A Standardized Rat Model to Study Peri-implantitis of Transmucosal Osseointegrated Implants.

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.

Balance between the CMC/ACP Nanocomplex and Blood Assimilation Orchestrates Immunomodulation of the Biomineralized Collagen Matrix.

Calcium phosphate-based biomineralized biomaterials have broad application prospects. However, the immune response and foreign body reactions elicited by biomineralized materials have drawn substantial attention recently, contrary to the immune microenvironment optimization concept. Therefore, it is important to clarify the immunomodulation properties of biomineralized materials. Herein, we prepared the biomineralized collagen matrix (BCM) and screened the key immunomodulation factor carboxymethyl chitosan/amorphous calcium phosphate (CMC/ACP) nanocomplex. The immunomodulation effect of the BCM was investigated in vitro and in vivo. The BCM triggered evident inflammatory responses and cascade foreign body reactions by releasing the CMC/ACP nanocomplex, which activated the potential TLR4-MAPK/NF-κB pathway, compromising the collagen matrix biocompatibility. By contrast, blocking the CMC/ACP nanocomplex release via the blood assimilation process of the BCM mitigated the inflammation and foreign body reactions, enhancing biocompatibility. Hence, the immunomodulation of the BCM was orchestrated by the balance between the CMC/ACP nanocomplex and the blood assimilation process. Controlling the release of the CMC/ACP nanocomplex to accord the biological effects of ACP with the temporal regenerative demands is key to developing advanced biomineralized materials.

2-DG Regulates Immune Imbalance on the Titanium Surface after Debridement.

Peri-implantitis requires clinical treatments comprised of mechanical and chemical debridement to remove bacterial biofilms. Bone regeneration on the titanium surface after debridement has been a topical issue of peri-implantitis treatments. Increasing evidence has revealed that the immune microenvironment plays a key role in regulating the bone regeneration process. However, it remains unclear what kind of immune microenvironment the titanium surface induces after debridement. In the study, model titanium surface after debridement was prepared via biofilm induction and mechanical and chemical debridement in vitro. Then, the macrophages and naïve CD4+ T lymphocytes were cultured on the titanium surface after debridement for immune microenvironment evaluation, with the original titanium surface as the control. Next, to regulate the immune microenvironment, 2-DG, a glycolysis inhibitor, was further incorporated to regulate macrophages and CD4+ T lymphocytes at the same time. Surface characterization results showed that the bacterial biofilms were completely removed, while the micro-morphology of titanium surface altered after debridement, and the element composition did not change. Compared with the original titanium disc, titanium surface after debridement can lead to the inflammatory differentiation of macrophages and CD4+ T lymphocytes. The percentage of M1 and Th17 inflammatory cells and the expression of their inflammatory factor genes are upregulated. However, 0.3 mmol of 2-DG can significantly reduce the inflammatory differentiation of both macrophages and CD4+ T lymphocytes and inhibit their expression of inflammatory genes. In conclusion, although bacterial biofilms were removed from titanium surface after debridement, the surface topography changes could still induce immune imbalance and form an inflammatory immune microenvironment. However, this inflammatory immune microenvironment can be effectively reversed by 2-DG in vitro, thus creating an immune microenvironment conducive to osteogenesis, which might provide a new perspective for future therapy of peri-implantitis.

Tailoring the multiscale mechanics of tunable decellularized extracellular matrix (dECM) for wound healing through immunomodulation.

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.

Optimizing the bio-degradability and biocompatibility of a biogenic collagen membrane through cross-linking and zinc-doped hydroxyapatite.

Biogenic collagen membranes have been widely used as soft tissue barriers in guided bone regeneration (GBR) and guided tissue regeneration (GTR). Nevertheless, their clinical performance remains unsatisfactory because of their low mechanical strength and fast degradation rate in vivo. Although cross-linking with chemical agents is effective and reliable for prolonging the degradation time of collagen membranes, some adverse effects including potential cytotoxicity and undesirable tissue integration have been observed during this process. As a fundamental nutritional trace element, zinc plays an active role in promoting the growth of cells and regulating the degradation of the collagen matrix. Herein, a biogenic collagen membrane was cross-linked with glutaraldehyde-alendronate to prolong its degradation time. The physiochemical and biological properties were enhanced by the incorporation of zinc-doped nanohydroxyapatite (nZnHA), with the native structure of collagen preserved. Specifically, the cross-linking combined with the incorporation of 1% and 2% nZnHA seemed to endow the membrane with the most appropriate biocompatibility and tissue integration capability among the cross-linked membranes, as well as offering a degradation period of six weeks in a rat subcutaneous model. Thus, improving the clinical performance of biogenic collagen membranes by cross-linking together with the incorporation of nZnHA is a promising strategy for the improvement of biogenic collagen membranes. STATEMENT OF SIGNIFICANCE: The significance of this research includes.

Enhanced sensitivity of optical fiber vibration sensor based on radio-frequency Michelson interferometer.

We propose and demonstrate a new scheme for enhancing the sensitivity of an optical fiber vibration sensor based on microwave interferometry, which is realized by an incoherent optical Michelson interferometer (MI). The sensing arm of the MI is sensitive to environmental vibration; this will cause changes in the phase of the reflection spectra in the microwave domain. The phase sensitivity can be improved by adjusting the power ratio of the two beams in the interferometer and the driving frequency of the modulator. The system can overcome the problem of interference fading so that it is immune to environmental disturbance. The proposed scheme has merits of simplicity and compact configuration, and may provide a new type of high-precision fiber sensor for measuring vibration, temperature, strain, and so on.

Significant East Asian Affinity of the Sichuan Hui Genomic Structure Suggests the Predominance of the Cultural Diffusion Model in the Genetic Formation Process.

The ancestral origin and genomic history of Chinese Hui people remain to be explored due to the paucity of genome-wide data. Some evidence argues that an eastward migration of Central Asians gave rise to modern Hui people, which is referred to as the demic diffusion hypothesis; other evidence favors the cultural diffusion hypothesis, which posits that East Asians adopted Muslim culture to form the modern culturally distinct populations. However, the extent to which the observed genetic structure of the Huis was mediated by the movement of people or the assimilation of Muslim culture also remains highly contentious. Analyses of over 700 K SNPs in 109 western Chinese individuals (49 Sichuan Huis and 60 geographically close Nanchong Hans) together with the available ancient and modern Eurasian sequences allowed us to fully explore the genomic makeup and origin of Hui and neighboring Han populations. The results from PCA, ADMIXTURE, and allele-sharing-based f-statistics revealed a strong genomic affinity between Sichuan Huis and Neolithic-to-modern Northern East Asians, which suggested a massive gene influx from East Asians into the Sichuan Hui people. Three-way admixture models in the qpWave/qpAdm analyses further revealed a small stream of gene influx from western Eurasians into the Sichuan Hui people, which was further directly confirmed via the admixture event from the temporally distinct Western sources to Sichuan Hui people in the qpGraph-based phylogenetic model, suggesting the key role of the cultural diffusion model in the genetic formation of the Sichuan Huis. ALDER-based admixture date estimation showed that this observed western Eurasian admixture signal was introduced into the Sichuan Huis during the historic periods, which was concordant with the extensive western-eastern communication along the Silk Road and historically documented Huis' migration history. In summary, although significant cultural differentiation exists between Hui people and their neighbors, our genomic analysis showed their strong genetic affinity with modern and ancient Northern East Asians. Our results support the hypothesis that the Sichuan Huis arose from a mixture of minor western Eurasian ancestry and predominant East Asian ancestry.