Investigation of anti-adhesion ability of 8-arm PEGNHS-modified porcine pericardium.

In post-adhesion surgery, there is a clinical need for anti-adhesion membranes specifically designed for the liver, given the limited efficacy of current commercial products. To address this demand, we present a membrane suitable for liver surgery applications, fabricated through the modification of decellularized porcine pericardium with 20 KDa hexaglycerol octa (succinimidyloxyglutaryl) polyoxyethylene (8-arm PEGNHS). We also developed an optimized modification procedure to produce a high-performance anti-adhesion barrier. The modified membrane significantly inhibited fibroblast cell adherence while maintaining minimal levels of inflammation. By optimizing the modification ratio, we successfully controlled post-adhesion formation. Notably, the 8-arm PEG-modified pericardium with a molar ratio of 5 exhibited the ability to effectively prevent post-adhesion formation on the liver compared to both the control and Seprafilm®, with a low adhesion score of 0.5 out of 3.0. Histological analysis further confirmed its potential for easy separation. Furthermore, the membrane demonstrated regenerative capabilities, as evidenced by the proliferation of mesothelial cells on its surface, endowing anti-adhesion properties between the abdominal wall and liver. These findings highlight the membrane's potential as a reliable barrier for repeated liver resection procedures that require the removal of the membrane multiple times.

Nonvolatile Switching of Large Nonreciprocal Optical Absorption at Shortwave Infrared Wavelengths.

We report large nonreciprocal optical absorption at shortwave infrared (SWIR) wavelengths in the magnetoelectric (ME) antiferromagnet (AFM) LiNiPO_{4}. The difference in absorption coefficients for light propagating in opposite directions, divided by the sum, reaches up to ∼40% at 1450 nm. Moreover, the nonreciprocity is switched by a magnetic field in a nonvolatile manner. Using symmetry considerations, we reveal that the large nonreciprocal absorption is attributed to Ni^{2+} d-d transitions through the spin-orbit coupling. Furthermore, we propose that an even larger nonreciprocity can be achieved for a Ni-based ME AFM where electric dipoles of every NiO_{6} unit and Ni^{2+} spins are orthogonal and, respectively, form a collinear arrangement. This study provides a pathway toward nonvolatile switchable one-way transparency of SWIR light.

Application of a genetically engineered macrophage cell line for evaluating cellular effects of UV/US-treated poly(ethylene terephthalate) microplastics.

Microplastic (MP) pollution is a global environmental problem. To understand the biological effects of MPs on humans, it is essential to evaluate the response of human cells to model plastic particles that mimic environmental MPs in a sensitive and non-invasive manner. In this study, we investigated the preparation of poly(ethylene terephthalate) (PET) fragments with properties similar to those of environmental MPs by combining photo-oxidative degradation via ultraviolet (UV) irradiation with mechanical pulverization and hydrolysis via ultrasound (US) exposure. Combination of UV and US treatments decreased the particle size of PET fragments to 10.2 µm and increased their crystallinity and Young's modulus to 35.7 % and 0.73 GPa, respectively, while untreated PET fragments showed the particle size of 18.9 µm, the crystallinity of 33.7 %, and Young's modulus of 0.48 GPa. In addition, an increase in negative surface potential and O/C ratio were observed for UV/US-treated PET fragments, suggesting surface oxidation via UV/US treatment. Cytokine secretion from human macrophages was evaluated by a highly sensitive inflammation evaluation system using the HiBiT-based chemiluminescence detection method developed by genome editing technology. UV/US-treated PET fragments induced a 1.4 times higher level of inflammatory cytokine secretion on inflammatory macrophages than untreated ones, suggesting that the biological responses of PET fragments could be influenced by changes in material properties via oxidation. In conclusion, UV/US treatment enables efficient preparation of model plastic particles and is expected to provide new insights into the evaluation of biological effects using human cells. (240 words).

Characteristics of macrophage aggregates prepared by rotation culture and their response to polymeric materials.

