Soft tissue integration is one major difficulty in the wide applications of metal materials in soft tissue-related areas. The inevitable inflammatory response and subsequent fibrous reaction toward the metal implant is one key response for metal implant-soft tissue integration. It is of great importance to modulate this inflammatory-fibrous response, which is mainly mediated by the multidirectional interaction between fibroblasts and macrophages. In this study, macrophages are induced to generate M1 and M2 macrophage immune microenvironments. Their cytokine profiles have been proven to have potentially multi-regulatory effects on fibroblasts. The multi-reparative effects of soft tissue cells (human gingival fibroblasts) cultured on metal material (titanium alloy disks) in M1 and M2 immune microenvironments are then dissected. Fibroblasts in the M1 immune microenvironment tend to aggravate the inflammatory response in a pro-inflammatory positive feedback loop, while M2 immune microenvironment enhances multiple functions of fibroblasts in soft tissue integration, including soft tissue regeneration, cell adhesion on materials, and contraction to immobilize soft tissue. Enlighted by the close interaction between macrophages and fibroblasts, we propose the concept of an “inflammatory-fibrous complex” to disclose possible methods of precisely and effectively modulating inflammatory and fibrous responses, thus advancing the development of metal soft tissue materials.

With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterials. Decellularized extracellular matrix (dECM) has been extensively used in the clinical treatment of tissue injury due to its favorable biocompatibility and similarity to the native tissue environment. However, most reported decellularization protocols may cause damage to the native structure of dECM, which undermines its inherent advantages and potential clinical applications. Here, we introduce a mechanically tunable dECM prepared by optimizing the freeze-thaw cycles. We demonstrated that the alteration in micromechanical properties of dECM resulting from the cyclic freeze-thaw process contributes to distinct macrophage-mediated host immune responses to the materials, which are recently recognized to play a pivotal role in determining the outcome of tissue regeneration. Our sequencing data further revealed that the immunomodulatory effect of dECM was induced via the mechnotrasduction pathways in macrophages. Next, we tested the dECM in a rat skin injury model and found an enhanced micromechanical property of dECM achieved with three freeze-thaw cycles significantly promoted the M2 polarization of macrophages, leading to superior wound healing. These findings suggest that the immunomodulatory property of dECM can be efficiently manipulated by tailoring its inherent micromechanical properties during the decellularization process. Therefore, our mechanics-immunomodulation-based strategy provides new insights into the development of advanced biomaterials for wound healing.

With the high incidence rate, distinctive implant characteristic and unique infection pattern, peri-implantitis (PI) requires a specially designed implant animal model for the researches on the pathogenesis and treatments. Previous small-animal PI models exhibit variability in implant site selection, design, and surgical procedures resulting in unnecessary tissue damage and less effectivity. Herein, a quantitative-analysis-based standardized rat model for transmucosal PI-related research was proposed. After dissecting the anatomic structures of the rat maxilla, we determined that placing the implant anterior to the molars in the rat maxilla streamlined the experimental period and enhanced animal welfare. We standardized the model by controlling the rat strain, gender, and size. The customized implant and a series of matched surgical instruments were appropriately designed. A clear, step-by-step surgical process was established. These designs ensured the success rate, stability, and replicability of the model. Each validation method confirmed the successful construction of the model. This study proposed a quantitative-analysis-based standardized transmucosal PI rat model with improved animal welfare and reliable procedures. This model could provide efficient in vivo insights to study the pathogenesis and treatments of PI and preliminary screening data for further large-animal and clinical trials.

This study aims to investigate the association between adenoid hypertrophy and facial development. A total of 388 children aged 1–13 years old who had undergone head MRI in Foshan Maternal and Child Health Hospital were collected, including 196 hypertrophic cases and 192 normal cases. The maxillofacial soft tissue indicators were measured and compared. The A/N ratio and adenoid thickness consistently increased with age in the hypertrophic group and the A/N ratio reached a maximum value three years earlier than the normal group. The pharyngeal airway space, vallecula of epiglottis to anterior plane distance of the third/fourth cervical vertebrae, angle of convexity, total angle of convexity, and the nasolabial angle in the hypertrophy group were smaller than those in the control group (p < 0.05). The thickness of adenoids, palate height, palate length, and tongue length in the hypertrophy group exceeded that of the control group (p < 0.05). To conclude, adenoid hypertrophy was associated with craniofacial features such as a convex facial profile, a narrowed nasopharyngeal airway, an elongated and heightened palate, a lengthened tongue or a lower tongue position. These findings emphasize the importance of early intervention for children with adenoid hypertrophy to mitigate potential adverse effects on maxillofacial development.

Biogenic hydroxyapatite is known for its osteoinductive potential due to its similarity to human bone and biocompatibility, but insufficient vascularization compared to autogenous bone during early implantation limits bone integration and osteogenesis. Fluorine has been shown to improve hydroxyapatite’s mechanical properties and the coupling of osteogenic and angiogenic cells. In this study, fluorine-modified biogenic hydroxyapatite (FPHA) with varying fluorine concentrations was prepared and tested for its ability to promote vascularized osteogenesis. FPHA prepared in this study retained the natural porous structure of biological cancellous bone and released F⁻ ions when immersed in cell culture medium. The extraction solutions of FPHA0.25 and FPHA0.50 promoted the formation of capillary-like tubes by human umbilical vein endothelial cells (HUVECs), with FPHA0.25 significantly upregulating vegf mRNA and VEGF protein levels in co-cultured human bone marrow mesenchymal stem cells (HBMSCs). Additionally, FPHA0.25 and FPHA0.50 upregulated pdgf-bb mRNA and PDGF-BB protein levels in HUVECs. In vivo experiments using a rabbit cranial defect model demonstrated that FPHA0.25 promoted early bone formation and angiogenesis in the defect area, enhanced VEGF secretion, and increased PDGFR-β expression in endothelial and mesenchymal cells. These findings suggest that fluorine-modified biogenic hydroxyapatite with an optimal fluorine concentration (FPHA0.25) may offer a promising strategy to enhance the body’s innate bone-healing potential by accelerating vascularization.

Metal implants holds significant promise for diverse fixed prostheses. However, their long-term reliability and broader application are hindered by challenges related to the disequilibrium at the soft-hard tissue interface. By using anti-inflammatory (PDA/IL4) and pro-inflammatory (PDA/LPS/IFNγ) coatings to modulate distinct immune characteristics, we discovered a dynamic bioactive structure at the soft-hard tissue interface around metal implant, which we have named the 'Remodeling Triangle Area' (RTA). We further demonstrate that the RTA can be influenced by the PDA/IL4 coating to favor a phenotype that enhances both innate and adaptive immunity. This leads to stronger epithelial adhesion, the formation of dense connective tissue via IGF1 secretion, and a more balanced soft-hard tissue interface through the OPG/RANKL axis. Conversely, the PDA/LPS/IFNγ coating shifts the RTA towards a phenotype that activates the innate immune response. This results in a less cohesive tissue structure and bone resorption, characterized by reduced IGF1 secretion and an imbalanced OPG/RANKL axis. Over all, our study introduces the novel concept termed the 'Remodeling Triangle Area' (RTA), an immune-rich anatomical region located at the nexus of the implant interface, epithelial, connective, and bone tissue, which becomes highly interactive post-implantation to modulate the soft-hard tissue interface equilibrium. We believe that an RTA-centric, immunomodulatory approach has the potential to revolutionize the design of next-generation metal implants, providing unparalleled soft-hard tissue interface equilibrium properties.