The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. Inspired by the acidic ...microenvironment at acute injury sites, a functional pH-responsive immunoregulation-assisted neural regeneration strategy was constructed. With the capability of directly responding to the acidic microenvironment at focal areas followed by triggered release of the IL-4 plasmid-loaded liposomes within a few hours to suppress the release of inflammatory cytokines and promote neural differentiation of mesenchymal stem cells in vitro, the microenvironment-responsive immunoregulatory electrospun fibers were implanted into acute spinal cord injury rats. Together with sustained release of nerve growth factor (NGF) achieved by microsol core-shell structure, the immunological fiber scaffolds were revealed to bring significantly shifted immune cells subtype to down-regulate the acute inflammation response, reduce scar tissue formation, promote angiogenesis as well as neural differentiation at the injury site, and enhance functional recovery in vivo. Overall, this strategy provided a delivery system through microenvironment-responsive immunological regulation effect so as to break through the current dilemma from the contradiction between immune response and nerve regeneration, providing an alternative for the treatment of acute spinal cord injury.
In recent decades, collagen is one of the most versatile biomaterials used in biomedical applications, mostly due to its biomimetic and structural composition in the extracellular matrix (ECM). ...Several attempts are proposed for designing innovative collagen‐based biomaterials and applying them in tissue regeneration. The regeneration of different tissues is prompted by different types and diverse physical forms of collagen‐based biomaterials prepared by various methods. Based on such concepts, the source, structure, and classification of collagen are briefly introduced in this review. Here, the commonly used physical forms and modification methods of collagen‐based biomaterials are reviewed, including hydrogels, scaffolds, and microspheres, followed by their applications in the regeneration of tissues and organs. Important proof‐of‐concept examples are described to demonstrate the outcomes on material characteristics, cellular reactions, and tissue regeneration. A concise assessment of the limitations that still exist and the developing trends in the future of collagen‐based biomaterials are put forward.
In this review, an overview of the different physical forms of collagen‐based biomaterials is provided and the corresponding commonly used fabrication methods as well as advanced technologies in detail followed by examples of their applications in the regeneration of tissues and organs are discussed. The limitations and potential development directions are also listed at the end.
Immune response and new tissue formation are important aspects of tissue repair. However, only a single aspect is generally considered in previous biomedical interventions, and the synergistic effect ...is unclear. Here, a dual-effect coating with immobilized immunomodulatory metal ions (e.g., Zn
) and osteoinductive growth factors (e.g., BMP-2 peptide) is designed via mussel adhesion-mediated ion coordination and molecular clicking strategy. Compared to the bare TiO
group, Zn
can increase M2 macrophage recruitment by up to 92.5% in vivo and upregulate the expression of M2 cytokine IL-10 by 84.5%; while the dual-effect of Zn
and BMP-2 peptide can increase M2 macrophages recruitment by up to 124.7% in vivo and upregulate the expression of M2 cytokine IL-10 by 171%. These benefits eventually significantly enhance bone-implant mechanical fixation (203.3 N) and new bone ingrowth (82.1%) compared to the bare TiO
(98.6 N and 45.1%, respectively). Taken together, the dual-effect coating can be utilized to synergistically modulate the osteoimmune microenvironment at the bone-implant interface, enhancing bone regeneration for successful implantation.
•Marine-based collagen as a resealable replacement for mammal-based collagen.•Potential advantages of MC thanks to its amenable chemical properties.•Methods for preparation of collagen from different ...marine sources.•Multiple possible combinations and applications of MC with a particular focus on drug delivery.
Tissues rely on collagen for structural and biological integrity, as well as for function and strength. Several collagen sources have been investigated due to its wide variety of applications, such as collagen from cows and pigs. However, mammalian-based collagen has been limited by diseases like bovine spongiform encephalopathy (BSE) and other religious limitations. Hence, fish collagen has caught the attention of the research community because it is easy to extract, has a high level of collagen content, excellent absorption properties, a low molecular weight, biocompatibility, little risk of disease transmission from animals to humans, negligible environmental contamination, and fewer ethical and religious concerns, posing as an ideal resource for product development. This review focuses on the growing role of marine collagen in the advances of various biomedical applications, such as drug delivery, tissue engineering, regeneration, and wound healing, which will be covered in depth.