Understanding the interaction between macrophages and biomaterials is important for the creation of new biomaterials and the development of technologies to control macrophage function. Since macrophages are strongly adhesive, caution is required when performing in vitro evaluations. Similarly, when THP-1 cells, macrophage precursor cells, are differentiated into macrophages using phorbol-12-myristate-13-acetate (PMA), it becomes difficult to detach them from the adherent substrate, which has been a problem on investigation of immunological responses to biomaterials. In this study, the interaction of THP-1 cell-differentiated macrophages with biomaterials was analyzed based on a new method of seeding THP-1 cells. THP-1 cells were cultured in static and rotation culture without and with PMA. In undifferentiated THP-1 cells, there was no change in cellular function between static and rotation cultures. In rotation culture with PMA, THP-1 cells differentiated and formed macrophage aggregates. IL-1ß and MRC1 expression in macrophage aggregates was examined after differentiation and M1/M2 polarization. Macrophage aggregates in rotation culture tended to be polarized toward M2 macrophages compared with those in static culture. In the evaluation of the responses of macrophage aggregates to several kinds of polymeric materials, macrophage aggregates showed different changes in MRC1 expression over time at 30, 50, and 70 rpm. Rotation speed of 30 rpm was considered most appropriate condition in that it gave stable results with the same trend as obtained with static culture. The use of macrophage aggregates obtained by rotational culture is expected to provide new insights into the evaluation of inflammatory properties of biomaterials.

Effect of multi arm-PEG-NHS (polyethylene glycol n-hydroxysuccinimide) branching on cell adhesion to modified decellularized bovine and porcine pericardium.

Implanting physical barrier materials to separate wounds from their surroundings is a promising strategy for preventing postoperative adhesions. Herein, we develop a material that switches from an anti-adhesive surface to an adhesive surface, preventing adhesion in the early stage of transplantation and then promoting recellularization. In this study, 2-arm, 4-arm, and 8-arm poly(ethylene glycol) succinimidyl glutarate (2-, 4-, 8-arm PEG-NHS) were used to modify the surface of decellularized porcine and bovine pericardium. The number of free amines on the surface of each material significantly decreased following modification regardless of the reaction molar ratio of NH2 and NHS, the number of PEG molecule branches, and the animal species of the decellularized tissue. The structure and mechanical properties of the pericardium were maintained after modification with PEG molecules. The time taken for the PEG molecules to detach through hydrolysis of the ester bonds differed between the samples, which resulted in different cell repulsion periods. By adjusting the reaction molar ratio, the number of PEG molecule branches, and the animal species of the decellularized pericardium, the duration of cell repulsion can be controlled and is expected to provide an anti-adhesion material for a variety of surgical procedures.

Detecting Magnetoelectric Effect in a Metallic Antiferromagnet via Nonreciprocal Rotation of Reflected Light.

Certain types of media breaking both space-inversion (P) and time-reversal (T) symmetries but preserving their combination PT exhibit the polarization rotation of reflected light even when that of transmitted light is prohibited. Such an effect is termed nonreciprocal rotation of reflected light (NRR). Although NRR shows nearly the same phenomenon as the magnetooptical Kerr effect or, equivalently, the Hall effect at optical frequencies, its origin is distinct and ascribed to a magnetoelectric (ME) effect at optical frequencies, i.e., the optical ME effect. Here we show the observation of NRR in a metallic antiferromagnet TbB_{4}. The result demonstrates that the ME effect in a metallic system, which is considered to be ill defined, can be detected using reflected light. Furthermore, we spatially resolve antiferromagnetic domains in TbB_{4} by microscope observations of NRR. Our work offers a unique way to probe the ME effect in metallic systems.

Preparation of Cholesterol-Modified Hyaluronic Acid Nanogel-Based Hydrogel and the Inflammatory Evaluation Using Macrophage-like Cells.

Nanogels are candidate biomaterials for tissue engineering and drug delivery. In the present study, a cholesterol-hyaluronic acid hydrogel was developed, and the pro-inflammatory response of macrophages to the hydrogel was investigated to determine its use in biomedical applications. Hyaluronic acid modified with cholesterol (modification rate: 0-15%) and maleimide (Chol-HA) was synthesized. The Chol-HA nanogel was formed through self-assembly via hydrophobic cholesterol interactions in aqueous solution. The Chol-HA hydrogel was formed through chemical crosslinking of the Chol-HA nanogel via a Michael addition reaction between the maleimide and thiol groups of 4arm-PEGSH. We found that the Chol-HA hydrogels with 5, 10, and 15% cholesterol inhibited the pro-inflammatory response of HiBiT-THP-1 cells, suggesting that the cholesterol contributed to the macrophage response. Furthermore, Interleukin 4 (IL-4) encapsulated in the hydrogel of the Chol-HA nanogel enhanced the inhibition of the inflammatory response in HiBiT-THP-1 cells. These results provide useful insights into the biomedical applications of hydrogels.

