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[Objectives] Surgical sutures can provide sufficient tensile strength to hold the edges of a surgical incision together to promote healing. However, suture-induced foreign body reactions can exacerbate tissue inflammation depressing tissue healing. This study aimed to investigate variations in suture intensity and tissue inflammation after suturing the feline abdominal wall with different gauges of suture. [Methods] Feline abdominal skin and muscle were sutured using USP 2-0, 3-0, 4-0, 5-0 PGA sutures, and tissue suture intensity was assessed through uniaxial tensile testing in vitro. USP 2-0, 3-0, 4-0, 5-0 PGA sutures were implanted into feline abdominal muscles. After implantation, tissues were sampled at 1, 14 and 90 d. The expression levels of inflammatory factors were quantified using RT-qPCR and ELISA. The degree of inflammatory infiltration was evaluated in tissue sections. [Results]The results of skin and muscle suture intensity tests showed that the USP 5-0 PGA suture group experienced more suture breakage. Below 50% strain, there were no significant differences in stress among the groups (P>0.05) in vitro. At maximum tensile strength, there were no significant differences in strain, stress, and tensile strength among groups(P>0.05). At 1 and 14 d after suture implantation in vivo, the mRNA and protein expression levels of inflammatory factors (IL-1β, IL-6 and TNF-α)decreased with decreasing suture diameter, and the inflammatory response of the tissues around the large-diameter suture was more severe (P<0.05). [Conclusions] USP 5-0 PGA suture is sufficient for matching the tensile strength requirements of general cat abdominal wall surgical incisions. Moreover, smaller-diameter sutures can significantly reduce tissue inflammation from suture implantation. [ABSTRACT FROM AUTHOR]

BACKGROUND: The foreign body reaction induced by the implantation of biomaterials can lead to encapsulation in fibrous tissue, impede the interaction between the implant and host tissue, compromise implant functionality, and reduce its lifespan. OBJECTIVE: To focus on the development of regulatory strategies for foreign body reactions in biomaterials, including strategies based on surface modification of biomaterials, drug delivery and biomimetic surface modification and discuss the advantages and limitations of these methods. METHODS: The relevant articles published from January 2000 to March 2024 were searched on PubMed, Wiley, EBSCOhost, ScienceDirect, and Elsevier databases using search terms “biological materials, foreign body reaction, fibrosis, macrophage, myofibroblasts, inflammation, regulation, tissue repair.” Finally, 69 articles were included for further analysis. RESULTS AND CONCLUSION: By modifying the surface characteristics of biomaterials, such as size, shape, roughness, surface charge, hydrophilicity, and mechanical stiffness, it is possible to mitigate immune system stimulation and reduce the risk of foreign body reaction. Controlled drug stimulation combined with controlled degradation of carrier materials can generate sustained chemical reactions that effectively minimize foreign body reaction. Biomimetic surface modification techniques like zwitterion coating, protein molecular coating, and other bioactive molecular coatings have been shown to significantly decrease short-term foreign body reaction. Due to the complexity of the immune response to implants and tissue regeneration, the overall balance between foreign body reaction and tissue regeneration should also be considered when designing and manufacturing implants. [ABSTRACT FROM AUTHOR]

BACKGROUND: The foreign body reaction induced by implanted biomaterials leads to the formation of surface fibrosis (also known as implant fibrosis), that is, biomaterials are wrapped by fibrous tissue, making them lose their functionality and producing serious clinical complications, which is a major problem in the field of tissue regeneration and repair. The key cells involved in implant fibrosis are macrophages. However, the effects and mechanism of macrophages on the process of implant fibrosis and the strategy of inhibiting fibrosis remain unclear. OBJECTIVE: To review the effects of macrophage polarization and differentiation events on material fibrosis, including fibrogenic signal pathways, and strategies to inhibit biomaterial fibrosis based on specific regulation of macrophages. METHODS: The relevant articles up to 2022 were searched on PubMed, Wiley, EBSCOhost, ScienceDirect, and Elsevier databases using English search terms “macrophages, biological materials, fibrosis, foreign body reaction, myofibroblasts, inflammation, regulation, surface topology, mechanical properties, chemical signals”, and 60 articles were finally included for the further analysis. RESULTS AND CONCLUSION: (1) Both M1 and M2 macrophages may participate in the formation of biomaterial fibrosis. Maybe strategies that regulate macrophage polarity alone cannot inhibit the formation of fibrosis in biomaterials. (2) As a key cellular event in the regulation of macrophage-mediated biomaterial fibrosis, the differentiation of macrophages into