated that this HA/GG DN hydrogel facilitates hyaline-like cartilage regeneration. These findings imply that the developed HA/GG DN hydrogel as a biomimetic ECM offers a hopeful new platform for cartilage tissue engineering. [Display omitted] [ABSTRACT FROM AUTHOR]

The development of biomimetic extracellular matrix (ECM) with fibrous structure and complex nonlinear mechanics has been attracting intensive attention over the past decades both in material science and tissue engineering. Polyisocyanopeptide (PIC) hydrogels are a class of fully synthetic materials that can mimic biogels, such as fibrin and collagen, in nearly all aspects, particularly the micron‐sized gel network and the strong strain‐stiffening behavior in the biological regime. Here, a biomimetic PIC/hydroxyapatite (HA) hybrid composite through an enzymatic biomineralization strategy is constructed. HA biominerals grew on PIC bundles in situ catalyzed by the embedded alkaline phosphatase (ALP), which further crosslinked the gel networks and reinforced the mechanical property of PIC hydrogels. Significantly, PIC/HA composites exhibited ultra‐responsive nonlinear mechanics with higher sensitivity to mechanical stress compared with those without biomineralization. As a consequence, the presence of HA can provide cell adhesion sites for PIC gels and induce osteogenic differentiation of pre‐osteoblasts by virtue of the changes in mechanical properties. With these outstanding properties, therefore, PIC/HA composites present promising prospects in bone tissue engineering as biomimetic ECM. [ABSTRACT FROM AUTHOR]

Maintaining quiescence of stem cells is a potential way to decrease cell nutrition demand for restoring the organization. Herein, a biomimetic peptide to maintain quiescence of stem cells through C-X-C motif chemokine ligand 8 (CXCL8)-C-X-C motif chemokine receptor 1 (CXCR1) pathway against intervertebral disc degeneration (IVDD) is developed. First, it is confirmed that quiescence can be induced via inhibiting phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in nucleus pulposus stem cells (NPSCs). Meanwhile, it is well known that CXCR1, a chemokine receptor, can be targeted by CXCL8, resulting in cell proliferation via activating PI3K/Akt/mTOR pathway. Second, a biomimetic peptide (OAFF) that can bind to CXCR1 and form fibrous networks on NPSCs, mimicking extracellular matrix formation is developed. The multivalent effect and long-term binding to CXCR1 on NPSCs of OAFF fibers offer forcefully competitive inhibition with natural CXCL8, which induces NPSCs quiescence and ultimately overcomes obstacle in intradiscal injection therapy. In rat caudal disc puncture model, OAFF nanofibers still maintain at 5 weeks after operation and inhibit degeneration process of intervertebral disc in terms of histopathology and imageology. In situ fibrillogenesis of biomimetic peptide on NPSCs provides promising stem cells for intradiscal injection therapy against IVDD., (© 2023 Wiley-VCH GmbH.)

Chitosan-poly(L-lactic acid-co-ε-caprolactone)(50:50) (P(LLA-CL)) (CS/P(LLA-CL)) blends were electrospun into nanofibers using 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and trifluoroacetic acid (TFA) as solvents. Chitosan, which is difficult to electrospin into nanofibers, could be easily electrospun into nanofibers with addition of a small portion of P(LLA-CL). The fiber diameter depended on both the polymer concentration and the blend ratio of chitosan to P(LLA-CL). The average fiber diameter increased with increasing polymer concentration and decreasing the blend ratio of chitosan to P(LLA-CL). X-ray diffractometry (XRD) and Fourier-transform infrared (FT-IR) spectra were measured to characterize blended nanofibers. The porosity of CS/P(LLA-CL) nanofiber mats increased with increasing the weight ratio of chitosan to P(LLA-CL), while both the tensile strength and the ultimate strain increased with increasing P(LLA-CL) ratio. Fibroblast cell growth on nanofiber mats were investigated with MTT assay and scanning electron microscope (SEM) observation. The highest cell proliferation was observed on the nanofiber mats when the weight ratio of chitosan to P(LLA-CL) was 1:2. As SEM images shown, fibroblast cells showed a polygonal shape on blend nanofiber mats and migrated into the nanofiber mats. [ABSTRACT FROM AUTHOR]

