A Cyclical Magneto-Responsive Massage Dressing for Wound Healing.

Tissue development is mediated by a combination of mechanical and biological signals. Currently, there are many reports on biological signals regulating repair. However, insufficient attention is paid to the process of mechanical regulation, especially the active mechanical regulation in vivo, which has not been realized. Herein, a novel dynamically regulated repair system for both in vitro and in vivo applications is developed, which utilizes magnetic nanoparticles as non-contact actuators to activate hydrogels. The magnetic hydrogel can be periodically activated and deformed to different amplitudes by a dynamic magnetic system. An in vitro skin model is used to explore the impact of different dynamic stimuli on cellular mechano-transduction signal activation and cell differentiation. Specifically, the effect of mechanical stimulation on the phenotypic transition of fibroblasts to myofibroblasts is investigated. Furthermore, in vivo results verify that dynamic massage can simulate and enhance the traction effect in skin defects, thereby accelerating the wound healing process by promoting re-epithelialization and mediating dermal contraction.

A Spatiotemporal Controllable Biomimetic Skin for Accelerating Wound Repair.

Skin injury repair is a dynamic process involving a series of interactions over time and space. Linking human physiological processes with materials' changes poses a significant challenge. To match the wound healing process, a spatiotemporal controllable biomimetic skin is developed, which comprises a three-dimensional (3D) printed membrane as the epidermis, a cell-containing hydrogel as the dermis, and a cytokine-laden hydrogel as the hypodermis. In the initial stage of the biomimetic skin repair wound, the membrane frame aids wound closure through pre-tension, while cells proliferate within the hydrogel. Next, as the frame disintegrates over time, cells released from the hydrogel migrate along the residual membrane. Throughout the process, continuous cytokines release from the hypodermis hydrogel ensures comprehensive nourishment. The findings reveal that in the rat full-thickness skin defect model, the biomimetic skin demonstrated a wound closure rate eight times higher than the blank group, and double the collagen content, particularly in the early repair process. Consequently, it is reasonable to infer that this biomimetic skin holds promising potential to accelerate wound closure and repair. This biomimetic skin with mechanobiological effects and spatiotemporal regulation emerges as a promising option for tissue regeneration engineering.

Enabling endogenous distributed acoustic sensing in a digital subcarrier coherent transmission system.

To monitor the health of the fiber network and its ambient environment in densely populated access/metro network areas, in this Letter, an endogenous distributed acoustic sensing (DAS) has been proposed and achieved in a coherent digital subcarrier multiplexing (DSCM) system. Rather than specially allocating a sensing probe in general integrated communication and sensing schemes, the fractional Fourier transformed (FrFT) training sequence (TS) designated for time/frequency synchronization in DSCM coherent communications has been repurposed for sensing. While achieving excellent synchronization performance of communication, the FrFT-based TS can also be concurrently utilized to perform distributed vibration sensing. Experimental results demonstrate that the FrFT-based timing/frequency synchronization sequence is repurposed to achieve a DAS sensitivity of 70 p ε/Hz at a spatial resolution of 5 m, along with 100-Gb/s 16 quadrature amplitude modulation (QAM) DSCM transmission, without a loss of spectral efficiency.

Blind SOP recovery of eigenvalue communication system based on a nonlinear Fourier transform.

Owing to the random birefringence of optical fibers, the recovery of the state of polarization (SOP) is urgently needed, especially in the nonlinear spectrum division multiplexing transmissions. Based on the variance of the polarization power ratio among symbols as the cost function, we propose a novel algorithm for the blind SOP recovery of eigenvalue communications. In the single eigenvalue transmissions with phase-shift keying or 16-ary amplitude and phase-shift keying constellations, at least 25.3 dB polarization extinction ratio can be achieved by using a block length of 30, even under 7 dB OSNR condition. It also shows that the proposed algorithm can be employed in multi-eigenvalue NFDM transmissions and full-spectrum modulated NFDM system. In the experiment, our proposed algorithm performs the same as the training symbol based method in back-to-back and less than 3000 km fiber link conditions; a maximum performance gain of 1.6 dB was obtained in ultra-long-haul condition (4300 km). It also shows that the impact of the polarization mode dispersion of a single-mode fiber on the algorithm is negligible.

Enabling cost-effective high-performance vibration sensing in digital subcarrier multiplexing systems.

