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Biomaterials regulate macrophages and promote regeneration function, which is a new hot pot in tissue engineering and regenerative medicine. The research based on macrophage materials biology has appeared happy future, but related research on regulating macrophages and promoting tissue regeneration is still in its infancy. The surface roughness of...
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... as well as the following wound healing or fibrosis reactions [2]. Under different conditions, macrophages can be differently polarized, exhibit M1-(proinflammation) and M2-(tissue repair) phenotypes and secrete different cytokines and small molecules [3]. The schematic diagram of macrophages interactions in bone regeneration was shown in Fig. 1. It is known that the transition and balance between M1-and M2-phenotype are essential for tissue repair. The disorder of macrophage polarization and failure to restore M1 and M2 phenotypes to a normal balance may lead to the formation of foreign body giant cells, which is related to the failure of implant materials [4]. After ...
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Biomaterials used in tissue engineering and regenerative medicine applications benefit from longitudinal monitoring in a non-destructive manner. Label-free imaging based on fluorescence lifetime imaging (FLIm) and Raman spectroscopy were used to monitor the degree of genipin (GE) cross-linking of antigen-removed bovine pericardium (ARBP) at three i...
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... Previous study also found that the surface roughness of biomaterials could regulate macrophage polarization. On the rough surface of hydrogel, more macrophages exhibited M1 phenotype and high-level secretion of inflammatory factor (TNF-α and IL-6), while smoother surface induced M2 phenotype [50,51]. In addition, the form of the biomaterial also regulates the immune response. ...
Endogenous regeneration is becoming an increasingly important strategy for wound healing as it facilitates skin's own regenerative potential for self-healing, thereby avoiding the risks of immune rejection and exogenous infection. However, currently applied biomaterials for inducing endogenous skin regeneration are simplistic in their structure and function, lacking the ability to accurately mimic the intricate tissue structure and regulate the disordered microenvironment. Novel biomimetic biomaterials with precise structure, chemical composition, and biophysical properties offer a promising avenue for achieving perfect endogenous skin regeneration. Here, we outline the recent advances in biomimetic materials induced endogenous skin regeneration from the aspects of structural and functional mimicry, physiological process regulation, and biophysical property design. Furthermore, novel techniques including in situ reprograming, flexible electronic skin, artificial intelligence , single-cell sequencing, and spatial transcriptomics, which have potential to contribute to the development of biomimetic biomaterials are highlighted. Finally, the prospects and challenges of further research and application of biomimetic biomaterials are discussed. This review provides reference to address the clinical problems of rapid and high-quality skin regeneration.
... This can inadvertently prolong the dominance of M1 macrophages, potentially triggering a foreign body reaction [12]. As a result, alongside promoting tissue regeneration, remodulating macrophage polarization emerges as a vital strategy to manage the inflammatory response [13]. Various efforts have been made to manipulate the immune response by adjusting the scaffold's physical properties or by incorporating specific cytokines to induce a shift towards the M2 macrophage phenotype [14]. ...
Macrophage-mediated bone immune responses significantly influence the repair of bone defects when utilizing tissue-engineered scaffolds. Notably, the scaffolds' physical structure critically impacts macrophage polarization. The optimal pore size for facilitating bone repair remains a topic of debate due to the imprecision of traditional methods in controlling scaffold pore dimensions and spatial architecture. In this investigation, we utilized fused deposition modeling (FDM) technology to fabricate high-precision porous polycaprolactone (PCL) scaffolds, aiming to elucidate the impact of pore size on macrophage polarization. We assessed the scaffolds' mechanical attributes and biocompatibility. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression levels of macrophage-related genes, and enzyme linked immunosorbent assay (ELISA) for cytokine secretion levels. In vitro osteogenic capacity was determined through alkaline phosphatase (ALP) and alizarin red staining (ARS). Our findings indicated that macroporous scaffolds enhanced macrophage adhesion and drove their differentiation towards the M2 phenotype. This led to the increased production of anti-inflammatory factors and a reduction in pro-inflammatory agents, highlighting the scaffolds' immunomodulatory capabilities. Moreover, conditioned media from macrophages cultured on these macroporous scaffolds bolstered the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), exhibiting superior osteogenic differentiation potential. Consequently, FDM-fabricated PCL scaffolds, with precision-controlled pore sizes, present promising prospects as superior materials for bone tissue engineering, leveraging the regulation of macrophage polarization.
... Immunomodulatory biomaterials not only interact with macrophage cells but also elicit host-specific immunity (implant-mediated immune response) and regulating the fate of macrophages [4]. The surface topology (stiff or soft matrix) [5][6][7][8][9], chemical composition [10][11][12], particle size [10,13,14], porosity [15,16], self-assembly [17,18], wettability [19][20][21][22], and roughness [23,24] of the biomaterial promote the specific immune response. Moreover, the degradation products of biomaterials may exhibit various immunomodulatory effects on immune cells, which can initiate a local immune response at the implantation site [4]. ...