Macrophage immunotherapy is an emerging treatment strategy that modulates the immune system to promote wound healing. The functionality and regeneration of tissue depend on spatially and temporally ...regulating the biophysical and biochemical microenvironmental with poorly understood mechanisms. Biomaterials are carefully crafted to display and deliver macrophage regulatory signals in a precise and near‐physiological way, serving as powerful artificial microenvironments in which to explore and direct the fate of macrophages. The review starts with discussing the classification and function of macrophages, and then introduces the polarization of macrophages in different microenvironments of conventional wounds and chronic wounds. Recent advances in biomaterials that balance the phenotypes of macrophages in wound healing are emphasized. Finally, looking ahead, the potential ability of biomaterial scaffolds to modulate immune signaling to produce an environment conducive to regeneration is discussed.
This review begins with a discussion of macrophages and the polarization of macrophages in the different microenvironments of conventional and chronic wounds. Then, recent advances in biomaterials that balance the macrophage phenotype in wound healing are highlighted. Finally, looking ahead, the potential ability of biomaterial scaffolds to modulate immune signaling to produce an environment conducive to regeneration is discussed.
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.
A microfluidics‐assisted strategy for entrapping bone marrow‐derived mesenchymal stem cells (BMSCs) and growth factors in photocrosslinkable gelatin microspheres which can sustain BMSC viability, support cell spreading inside the microspheres and migration to the microsphere surface, and enhance osteogenesis both in vitro and in vivo, is presented. The proposed approach can be utilized to facilitate bone regeneration with minimum invasiveness.
•Bio-inks for tissue-specific physicochemical microenvironments.•Combination of zone-specific bioinks and programmed printing paths.•Multichannel extrusion bioprinting technique for reconstructing ...tissues with anisotropic structure.•External stimulation during bioprinting for regulating cell behaviors.
Human tissue consists of various tissue-specific cells, extracellular matrix components and microstructures, and growth factors. With promising multi-cell and multi-material integration manufacturing feature, 3D extrusion bioprinting has shown outstanding application potential in the field of regenerative medicine. For functional tissue regeneration, bioprinted constructs not only play the role of a cell-delivery system, but also serve as an important host niche for cell proliferation and work. In order to meet the specific requirements of different tissue regeneration, development of bio-inks that provide tissue-specific biophysical cues and biochemical microenvironments is an important research topic. Furthermore, reconstruction of tissues with anisotropic structure, such as articular cartilage and meniscus, largely depend on the design of 3D bioprinting path for accurate arrangement of specific bio-inks. This review summarizes the advanced designs of tissue-specific 3D bioprinting of cell-laden constructs for functional regeneration of skeletal and locomotor systems such as bone, cartilage, skeletal muscle, and blood vessels via the collaboration of bio-ink and printing processes. It may provide a basis for synergistic design for functional regenerative constructs bioprinting in the future.
Protein is the key composition of all tissues, which has also been widely used in tissue engineering due to its superior biocompatibility and low immunogenicity. However, natural protein usually ...lacks active functions such as vascularization, osteo‐induction, and neural differentiation, which limits its further applications as a functional biomaterial. Here, based on the mimetic extracellular matrix feature of bovine serum albumin, injectable polypeptide‐protein hydrogels with vascularization and antibacterial abilities are constructed successfully via coordinative cross‐linking of sulfydryl groups with silver ions (Ag+) for the regeneration of infected wound. In this protein hydrogel system, (Ag+), acting as crosslinkers, can not only provide a sterile microenvironment and a strong and robust antibacterial ability but also introduce K2(SL)6K2 (KK) polypeptide, which endows the hydrogel with vascularization behavior. Furthermore, the in vivo data show that the polypeptide‐protein hydrogel has a considerable collagen deposition and vascularization abilities in the early stage of wound healing, resulting in rapid new tissue regeneration featured with newly appeared hair follicles. Altogether, this newly developed multifunctional 3D polypeptide‐protein hydrogel with vascularization, antibacterial properties, and hair follicle promotion can be a promising approach in biomedical fields such as infected wound healing.