Non-equilibrium dynamics of spin-lattice coupling.

Quantifying the dynamics of normal modes and how they interact with other excitations is of central importance in condensed matter. Spin-lattice coupling is relevant to several sub-fields of condensed matter physics; examples include spintronics, high-Tc superconductivity, and topological materials. However, experimental approaches that can directly measure it are rare and incomplete. Here we use time-resolved X-ray diffraction to directly access the ultrafast motion of atoms and spins following the coherent excitation of an electromagnon in a multiferroic hexaferrite. One striking outcome is the different phase shifts relative to the driving field of the two different components. This phase shift provides insight into the excitation process of such a coupled mode. This direct observation of combined lattice and magnetization dynamics paves the way to access the mode-selective spin-lattice coupling strength, which remains a missing fundamental parameter for ultrafast control of magnetism and is relevant to a wide variety of materials.

Fabrication of Polypropylene Nanoplastics Via Thermal Oxidation Reaction for Human Cells Responsiveness Studies.

With the current worldwide increasing use of plastics year by year, nanoplastics (NPs) have become a global threat to environmental and public health concerns. Among plastics, polypropylene (PP) is widely used in industrial and medical applications. Owing to the lack of validated detection methods and standard materials for PP NPs, understanding the impact of PP NPs on the environmental and biological systems is still limited. Here, isotactic polypropylene (iPP) was fabricated into oxidized polypropylene micro/nanoplastics (OPPs) via a thermal oxidation using hydrogen peroxide (H2O2) under various heating temperatures. The resulting OPPs were investigated in terms of the size distribution, surface chemistry, morphology, and thermal property as well as their concentration-dependent cytotoxicity to a human intestinal epithelial cell line (Caco-2), which could be a route to uptake NPs into the body through the food chain. The average diameters of the OPPs decrease with increasing reaction temperature. The OPPs obtained at 175 °C (OPP175) were spherical in shape and had a rough surface, with size distributions of approximately 0.14 ± 0.02 µm. A significant increase in the carbonyl content of the oxidized product was confirmed by Fourier transform infrared and X-ray photoelectron spectroscopy analyses. Caco-2 cells were exposed to OPP175 in a dose-dependent manner, and a significant loss of cell viability occurred at the concentration of 100 µg/mL. Thus, this study provides a fundamental approach for the fabrication of a model of NPs for the urgently demanded in vitro and in vivo studies to assess the potential impact of NPs on biological systems.

Electric field-induced magnetochiral dichroism in a ferroaxial crystal.

In a chiral medium, any mirror symmetries are broken, which induces unique physical properties represented by natural optical rotation. When electromagnetic waves propagate through a chiral medium placed in a magnetic field, the refractive index, or equivalently, the absorption encountered by the electromagnetic waves differs depending on whether it travels parallel or antiparallel to the magnetic field. Such a phenomenon is known as magnetochiral dichroism (MChD), which is the characteristic interplay between chirality and magnetism. Similar to chirality, the so-called ferroaxial order, an emergent ferroic state of crystalline materials, is also characterized by mirror symmetry breaking. In contrast to chiral materials, however, the mirror symmetry perpendicular to the crystalline principal axis is allowed in ferroaxial materials. In other words, chirality and thus phenomena unique to chirality can be induced by breaking the remaining mirror symmetry by applying an electric field. Here, we show electric control of chirality and resulting electric field-induced MChD (E-MChD) of the short-wavelength infrared region in a ferroaxial crystal, NiTiO3. We performed spectroscopy measurements of E-MChD by taking a difference of absorption coefficients obtained with and without electric and magnetic fields. As a result, E-MChD was observed around the excitation energy corresponding to Ni2+ d-d magnetic-dipole transitions. The result is nicely explained by adopting the theory of MChD concerning the pseudo-Stark splitting of the energy state. Ferroaxial materials therefore provide platforms to achieve electric control of chirality-related phenomena.

Effect of Pressure Conditions in Uterine Decellularization Using Hydrostatic Pressure on Structural Protein Preservation.