Macrophage-assisted immunomodulation is an alternative strategy in tissue engineering, wherein the interplay between pro-inflammatory and anti-inflammatory macrophage cells and body cells determines the fate of healing or inflammation. Although several reports have demonstrated that tissue regeneration depends on spatial and temporal regulation of the biophysical or biochemical microenvironment of the biomaterial, the underlying molecular mechanism behind immunomodulation is still under consideration for developing immunomodulatory scaffolds. Currently, most fabricated immunomodulatory platforms reported in the literature show regenerative capabilities of a particular tissue, for example, endogenous tissue (e.g., bone, muscle, heart, kidney, and lungs) or exogenous tissue (e.g., skin and eye). In this review, we briefly introduced the necessity of the 3D immunomodulatory scaffolds and nanomaterials, focusing on material properties and their interaction with macrophages for general readers. This review also provides a comprehensive summary of macrophage origin and taxonomy, their diverse functions, and various signal transduction pathways during biomaterial-macrophage interaction, which is particularly helpful for material scientists and clinicians for developing next-generation immunomodulatory scaffolds. From a clinical standpoint, we briefly discussed the role of 3D biomaterial scaffolds and/or nanomaterial composites for macrophage-assisted tissue engineering with a special focus on bone and associated tissues. Finally, a summary with expert opinion is presented to address the challenges and future necessity of 3D bioprinted immunomodulatory materials for tissue engineering.
... Adrenaline affects macrophage polarization regulated by MC via the PI3K/Akt signaling pathway [38]. The surface roughness and the nanostructure of MC regulates the polarization of macrophages [223]. On the rough surface, macrophages tend to polarize into the inflammatory M1 phenotype and secrete inflammatory factors (tumor necrosis factor-α and interleukin-6) at high levels. ...
... On the rough surface, macrophages tend to polarize into the inflammatory M1 phenotype and secrete inflammatory factors (tumor necrosis factor-α and interleukin-6) at high levels. While, on the smoother surface, macrophages induce polarization toward the M2 phenotype [223]. IMC and HIMC promote the polarization of M2 macrophages and increase the expression of M2-related anti-inflammatory cytokines IL-10 and arginase-1 at the cell, protein, and gene levels [31,88,221]. ...
Mineralized collagen (MC) is the basic unit of bone structure and function and is the main component of the extracellular matrix (ECM) in bone tissue. In the biomimetic method, MC with different nanostructures of neo-bone have been constructed. Among these, extra-fibrous MC has been approved by regulatory agencies and applied in clinical practice to play an active role in bone defect repair. However, in the complex microenvironment of bone defects, such as in blood supply disorders and infections, MC is unable to effectively perform its pro-osteogenic activities and needs to be functionalized to include osteogenesis and the enhancement of angiogenesis, anti-infection, and immunomodulation. This article aimed to discuss the preparation and biological performance of MC with different nanostructures in detail, and summarize its functionalization strategy. Then we describe the recent advances in the osteo-inductive properties and multifunctional coordination of MC. Finally, the latest research progress of functionalized biomimetic MC, along with the development challenges and future trends, are discussed. This paper provides a theoretical basis and advanced design philosophy for bone tissue engineering in different bone microenvironments.
... Inflammasome, in turn, triggers a pro-inflammatory signaling cascade of the innate immune system [119,120]. Cationic biomaterials are more likely to stimulate inflammatory responses than anionic or neutral biomaterials [121]. In contrast, Bartneck, et al. [119] demonstrated that positively Fig. 6. ...
Objectives:
The current standard for treating irreversibly damaged dental pulp is root canal therapy, which involves complete removal and debridement of the pulp space and filling with an inert biomaterial. A regenerative approach to treating diseased dental pulp may allow for complete healing of the native tooth structure and enhance the long-term outcome of once-necrotic teeth. The aim of this paper is, therefore, to highlight the current state of dental pulp tissue engineering and immunomodulatory biomaterials properties, identifying exciting opportunities for their synergy in developing next-generation biomaterials-driven technologies.
Methods:
An overview of the inflammatory process focusing on immune responses of the dental pulp, followed by periapical and periodontal tissue inflammation are elaborated. Then, the most recent advances in treating infection-induced inflammatory oral diseases, focusing on biocompatible materials with immunomodulatory properties are discussed. Of note, we highlight some of the most used modifications in biomaterials' surface, or content/drug incorporation focused on immunomodulation based on an extensive literature search over the last decade.
Results:
We provide the readers with a critical summary of recent advances in immunomodulation related to pulpal, periapical, and periodontal diseases while bringing light to tissue engineering strategies focusing on healing and regenerating multiple tissue types.