Polypeptide‐protein hydrogels are designed and developed for promoting infected wound healing. Through coordinative cross‐linking of thiolated bovine serum albumin protein and thiolated vascular polypeptide with silver ions, the gels obtain additional vascularization and antibacterial activities that can accelerate infected wound healing. The hydrogel is highly promising as a novel protein‐based biomaterial for biomedical applications.
The periosteum plays a vital role in both development and injury healing process of bone. However, few researches have focused on artificial periosteum, which was also limited by the complexity on ...its construction and biological risks for clinical practice. In order to tackle this issue, inspired by the structural development of periosteum, we put forward a hierarchical micro/nanofibrous bionic periosteum with sustained releasing of VEGF as exogenous vascularized fibrous layer of periosteum to induce endogenous cambium layer in vivo for complete regeneration of periosteal and bone tissue, through collagen self-assembly and micro-sol electrospinning technologies. The VEGF encapsulated in hyaluronan-PLLA core-shell structure was demonstrated to be released in a durable way for angiogenesis in fibrous layer and bone defect area. Meanwhile, the self-assembly of collagen together with electrospun fibers contributed to a hierarchical micro/nanostructure which greatly mimicked the microenvironment of extracellular matrix to provide structural and biochemical cues for cell adhesion, proliferation and differentiation, and lead to the formation of cambium layer which mimicked the in-situ ossification manner as intramembranous ossification. As the motif of this study, the periosteal regeneration was characterized both by osteoblasts and periostin, which represented structural and molecular mechanisms respectively. Furthermore, the periosteal biomaterial proposed here possessed the superior abilities of scar inhibition, angiogenesis, osteogenesis to repair the bone defect in a uniform and rapid manner by inherent periosteal ossific mechanism involved in both intramembranous and endochondral ossification. Thus, the endogenous-exogenous combined bionic periosteum proved to be efficient and versatile in triggering periosteal and bone regeneration and hopefully supply a promising strategy for solving clinical issue.
Inspired by the structural development of periosteum, we put forward a hierarchical micro/nanofibrous bionic periosteum with sustained releasing of VEGF as exogenous vascularized fibrous layer of periosteum to induce endogenous cambium layer in vivo for complete periosteal and bone regeneration through collagen self-assembly and micro-sol electrospinning technologies. Display omitted
This review provides an overview of biologically modified nanoparticles as theranostic bionanomaterials, which are anticipated to revolutionize the current theranostic modalities of diseases in the ...clinic and exhibit huge potential for further clinical applications.
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Inspired by natural biology, cell membrane-mimetic surface engineering and cell membrane camouflaging technology have been widely investigated. Notably, the cell membrane-camouflaged nanoparticles (CM-NPs), which are produced by fusing synthetic nanoparticles with cellular membranes, gain unprecedented attention in biomedical fields. Compared with conventional nanosystems, these biomimetic nanoparticles (NPs) are bestowed with favored properties of elongated circulation time, immune evading and active targeting, which exhibit great potential in numerous biomedical applications and are anticipated to revolutionize the traditional nanomedicine. So far, a variety of cell membranes, along with expansive options of core materials, have been extensively investigated to construct the biomimetic system with unique functionalities. This review describes the evolution process from cell membrane-mimetic surface engineering to cell membrane camouflaging technology, which focuses on (I) cell membrane-mimetic surface engineering strategies (II) the fabrication of CM-NPs, (III) cell membrane-camouflaged nano-carriers, (VI) cell membrane camouflaged nano-phototherapeutic agents, (V) cell membrane camouflaged nano-antidotes, (VI) cell membrane camouflaged nanovaccines, (VII) cell membrane camouflaged nanoprobes, and (VIII) other relevant applications, providing an overview of the latest progress in the fabrication and application of cell membrane-based biomimetic and highlighting the major challenges as well as opportunities in this field.
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