Uterine regeneration using decellularization scaffolds provides a novel treatment for uterine factor infertility. Decellularized scaffolds require maximal removal of cellular components and minimal damage to the extracellular matrix (ECM). Among many decellularization methods, the hydrostatic pressure (HP) method stands out due to its low cytotoxicity and superior ECM preservation compared to the traditional detergent methods. Conventionally, 980 MPa was utilized in HP decellularization, including the first successful implementation of uterine decellularization previously reported by our team. However, structural protein denaturation caused by exceeding pressure led to a limited regeneration outcome in our previous research. This factor urged the study on the effects of pressure conditions in HP methods on decellularized scaffolds. The authors, therefore, fabricated a decellularized uterine scaffold at varying pressure conditions and evaluated the scaffold qualities from the perspective of cell removal and ECM preservation. The results show that by using lower decellularization pressure conditions of 250 MPa, uterine tissue can be decellularized with more preserved structural protein and mechanical properties, which is considered to be promising for decellularized uterine scaffold fabrication applications.

Photothermal therapeutic ability of copper open-shell nanostructures that are effective in the second biological transparency window based on symmetry breaking-induced plasmonic properties.

In this study, a photothermal therapy agent that works efficiently in the second biological transparency window was developed based on the localized surface plasmon (LSP) resonance of symmetry-broken open-shell nanostructures of low-cost Cu (CuOSNs). The strong LSP resonance and superior photothermal conversion ability in the second biological transparency window were achieved by generating the dipolar bonding mode due to the plasmon hybridization between the nanoshell dipole and the nanohole dipole at the opening edge in CuOSNs derived from the symmetry breaking of a Cu nanoshell. Oxidative dissolution of CuOSNs in water was significantly suppressed by successive coating with the self-assembled monolayer of 16-mercaptohexadecanoic acid and a thin silica layer. Furthermore, the stability in phosphate buffered saline, which models the biological environment, was attained by further coating the nanoparticles with polyethylene glycol. It was demonstrated from in vitro cell tests using HeLa cells that the cytotoxicity of CuOSNs was effectively suppressed by the surface protection. The viability of HeLa cells incubated with CuOSNs was decreased under the irradiation of low intensity 1060 nm laser with increasing number of CuOSNs. These results demonstrate that low-cost symmetry-broken Cu-based nanostructures can act as an excellent photothermal therapy agent in the second biological transparency window.

Mechanoregulation of Osteoclastogenesis-Inducing Potentials of Fibrosarcoma Cell Line by Substrate Stiffness.

A micro-physiological system is generally fabricated using soft materials, such as polydimethylsiloxane silicone (PDMS), and seeks an inflammatory osteolysis model for osteoimmunological research as one of the development needs. Microenvironmental stiffness regulates various cellular functions via mechanotransduction. Controlling culture substrate stiffness may help spatially coordinate the supply of osteoclastogenesis-inducing factors from immortalized cell lines, such as mouse fibrosarcoma L929 cells, within the system. Herein, we aimed to determine the effects of substrate stiffness on the osteoclastogenesis-inducing potential of L929 cells via cellular mechanotransduction. L929 cells showed increased expression of osteoclastogenesis-inducing factors when cultured on type I collagen-coated PDMS substrates with soft stiffness, approximating that of soft tissue sarcomas, regardless of the addition of lipopolysaccharide to augment proinflammatory reactions. Supernatants of L929 cells cultured on soft PDMS substrates promoted osteoclast differentiation of the mouse osteoclast precursor RAW 264.7 by stimulating the expression of osteoclastogenesis-related gene markers and tartrate-resistant acid phosphatase activity. The soft PDMS substrate inhibited the nuclear translocation of YES-associated proteins in L929 cells without reducing cell attachment. However, the hard PDMS substrate hardly affected the cellular response of the L929 cells. Our results showed that PDMS substrate stiffness tuned the osteoclastogenesis-inducing potential of L929 cells via cellular mechanotransduction.

Chemical Aspect of Displacive-Type Ferroaxial Phase Transition from Perspective of Second-Order Jahn-Teller Effect: NASICON Systems as an Example.