Significance:
Significant advances have been made in developing biomaterials that take advantage of the host's immune system to guide a specific regenerative outcome. Biomaterials that efficiently and predictably modulate cells in the dental pulp complex hold significant clinical promise for improving standards of care compared to endodontic root canal therapy.
... With an increasing understanding of the mechanisms underlying biomaterial-mediated skin wound healing, it is generally considered that immune cells within the wound bed have critical roles in orchestrating the healing process [11]. Particularly, macrophages are the main effector cells regulated by biomaterials to improve the healing process [12]. ...
Bioactive wound dressings that are capable of regulating the local wound microenvironment have attracted a very large interest in the field of regenerative medicine. Macrophages have many critical roles in normal wound healing, and the dysfunction of macrophages significantly contributes to impaired or non-healing skin wounds. Regulation of macrophage polarization towards an M2 phenotype provides a feasible strategy to enhance chronic wound healing, mainly by promoting the transition of chronic inflammation to the proliferation phase of wound healing, upregulating the level of anti-inflammatory cytokines around the wound area, and stimulating wound angiogenesis and re-epithelialization. Based on this, modulation of macrophage functions by the rational design of bioactive scaffolds has emerged as a promising way to accelerate delayed wound healing. This review outlines current strategies to regulate the response of macrophages using bioactive materials, with an emphasis on extracellular matrix-based scaffolds and nanofibrous composites.
... For the wound healing, M2 macrophages should replace the M1 macrophages (work in the initial stage) to promote tissue repair by releasing anti-inflammatory cytokines, which has inspired the development of an immunomodulatory hydrogel ( Figure 14) [450]. The "immune-interactive" biomaterials take advantage of many strategies, including adjusting the pore size, stiffness and 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 surface topography of biomaterials, to help the regeneration via regulating macrophages polarization [451,452]. Besides, the bioactive factors or ions released from biomaterials can also tune the ratio of M2/M1 macrophages [453,454]. ...
Nowadays, biomaterials have evolved from the inert supports or functional substitutes, to the bioactive materials able to trigger or promote the regenerative potential of tissues. The interdisciplinary progress has broadened the definition of “biomaterials”, and a typical new insight is the concept of tissue induction biomaterials. The term “regenerative biomaterials” and thus the contents of the present paper are relevant to yet beyond tissue induction biomaterials. This review summarizes the recent progress of medical materials including metals, ceramics, hydrogels, other polymers, and bio-derived materials. As the application aspects are concerned, this paper introduces regenerative biomaterials for bone and cartilage regeneration, cardiovascular repair, three dimensional bioprinting, wound healing, and medical cosmetology. Cell-biomaterial interactions are highlighted. Since the global pandemic of COVID-19, the review particularly mentions biomaterials for public health emergency. In the last section, perspectives are suggested: (1) Creation of new materials is the source of innovation; (2) Modification of existing materials is an effective strategy for performance improvement; (3) Biomaterial degradation and tissue regeneration are required to be harmonious with each other; (4) Host responses can significantly influence the clinical outcomes; (5) The long-term outcomes should be paid more attention to; (6) The non-invasive approaches for monitoring in vivo dynamic evolution are required to be developed; (7) Public health emergencies call for more research & development of biomaterials; (8) Clinical translation needs to be pushed forward in a full-chain way. In the future, more new insights are expected to be shed into the brilliant field — regenerative biomaterials.
... The surface roughness and hydrophilicity of biomaterials affect the polarization of macrophages. Li et al. (6) investigated the effects of mineralized collagen (MC) with different surface roughness on the macrophage polarization, and they found that MC with higher surface roughness tended to polarize macrophages to the M1 phenotype, whereas macrophages grown on smoother surfaces exhibited the M2 phenotype. Meanwhile, Hamlet et al. (7) compared the effect of hydrophilic titanium alloy surface on macrophage function and found that the more hydrophilic titanium alloy surface could reduce the expression of pro-inflammatory factors and promote the expression of anti-inflammatory factors in macrophages. ...
Ti-5Cu alloy has been proved to have excellent mechanical properties and cell compatibility and has certain antibacterial properties due to the addition of Cu. However, there are few studies on the effects of Ti-5Cu alloy on macrophage polarization and immune-related bone formation. In this study, we prepared Ti-5Cu alloy by three-dimensional printing technology and found that Ti-5Cu alloy presented a much smoother surface compared with Ti. In addition, the CCK-8 results indicated the Ti-5Cu alloy had no cytotoxicity to RAW264.7 cells by co-culture. The results of inductively coupled plasma mass spectrometry showed that the concentration of Cu²⁺ was 0.133 mg/L after 7 days of co-culture, and the CCK-8 results proved that Cu²⁺ had no cytotoxicity to RAW264.7 at this concentration. Then, we studied the effects of Ti-5Cu alloy on macrophage polarization; it was shown that the Ti-5Cu alloy is more prone to modulate the RAW264.7 polarization towards the M2 phenotype and the conditioned medium derived from Ti-5Cu alloy significantly promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells. However, when the expression of Oncostatin M (OSM) gene of RAW264.7 was knocked down, the osteogenic differentiation of MC3T3-E1 cells was decreased. This suggests that the OSM secreted by RAW264.7 co-cultured with Ti-5Cu alloy could accelerate the osteogenic differentiation of MC3T3-E1 cells by acting on OSMR/gp130 receptors.