myofibroblasts can induce the expression of marker α-smooth muscle actin, indicating that this process has a direct effect on fibrosis. (3) In terms of the signaling pathway of macrophages promoting fibrosis, the analysis suggests that there may be differences in the signaling pathway of macrophages with different phenotypes. (4) Two main pathways are involved in the regulation of macrophage-induced inflammation using the physical properties of biomaterials. First, based on the biomaterial surface topology, the construction of patterning surface less than 100 nm or the enhancement of surface roughness of biomaterial is expected to reduce macrophage fusion and expression of inflammatory factors, reducing fibrosis caused by macrophages. Second, researchers prefer to design and prepare biomaterials with smaller modulus of elasticity to reduce the stress transfer induced by the implant to the injured tissue, reduce macrophage-induced inflammation, and improve the fibrosis during tissue repair. (5) Regarding the use of chemical signals to regulate the expression of macrophage-induced inflammation, regulatory strategies can be implemented mainly in macrophage-derived inflammatory factors, as well as chemical signals for macrophage recruitment, fusion, and differentiation; therefore, effective use of inhibitors and antioxidants can achieve reverse regulation of transforming growth factor β1, reactive oxygen species, nuclear transcription factor κB, and miRNA-21 through the above pathways, thus delaying fibrosis induced by macrophages. [ABSTRACT FROM AUTHOR]

With the advances in understanding the relationships among biomaterials, the immune system and the skeletal system, the host responses elicited by implanted biomaterials can be balanced by properly designing material characteristics from the perspective of osteoimmunology. The immunoregulatory properties of bone tissue engineering scaffolds provide advantages for inducing macrophages from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype and promoting osseointegration. Hydrogels are increasingly a focus in bone tissue engineering, and the immune response can be affected by different compositions of hydrogels, such as the sources, concentration, molecular weight, coupling with fibronectin, and the addition of cross-linking agents. Different physicochemical properties of modified hydrogels can trigger different host immune responses, modified by using soft photolithography to fabricate micropatterned hydrogels, adding enzyme-sensitive sequences, ester bonds and dynamic covalent chemistry to prevent rapid or slow degradation of the hydrogels, and adding porogens and 3D printing to modify the hydrogels with macroporous interconnective pore structures, soft and injectable hydrogels, etc. These optimized hydrogels can reduce proinflammatory factors, promote M2 macrophage polarization, and minimize foreign body reactions to evoke bone regeneration. However, the mechanism underlying the bone immune response is still poorly understood, and further study of the effects of hydrogels with different physicochemical properties on immune regulation is needed.

BACKGROUND: In recent years, the way of repairing tissue defects with biological scaffolds has been widely concerned by scholars. As an external implant, the body inflammatory response is vital for the integration between materials and tissues, in which macrophages serve as important participants and regulators. It is necessary to understand the interaction between biological scaffolds and macrophages, which will have crucial guiding significance for the design of new scaffolds in the future. OBJECTIVE: To review the researches on the interaction between biological scaffolds and macrophages as well as the regulation of this dynamic balance between them. METHODS: PubMed, Web of Science, and CNKI were used to search the related articles published from 1971 to 2021. The search terms were “macrophage polarization, M2, foreign body, tissue engineering, scaffolds, mediation, bone, degradation” in English and Chinese. An inductive analysis was conducted in the 76 selected articles on the latest research progress in this field. RESULTS AND CONCLUSION: (1) Immune response plays an indispensable role in tissue regeneration and repair. (2) Macrophage is an important regulator of inflammatory response. It will polarize into different phenotypes such as pro-inflammatory or anti-inflammatory according to different microenvironment stimuli. On one hand, the imbalance of macrophage polarization in different stages of inflammatory response will hinder the integration of biological scaffold materials and tissue repair. The high expression of pro-inflammatory macrophages in the early stage of biomaterial implantation is conducive to the integration of biomaterials. In the late stage of inflammation, however, the sustained high expression of pro-inflammatory macrophages will hinder the formation of new bone. On the other hand, the properties of biological scaffolds (composition, hardness, roughness, surface geometry, hydrophilicity, etc.) will affect the polarization direction of macrophages. For example, adjusting the surface morphology of