Enabling communication networks with sensing functionality has attracted significant interest lately. The digital subcarrier multiplexing (DSCM) technology is widely promoted in short-reach scenarios for its inherent flexibility of fine-tuning the spectrum. Its compatibility with large-scale as-deployed coherent architectures makes it particularly suited for cost-sensitive integrated sensing and communication applications. In this paper, we propose a scheme of spectrally integrating the digital linear frequency modulated sensing signal into DSCM signals to achieve simultaneous sensing and communication through shared transmitter. Consequently, this cost-effective scheme has been demonstrated to achieve 100-Gb/s dual-polarization quadrature phase-shift keying (DP-QPSK) and 200-Gb/s dual-polarization 16-ary quadrature amplitude modulation (DP-16QAM) transmission with a distributed acoustic sensing sensitivity of 69 pε/Hz and 88 pε/Hz respectively, at a spatial resolution of 4 m.

Adaptive bias control of optical IQ modulator with low LFM dither and strong fluctuation resistance.

An innovative approach has been proposed for adaptive bias control in optical IQ modulators. In contrast to traditional approaches that utilize sine dither, this method employs a linear frequency modulated (LFM) signal as the dither, associated with the fractional Fourier Transform (FrFT) to extract the bias point drift. The LFM signal, after undergoing FrFT, transforms into a compressed signal (CS) with energy concentration in the fractional domain. Utilizing this signal for bias point monitoring, the proposed method demonstrates robust bias control even in the presence of substantial interferences, as substantiated by comprehensive simulations and experimental investigations. Remarkably, in a 20-Gbaud 16QAM signal transmission, the proposed approach achieves stable control of the bias point for over 4 hours, even in the presence of voltage fluctuations, while effectively reducing the dither amplitude by half. Furthermore, it maintains a low bit error rate (BER) below 10-5 even under intentional external interference.

PDM-SHD NFDM transmission with envelope-detection feedback polarization tracking and optical injection locking.

Nonlinear frequency division multiplexing (NFDM) systems, especially the eigenvalue communications have the potential to overcome the nonlinear Shannon capacity limit. However, the baud rate of eigenvalue communications is typically restricted to a few GBaud, making it challenging to mitigate laser frequency impairments such as the phase noise and frequency offset (FO) using digital signal processing (DSP) algorithms in intradyne detections (IDs). Therefore, we introduce the polarization division multiplexing-self-homodyne detection (PDM-SHD) into the NFDM link, which could overcome the impact of phase noise and FO by transmitting a pilot carrier originating from the transmitter laser to the receiver through the orthogonal polarization state of signal. To separate the signal from the carrier at the receiver, a carrier to signal power ratio (CSPR) unrestricted adaptive polarization controlling strategy is proposed and implemented by exploiting the optical intensity fluctuation of the light in a particular polarization rather than its direct optical power as the feedback. Optical injection locking (OIL) is used subsequently to amplify optical power of pilot carrier and mitigate the impact of signal-signal beat interference (SSBI). Additionally, the effects of cross-polarization modulation (XPolM) and modulation instability (MI) in long haul transmission are explored and inhibited. The results show that the tolerable FO range is about 3.5 GHz, which is 17 times larger than the ID one. When 16-amplitude phase shift keying (APSK) or 64-APSK constellations are used, identical Q-factor performance can be obtained by using distributed feedback (DFB, ∼10 MHz) laser, external cavity laser (ECL, ∼100kHz), or fiber laser (FL, ∼100 Hz), respectively, which demonstrates that our proposed PDM-SHD eigenvalue communication structure is insensitive to the laser linewidth. Under the impact of cycle slip, the Q-factor difference of 16-APSK signal between the ECL-ID system and ECL-SHD system can be up to 8.73 dB after 1500 km transmission.

All-optical wavelength conversion of a 92-Gb/s 16-QAM signal within the C-band in a single thin-film PPLN waveguide.

Tunable all-optical wavelength conversion (AOWC) within 151 nm bandwidth is demonstrated in a thin-film periodically poled lithium niobate (PPLN) waveguide, which utilizes the cascaded second-harmonic generation and difference-frequency generation (cSHG/DFG) process. Also, in the same waveguide, AOWC of a 92-Gb/s 16-ary quadrature amplitude modulated (16-QAM) signal within the C-band is successfully achieved. For Bit-error ratio (BER) measurements, we obtain a negligible optical signal-to-noise ratio (OSNR) penalty (<0.2 dB) for the converted idler wave at a BER of 1e-3.