Traditional hydrogels often fail to match the dynamic interactions between mechanical and cellular behaviors exhibited by the natural cartilage extracellular matrix. In this research, we constructed a novel hybrid hydrogels system based on sodium alginate and polyglutamic acid. By controlling the grafting rate and concentration of polymer, the gelation time and mechanical strength can be adjusted between range of 8–28 s and 60–144 kPa. By adding microcrystalline cellulose into the system, so that the degradation time was prolonged (125%) and the swelling rate was reduced (470%). Additionally, the presence of hydrazone bonds gives the system some dynamic response characteristics, and the hydrogel exhibits excellent self healing and injectable ability. It was found that the system had positive cytocompatibility (80%), which accelerated regulatory gene expression in cartilage tissue. In conclusion, this injectable hydrogel with self-healing and customizable mechanical strength will have broad application prospects in future biomedical engineering. [Display omitted] • Adjustable the mechanical strength (60–144 kPa) and gelation time (8–28 s). • Micro-nano enhancement of hydrogel system using microcrystalline cellulose. • Simulating the construction chondrocytes of 3D dynamic microenvironment. • Promoting chondrogenic differentiation of stem cells. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation is a therapy for irreversible liver failure; however, at present, donor organs are in short supply. Cell transplantation therapy for liver failure is still at the developmental stage and is critically limited by a shortage of human primary hepatocytes., Aim: To investigate the possibility that hepatic progenitor cells (HPCs) prepared from the portal branch-ligated hepatic lobe may be used in regenerative medicine, we attempted to enable the implantation of extracellular matrices containing organoids consisting of HPC-derived hepatocytes and non-parenchymal cells., Methods: In vitro liver organoid tissue has been generated by accumulating collagen fibrils, fibroblasts, and HPCs on a mesh of polylactic acid fabric using a bioreactor; this was subsequently implanted into syngeneic wild-type mice., Results: The in vitro liver organoid tissues generated transplantable tissues in the condensed collagen fibril matrix and were obtained from the mouse through partial hepatectomy., Conclusion: Liver organoid tissue was produced from expanded HPCs using an originally designed bioreactor system. This tissue was comparable to liver lobules, and with fibroblasts embedded in the network collagen fibrils of this artificial tissue, it is useful for reconstructing the hepatic interstitial structure., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest relevant to this manuscript., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

The extracellular matrix (ECM) has not only cell-binding sites for cell attachment but also protein-binding sites for molecular sequestration. Aptamers have high binding affinities and specificities against their target molecules. Thus, the purpose of this work was to develop dual aptamer-functionalized hydrogels for simultaneously recapitulating the two key features of the ECM in binding cells and sequestering proteins. We synthesized the hydrogels using free-radical polymerization in a freezing procedure. As the hydrogels were macroporous with pores of 40-50 μm, both cells and proteins could be loaded into the hydrogels after the synthesis. Importantly, the vascular endothelial growth factor (VEGF) aptamer improved VEGF sequestration and reduced the apparent diffusivity of VEGF by over 2 orders of magnitude, resultantly prolonging VEGF retention and release. The c-MET aptamer promoted the attachment of endothelial cells in the hydrogel network. When two aptamers were both incorporated into the hydrogel, they could produce synergistic effects on cell survival and growth. Thus, this work has successfully demonstrated the potential of developing biomimetic ECMs with two key functions of cell attachment and protein sequestration using dual aptamer-functionalized hydrogels.

Acute spinal cord injury is a devastating injury that may lead to loss of independent function. Stem-cell therapies have shown promise; however, a clinically efficacious stem-cell therapy has yet to be developed. Functionally, endothelial progenitor cells induce angiogenesis, and neural stem cells induce neurogenesis. In this study, we explored using a multimodal therapy combining endothelial progenitor cells with neural stem cells encapsulated in a bioactive biomimetic hydrogel matrix to facilitate stem cell-induced neurogenesis and angiogenesis in a rat hemisection spinal cord injury model., Design: Laboratory experimentation., Setting: University laboratory., Subjects: Female Fischer 344 rats., Interventions: Three groups of rats: 1) control, 2) biomimetic hydrogel therapy, and 3) combined neural stem cell, endothelial progenitor cell, biomimetic hydrogel therapy underwent right-sided spinal cord hemisection at T9-T10. The blinded Basso, Beattie, and Bresnahan motor score was obtained weekly; after 4 weeks, observational histologic analysis of the injured spinal cords was completed., Measurements and Main Results: Blinded Basso, Beattie, and Bresnahan motor score of the hind limb revealed significantly improved motor function in rats treated with combined neural stem cell, endothelial progenitor cell, and biomimetic hydrogel therapy ( p < 0.05) compared with the control group. The acellular biomimetic hydrogel group did not demonstrate a significant improvement in motor function compared with the control group. Immunohistochemistry evaluation of the injured spinal cords demonstrated de novo neurogenesis and angiogenesis in the combined neural stem cell, endothelial progenitor cell, and biomimetic hydrogel therapy group, whereas, in the control group, a gap or scar was found in the injured spinal cord., Conclusions: This study demonstrates proof of concept that multimodal therapy with endothelial progenitor cells and neural stem cells combined with a bioactive biomimetic hydrogel can be used to induce de novo CNS tissue in an injured rat spinal cord., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.This work was performed at Duke University, Durham, NC., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

The development of biomaterials for application in advanced therapies requires thorough characterization of its biological behavior, which ultimately entails in vivo compatibility and performance assays. Electrospun fiber membranes of poly(l-lactic acid) (PLLA) and fish gelatin blends were produced and characterized, coupling the biomechanical features of PLLA with gelatin (GEL) biocompatibility. Fiber diameter was not affected by polymer blending, whereas the swelling degree increased with increasing GEL contents for values up to 566 ± 13%, behaving as a superhydrophilic material. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) adhesion was favored in the PLLA-GEL membranes, and cell viability was not affected after 7 days in culture. Membranes were then evaluated for in vivo biocompatibility through subcutaneous implantation in a rat model, for up to 15 days. No significant differences between the biological behavior of PLLA, PLLA-GEL, and GEL electrospun membranes at 15 days postimplantation were verified, with attained inflammation scores supporting an acceptable tissue response, deeming them fit for further biological assays. This work demonstrates that fiber blends of PLLA and GEL present promising in vitro and in vivo characteristics to be explored for tissue engineering.