Ferroaxial order, characterized by a rotational arrangement of electric dipoles, attracts increasing attention in terms of a new family of ferroic orders. However, there has been no chemical guideline for exploring crystalline materials showing ferroaxial order, namely ferroaxial materials. Here, we present a chemical guideline grounded in staggered polyhedral connectivity, which we propose as a structural prerequisite for ferroaxial order, and the second-order Jahn-Teller (SOJT) theory extended from molecular orbitals to electronic band structures. Na-superionic conductors (NASICON) including NaM2(PO4)3 (M = early-transition or post-transition metal) are identified as potential ferroaxial materials because of their staggered structures composed of MO6 octahedra and PO4 tetrahedra. However, ferroaxial phase transitions hardly occur in some of the NASICON systems, which offers a platform to uncover a hidden factor playing an important role in driving this system into ferroaxial states. Our first-principles calculations demonstrate that a ferroaxial phase transition in NASICON systems occurs only when SOJT interaction is symmetrically allowed, that is, energy-lowering chemical bonds are formed as a consequence of the distortion. Our proposals would be not limited to NASICON systems but applicable to a variety of compounds and provide new insight into the exploration of displacive-type ferroaxial materials.

Substrate stiffness controls proinflammatory responses in human gingival fibroblasts.

Soft gingiva is often compromised in gingival health; however, the underlying biological mechanisms remain unknown. Extracellular matrix (ECM) stiffness is involved in the progression of various fibroblast-related inflammatory disorders via cellular mechanotransduction. Gingival stiffness might regulate cellular mechanotransduction-mediated proinflammatory responses in gingival fibroblasts. This in vitro study aims to investigate the effects of substrate stiffness on proinflammatory responses in human gingival fibroblasts (hGFs). The hGFs isolated from two healthy donors cultured on type I collagen-coated polydimethylsiloxane substrates with different stiffnesses, representing soft (5 kPa) or hard (25 kPa) gingiva. Expression levels of proinflammatory mediators, prostaglandin E2 or interleukin-1ß, in hGFs were significantly higher with the soft substrate than with the hard substrate, even without and with lipopolysaccharide (LPS) to induce inflammation. Expression levels of gingival ECM and collagen cross-linking agents in hGFs were downregulated more with the soft substrate than with the hard substrate through 14 days of culture. The soft substrate suppressed the expression of mechanotransduction-related transcriptional factors and activated the expression of inflammation-related factors, whereas the hard substrate demonstrated the opposite effects. Soft substrate induced proinflammatory responses and inhibition of ECM synthesis in hGFs by inactivating cellular mechanotransduction. This supports the importance of ECM stiffness in gingival health.

Preparation of mineralized pericardium by alternative soaking for soft-hard interregional tissue application.

Recent applications of decellularized tissues include the ectopic use of sheets and powders for three-dimensional (3D) tissue reconstruction. Decellularized tissues are modified (or fabricated) with the desired functions for application to the target (transplanted or used) tissue, including soft-hard interregional tissues, such as ligaments, tendons, and periodontal ligaments. This study aimed to prepare a mineralized decellularized pericardium to construct a soft-hard interregional tissue by 3D fabrication of decellularized pericardium, for example, rolling up to a cylindrical form. The decellularized pericardial tissue was prepared using the high hydrostatic pressurization (HHP) and surfactants method. The pericardium consisted of bundles of aligned fibers, and the bundles were slightly disordered when prepared with the surfactant decellularization method compared with that prepared using the HHP decellularization method. Mineralization of the decellularized pericardium was performed using an alternate soaking process with various cycles. The surface of the decellularized pericardium was covered with calcium phosphate precipitates, which accumulated on the surface with an increasing number of soaking cycles. The inside of the HHP decellularized pericardium was mineralized uniformly, whereas the mineralization of the decellularized pericardium decreased toward the interior. These findings suggest that the decellularization method strongly affects the structure and mineralized parts of the decellularized pericardium. The mineralized decellularized pericardium could be a candidate material for reconstructing alternative interregional tissues, such as ligaments and tendons.

A novel approach for the endothelialization of xenogeneic decellularized vascular tissues by human cells utilizing surface modification and dynamic culture.

Decellularized xenogeneic vascular grafts can be used in revascularization surgeries. We have developed decellularization methods using high hydrostatic pressure (HHP), which preserves the extracellular structure. Here, we attempted ex vivo endothelialization of HHP-decellularized xenogeneic tissues using human endothelial cells (ECs) to prevent clot formation against human blood. Slices of porcine aortic endothelium were decellularized using HHP and coated with gelatin. Human umbilical vein ECs were directly seeded and cultured under dynamic flow or static conditions for 14 days. Dynamic flow cultures tend to demonstrate higher cell coverage. We then coated the tissues with the E8 fragment of human laminin-411 (hL411), which has high affinity for ECs, and found that Dynamic/hL411showed high area coverage, almost reaching 100% (Dynamic/Gelatin vs Dynamic/hL411; 58.7 ± 11.4 vs 97.5 ± 1.9%, P = 0.0017). Immunostaining revealed sufficient endothelial cell coverage as a single cell layer in Dynamic/hL411. A clot formation assay using human whole blood showed low clot formation in Dynamic/hL411, almost similar to that in the negative control, polytetrafluoroethylene. Surface modification of HHP-decellularized xenogeneic endothelial tissues combined with dynamic culture achieved sufficient ex vivo endothelialization along with prevention of clot formation, indicating their potential for clinical use as vascular grafts in the future.