... Depending on contextdependent polarization profiles, macrophage polarized to pro-inflammatory phenotype (M1 macrophage) or protissue regeneration (anti-inflammatory, M2 macrophage) phenotype (Badylak, 2016;Purnell and Hines, 2017;Eming et al., 2017). Therefore, the accurate and quickly conversion from M1 macrophage to M2 macrophage will contribute to positive bone reconstruction and be essential under the bone-forming environment regulating osteoblast differentiation (Brown and Badylak, 2013;Li et al., 2020;Xie et al., 2020). ...
... Mineralized collagen (MC) was fabricated bionic mineralization and displayed absolute merit in degradation fast in vitro, high hardness, and accelerating osteogenesis differentiation of hMSCs (Xu et al., 2016;Liu et al., 2017;Li et al., 2020;Meng et al., 2021). Shi et al. (2018) had proved that MC was more easily regulated macrophage M2 polarization than HA. ...
... From FESEM micrographs ( Figure 2B), many pores were distributed in the scaffolds with good interconnectivity. According to our previous cooperative research, the porosity of MC was about 70%, and the aperture size was 50-300 μm, which were incredibly similar to the natural bone in both composition and microstructure, and had excellent biocompatibility and biodegradable (Xu et al., 2016;Li et al., 2020). The hydrophilicity, shore hardness, and compression mechanics of MC scaffolds with different pore sizes were tested. ...
It is a new hot pot in tissue engineering and regenerative medicine to study the effects of physicochemical properties of implanted biomaterials on regulating macrophage polarization to promote bone regeneration. In this study, we designed and fabricated mineralized collagen (MC) with different microporous structures via in vitro biomimetic mineralization method. The microporous structures, mechanical properties, shore hardness and water contact angle measurements were tested. Live/dead cell staining, CCK-8 assay, phalloidine staining, staining of focal adhesions were used to detect cell behavior. ELISA, qRT-PCR, ALP, and alizarin red staining (ARS) were performed to appraise osteogenic differentiation and investigated macrophage response and their subsequent effects on the osteogenic differentiation. The results showed that RAW264.7 and MC3T3-E1 cells were able to survive on the MC. MC with the microporous structure of approximately 84 μm and 70%–80% porosity could promote M2 macrophage polarization and increase the expression level of TGF-β and VEGF. Moreover, the gene expression of the osteogenic markers ALP, COL-1, and OCN increased. Therefore, MC with different microporous structures mediated osteoimmunomodulation in bone regeneration. These data will provide a new idea of biomaterials inducing bone repair and direct the optimal design of novel immune biomaterials, development, and rational usage.
... The latest decade has witnessed rapid progress in biomaterials and medical devices, in both fundamental research [44][45][46][47][48][49][50][51] and applications [52][53][54][55][56][57][58][59]. While medical materials have been much developed [60][61][62][63][64][65][66][67][68], it is still challenging to find a biomaterialrelated cardiovascular device appropriate for interventional treatment. ...
The aortic dissection (AD) is a life-threatening disease. The transcatheter endovascular aortic repair (EVAR) affords a minimally invasive technique to save lives of these critical patients, and an appropriate stent-graft gets to be the key medical device during an EVAR procedure. Herein, we report a trilayer stent-graft and corresponding delivery system used for the treatment of the AD disease. The stent-graft is made of nitinol stents with an asymmetric Z-wave design and two expanded polytetrafluoroethylene (ePTFE) membranes. Each of inner and outer surfaces of the stent-graft was covered by an ePTFE membrane, and the two membranes were then sintered together. The biological studies of the sintered ePTFE membranes indicated that the stent-graft had excellent cytocompatibility and hemocompatibility in vitro. Both the stent-graft and the delivery system exhibited satisfactory mechanical properties and operability. The safety and efficacy of this stent-graft and the corresponding delivery system were demonstrated in vivo. In 9 canine experiments, the blood vessels of the animals implanted with the stent-grafts were of good patency, and there were no thrombus and obvious stenosis by angiography after implantation for 6 months. Furthermore, all of the 9 clinical cases experienced successful implantation using the stent-graft and its post-release delivery system, and the one-year follow-ups indicated the preliminary safety and efficacy of the trilayer stent-graft with an asymmetric Z-wave design for interventional treatment.