scaffolds cannot change the ideal physical and chemical properties of scaffolds, but promote effectively the polarization of macrophages towards pro-regenerative phenotype and tissue repair. (3) At present, the effect of biological scaffolds on macrophages has been realized by changing the composition, preparation methods and adjusting the physical and chemical properties of scaffolds. However, how to efficiently regulate this dynamic balance is still the focus and our key direction in the future, In particular, how to successfully translate the ideal results of basic research in vitro into practical application in vivo is still under further exploration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Poly(L-lactic acid) (PLLA) microparticle (Sculptra®) has been approved by FDA as the dermal filler to regenerate collagen for anti-aging purpose. Because of its irregular particle shape, it is prone to excessive inflammation. OBJECTIVE: To investigate the effects of irradiation on the molecular weight, size and morphology of the poly(L-lactic acid) microspheres, as well as the foreign body reaction and the neocollagenesis stimulation of the poly(L-lactic acid) microspheres dermal filler implanted subcutaneously into back of rabbits. METHODS: Microspheres were prepared by the emulsion-solvent evaporation method and utilized as the dermal filler with the same Sculptra’®s formula. The filler was sterilized by irradiation at 25 and 50 kGy, separately and the molecular weight, size and morphology of the microspheres were analyzed. The MTT assay was used to detect the effects of the microspheres at different concentrations (50, 100, 250, and 500 mg/L calculated by the concentration of microspheres) on the proliferation of mouse fibroblasts. The 25 kGy irradiated dermal filler (experimental group) and saline (control group) were injected into the back of the rabbit subcutaneously. Hematoxylin-eosin staining, Masson staining, and immunofluorescence staining of CD68, type I collagen and type III collagen were performed on the back tissue of the injection site at the set time points. RESULTS AND CONCLUSION: (1) With the increase of the radiation dose, the viscosity, viscosity-average molecular weight and number-average molecular weight of the microspheres decreased significantly, but the irradiation sterilization did not cause significant changes in the particle size and morphology of the microspheres. (2) MTT assay results demonstrated that when the mass concentration of the filler was lower than 250 mg/L, the cell survival rate was all >90%. Even when the material mass concentration reached the highest level 500 mg/L, the cell survival rate was still higher than 80%. Incubation for 72 hours also did not produce significant cytotoxicity. (3) In animal experiments, hematoxylin-eosin staining and CD68 immunofluorescence staining revealed that the filler caused slight inflammatory response from 0.5 to 4 months after implantation, and the inflammatory response reached the highest level at 6 months after implantation. Some microspheres were degraded to irregular shape or with pores on the surface, and the microspheres were degraded completely at 9 months after implantation. (4) In animal experiments, Masson staining and immunofluorescence staining of type I collagen and type III collagen exhibited that at 4 months after implantation, type I collagen was mainly around the microspheres, and type III collagen was mainly at the periphery. At 6 months after implantation, type I collagen near the microspheres increased, and type III collagen at the periphery increased. At 9 months after implantation, the fibrous encapsulation was mainly composed of type I collagen, and the ratio of type I collagen to type III collagen was close to the same at the periphery. (5) The results indicate that injectable poly(L-lactic acid) microsphere filler can stimulate collagen regeneration and can also reduce the degree of inflammatory response. [ABSTRACT FROM AUTHOR]

BACKGROUND: Foreign body reactions will lead to the failure of material implantation. In recent years, research on immunity has gradually become a hot spot. It is of great significance to select scaffold materials with good immune properties for the development of bone defect repair. OBJECTIVE: To investigate the effects of calcinated antler cancellous bone and untreated antler bone on the biological behavior of bone marrow-derived M1 macrophages. METHODS: Calcinated antler cancellous bone was prepared by physical and chemical methods. The physical and chemical properties of calcinated antler cancellous bone and untreated antler bone were detected by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. The extracts of calcinated antler cancellous bone and untreated antler bone were prepared and the contents of Ca, P and Mg in the extracts were determined. Bone marrowderived macrophages were cultured in vitro and polarized into M1 macrophages under lipopolysaccharide and interferon γ stimulation. These cells were then co-cultured with different extracts in calcinated antler cancellous bone and untreated antler bone groups, while co-cultured with an IMDM medium in control group, followed