Identification of the Factor That Leads Human Mesenchymal Stem Cell Lines into Decellularized Bone.

Hematopoiesis is maintained by the interaction of hematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (MSCs) in bone marrow microenvironments, called niches. Certain genetic mutations in MSCs, not HSCs, provoke some hematopoietic neoplasms, such as myelodysplastic syndrome. An in vivo bone marrow niche model using human MSC cell lines with specific genetic mutations and bone scaffolds is necessary to elucidate these interactions and the disease onset. We focused on decellularized bone (DCB) as a useful bone scaffold and attempted to induce human MSCs (UE7T-9 cells) into the DCB. Using the CRISPR activation library, we identified SHC4 upregulation as a candidate factor, with the SHC4 overexpression in UE7T-9 cells activating their migratory ability and upregulating genes to promote hematopoietic cell migration. This is the first study to apply the CRISPR library to engraft cells into decellularized biomaterials. SHC4 overexpression is essential for engrafting UE7T-9 cells into DCB, and it might be the first step toward creating an in vivo human-mouse hybrid bone marrow niche model.

Extraction and Biological Evaluation of Matrix-Bound Nanovesicles (MBVs) from High-Hydrostatic Pressure-Decellularized Tissues.

Decellularized tissues are widely used as promising materials in tissue engineering and regenerative medicine. Research on the microstructure and components of the extracellular matrix (ECM) was conducted to improve the current understanding of decellularized tissue functionality. The presence of matrix-bound nanovesicles (MBVs) embedded within the ECM was recently reported. Results of a previous experimental investigation revealed that decellularized tissues prepared using high hydrostatic pressure (HHP) exhibited good in vivo performance. In the current study, according to the hypothesis that MBVs are one of the functional components in HHP-decellularized tissue, we investigated the extraction of MBVs and the associated effects on vascular endothelial cells. Using nanoparticle tracking assay (NTA), transmission electron microscopy (TEM), and RNA analysis, nanosized (100-300 nm) and membranous particles containing small RNA were detected in MBVs derived from HHP-decellularized small intestinal submucosa (SIS), urinary bladder matrix (UBM), and liver. To evaluate the effect on the growth of vascular endothelial cells, which are important in the tissue regeneration process, isolated SIS-derived MBVs were exposed to vascular endothelial cells to induce cell proliferation. These results indicate that MBVs can be extracted from HHP-decellularized tissues and may play a significant role in tissue remodeling.

Titanium Nanosurface with a Biomimetic Physical Microenvironment to Induce Endogenous Regeneration of the Periodontium.

The periodontium supports the teeth by dentoalveolar fibrous joints that serve unique oral functions. Endogenous regeneration of the periodontium around artificial teeth (dental implants) provides a cost-effective solution for the extension of healthy life expectancy but remains a challenge in regenerative medicine. Biomimetics can create smart biomaterials that tune endogenous cells at a tissue-material interface. Here, we created a smart titanium nanosurface mimicking the surface nanotopography and micromechanical properties of the tooth root cementum (TRC), which is essential for the induction of dentoalveolar fibrous joints to regenerate the periodontium. After transplantation into the rat renal capsule, only the titanium artificial tooth with the TRC-mimetic nanosurface formed a complex dentoalveolar fibrous joint structure, with bone tissue, periodontal ligament (PDL), and TRC, in the decellularized jawbone matrix. TRC-mimetic titanium implants induce the formation of functional periodontium, even in a jawbone implantation model, which generally causes osseointegration (ankyloses). In human PDL cells, TRC analogousness in the surface mechanical microenvironment regulates matrix mineralization through bone sialoprotein expression and phosphorus metabolism, which are critical for cementogenesis. Therefore, the titanium nanosurfaces with nanotopographical and mechanical microenvironments mimicking the TRC surface induce dentoalveolar fibrous joints for periodontal regeneration by interfacial tuning of endogenous cells.