by cell counting kit-8 detection of cell survival, flow cytometry detection of M1 markers, and qPCR detection of macrophage-related genes. RESULTS AND CONCLUSION: (1) The contents of Ca, P and Mg were higher in the calcinated antler cancellous bone group than the untreated antler bone group. (2) The main functional groups in these two groups included OH-, PO4 3-, and CO3 2 -. (3) There was no significant difference in cell survival rate among the three groups for 1, 3, and 7 days of co-culture. (4) The expression rate of CD16/32 was lower in the calcinated antler cancellous bone group than the control group after 1-day co-culture. (5) The expression levels of pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-6 were lower in the calcinated antler cancellous bone group than the control group after 1 and 3 days of co-culture, while there was no significant difference between the untreated antler bone group and the control group. The expression of CD206, a main marker of M2 macrophages, was significantly higher in the calcinated antler cancellous bone group than the control group at 3 days of co-culture, while there was no significant difference between the untreated antler bone group and the control group at 1 and 3 days of co-culture. (6) To conclude, calcinated antler cancellous bone powder extract can reduce the expression of pro-inflammatory cytokines in M1 macrophages and promote their polarization to M2 macrophages [ABSTRACT FROM AUTHOR]

BACKGROUND: Bone tissue engineering is an effective bone defect repair program. Macrophages play an extremely important role in the immune response after implantation of tissue engineering materials. Interfering with its different polarization states has become a key means to regulate the local immune microenvironment. OBJECTIVE: To summarize the important role of macrophages in the immune response after biomaterial implantation and the research progress in promoting osteogenesis by regulating the polarization of macrophages in bone tissue engineering. METHODS: PubMed, Web of Science and CNKI were used to search the related articles published from 2016 to 2020. The retrieval article types were original research works and reviews. The search terms were “macrophage polarization, M2, scaffold, tissue engineering, foreign body response, implant, surface, bone” in English, and “macrophage polarization, M2, tissue engineering, foreign body response, implant, surface, bone” in Chinese. An inductive analysis was conducted in the selected articles on the latest research progress in this field. RESULTS AND CONCLUSION: The immune response plays an important role in tissue engineering and the regulation of the immune microenvironment is a key means of promoting osteogenesis in tissue engineered bone. The method of altering the physicochemical properties of the material, such as hydrophobicity, roughness and surface morphology has good stability for a long duration, achieves significant osteogenic improvements. Delivery of drugs, cytokines or bioactive ions has also worked well, but suffers from short release time and susceptibility to denaturation. Another strategy is regulation by engineered cellmacrophage crosstalk, where mesenchymal stem cells are highly immunomodulatory and can achieve immune modulation and bone repair promotion. The new study highlights the important role of exosomes to achieve controllable modulation of macrophage polarization and immune environment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Biomedical implants have been widely used in various orthopedic treatments. However, the existing bone implants often have the disadvantages of poor mechanical properties, immune response, microbial infection, poor healing and so on. Different surface modification techniques can effectively make up for these shortcomings. OBJECTIVE: To summarize the surface modification techniques of the current bone tissue engineering implants. METHODS: The first author searched the PubMed, CNKI, and VIP datadase to retrieve the article regarding repair of tuberculous bone defect published during 2000-2009 with the search terms "'bone tissue engineering; bone implant; surface modification; coating" in Chinese and English, respectively. The articles published recently or in high-impact journals were included in this study. RESULTS AND CONCLUSION: The surface of bone tissue engineering implants was modified by inorganic and organic components or by changing the surface topography of the implants. This improves the osteogenesis, bone conductivity, bacteriostasis，and biocompatibilily of bone implant to different degrees. However, we, need to solve some problems before this new implant is applied to the clinic: how to determine the optimal concentration of different surface modification componets, maximize bone healing, inhibit bacterial activity, and avoid other adverse reactions; how to avoid foreign body reaction and immune response caused by particles generatedby surface abrasion of these bone tissue engineering implants over time; how to incorporate various growth factors, proteins and other biological molecules into the coating without damaging their respective chemical structures and functions; how to guide the release of growth factors and molecules in a coordinated and controllable way. [ABSTRACT FROM AUTHOR]

BACKGROUND: α-n-Butyl cyanoacrylate medical adhesive (504 medical adhesive) has good biocompatibility and anti-bacterial properties. It is a simple and effective medical adhesive. Little is reported on the application of α-n-butyl cyanoacrylate medical adhesive in surgical incision closure in the field of oral cavity. OBJECTIVE: To investigate the effect of α-n-butyl cyanoacrylate medical adhesive on oral mucosal wounds healing. METHODS: Fifteen female SD rat (Laboratory Animal Center of Chongqing Medical University, China) models of oral mucosal incisions were established and then divided into a natural healing group (without any treatment), silk suture group (interrupted stitches with absorbable surgical suture), and 504 medical adhesive group (wound closure with α-n-butyl cyanoacrylate medical adhesive) group. At 7 days after surgery, gross and histological observation was performed. Twenty female SD rats were established into models of 1 cm x 1 cm oral mucosa defect and then divided into two groups: a natural healing group (without any treatment) and a 504 closure group (covering the wound defect with α-n-butyl cyanoacrylate medical adhesive). At 10 days after surgery, gross and histological observation of defect area was performed. This study was approved by the Animal Ethics Committee of Chongqing Medical University, China. RESULTS AND CONCLUSION: Oral mucosal incision wound model: gross observation showed that the wounds in the three groups healed well, and no inflammatory reaction such as swelling and pus was found. Histological observation showed that the epithelium of the silk suture group was complete and continuous, the nail process of the epithelium was short and flat, the number of fibroblasts in the lamina propria increased, and a large number of inflammatory cells infiltrated in the suture track area. In the natural healing and 504 closure groups, the mucosal epithelium healed well, the nail process of the epithelium was thin and long, the fibroblasts in the lamina propria proliferated actively, and there were many collagen fibers. The fibers in the 504 closure group were arranged more closely and orderly than those in the silk suture group. Oral mucosa defect model: Gross observation showed that the wound in the natural healing group did not heal completely, and there was no infection such as swelling, necrosis, and ulceration. In the 504 closure group, wound surface basically healed. Histological observation revealed that in the natural healing group, mucosal defect was obvious, the epithelial layer was not closely connected with the lamina propria, necrotic tissue, a small amount of fibroblasts and a large number of inflammatory cells were observed. In the 504 closure group, the length of margin of mucosal defect was significantly reduced, fibroblast proliferation and vascular regeneration could be observed in the lamina propria, and fibers were orderly arranged. These results suggest that α-n-butyl cyanoacrylate medical adhesive has little foreign body reaction and can promote the regeneration of mucosal tissue, providing a potential method to close oral mucosal wound. [ABSTRACT FROM AUTHOR]

Foreign body reactions induced by macrophages often cause delay or failure of wound healing in the application of tissue engineering scaffolds. This study explores the application of nanosilver (NAg) to reduce foreign body reactions during scaffold transplantation. An NAg hybrid collagen-chitosan scaffold (NAg-CCS) was prepared using the freeze-drying method. The NAg-CCS was implanted on the back of rats to evaluate the effects on foreign body reactions. Skin tissue samples were collected for histological and immunological evaluation at variable intervals. Miniature pigs were used to assess the effects of NAg on skin wound healing. The wounds were photographed, and tissue samples were collected for molecular biological analysis at different time points post-transplantation. NAg-CCS has a porous structure and the results showed that it could release NAg constantly for two weeks. The NAg-CCS group rarely developed a foreign body reaction, while the blank-CCS group showed granulomas or necrosis in the subcutaneous grafting experiment. Both matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were reduced significantly in the NAg-CCS group. The NAg-CCS group had higher interleukin (IL)-10 and lower IL-6 than the blank CCS group. In the wound healing study, M1 macrophage activation and inflammatory-related proteins (inducible nitric oxide synthase (iNOS), IL-6, and interferon-‍γ (IFN-‍γ)) were inhibited by NAg. In contrast, M2 macrophage activation and proinflammatory proteins (arginase-1, major histocompatibility complex-II (MHC-II), and found in inflammatory zone-1 (FIZZ-1)) were promoted, and this was responsible for suppressing the foreign body responses and accelerating wound healing. In conclusion, dermal scaffolds containing NAg suppressed the foreign body reaction by regulating macrophages and the expression of inflammatory cytokines, thereby promoting wound healing.