Therapeutic Potential of Synthetic Human ß-Defensin 1 Short Motif Pep-B on Lipopolysaccharide-Stimulated Human Dental Pulp Stem Cells.

Dental pulp inflammation is a widespread public problem usually caused by caries or trauma. Alleviating inflammation is critical to inflamed pulp repair. Human ß-defensin 1 short motif Pep-B is a cationic peptide that has anti-inflammatory, antibacterial, and immunoregulation properties, but its repair effect on human dental pulp stem cells (hDPSCs) under inflammation remains unclear. In this study, we aimed to investigate anti-inflammatory function of Pep-B and explore its therapeutic potential in lipopolysaccharide-(LPS-) induced hDPSCs. CCK-8 assay and transwell assay evaluated effects of Pep-B on hDPSC proliferation and chemotaxis. Inflammatory response in hDPSCs was induced by LPS; after Pep-B application, lactate dehydrogenase release, intracellular ROS, inflammatory factor genes expression and possible signaling pathway were measured. Then, osteo-/odontoblast differentiation effect of Pep-B on LPS-induced hDPSCs was detected. The results showed that Pep-B promoted hDPSC proliferation and reduced LPS-induced proinflammatory marker expression, and western blot result indicated that Pep-B inhibited inflammatory activation mediated by NF-κB and MAPK pathways. Pep-B also enhanced the expression of the osteo-/odontogenic genes and proteins, alkaline phosphatase activity, and nodule mineralization in LPS-stimulated hDPSCs. These findings indicate that Pep-B has anti-inflammatory activity and promote osteo-/odontoblastic differentiation in LPS-induced inflammatory environment and may have a potential role of hDPSCs for repair and regeneration.

Human ß-defensins and their synthetic analogs: Natural defenders and prospective new drugs of oral health.

As a family of cationic host defense peptides, human ß-defensins (HBDs) are ubiquitous in the oral cavity and are mainly synthesized primarily by epithelial cells, serving as the primary barrier and aiming to prevent microbial invasion, inflammation, and disease while maintaining physiological homeostasis. In recent decades, there has been great interest in their biological functions, structure-activity relationships, mechanisms of action, and therapeutic potential in oral diseases. Meanwhile, researchers are dedicated to improving the properties of HBDs for clinical application. In this review, we first describe the classification, structural characteristics, functions, and mechanisms of HBDs. Next, we cover the role of HBDs and their synthetic analogs in oral diseases, including dental caries and pulp infections, periodontitis, peri-implantitis, fungal/viral infections and oral mucosal diseases, and oral squamous cell carcinoma. Finally, we discuss the limitations and challenges of clinical translation of HBDs and their synthetic analogs, including, but not limited to, stability, bioavailability, antimicrobial activity, resistance, and toxicity. Above all, this review summarizes the biological functions, mechanisms of action, and therapeutic potential of both natural HBDs and their synthetic analogs in oral diseases, as well as the challenges associated with clinical translation, thus providing substantial insights into the laboratory development and clinical application of HBDs in oral diseases.

Intrafibrillar Mineralization and Immunomodulatory for Synergetic Enhancement of Bone Regeneration via Calcium Phosphate Nanocluster Scaffold.

Inspired by the bionic mineralization theory, organic-inorganic composites with hydroxyapatite nanorods orderly arranged along collagen fibrils have attracted extensive attention. Planted with an ideal bone scaffold will contribute greatly to the osteogenic microenvironment; however, it remains challenging to develop a biomimetic scaffold with the ability to promote intrafibrillar mineralization and simultaneous regulation of immune microenvironment in situ. To overcome these challenges, a scaffold containing ultra-small particle size calcium phosphate nanocluster (UsCCP) is prepared, which can enhance bone regeneration through the synergetic effect of intrafibrillar mineralization and immunomodulatory. By efficient infiltration into collagen fibrils, the UsCCP released from the scaffold achieves intrafibrillar mineralization. It also promotes the M2-type polarization of macrophages, leading to an immune microenvironment with both osteogenic and angiogenic potential. The results confirm that the UsCCP scaffold has both intrafibrillar mineralization and immunomodulatory effects, making it a promising candidate for bone regeneration.

Hyaluronic acid-mediated collagen intrafibrillar mineralization and enhancement of dentin remineralization.

Non-collagenous proteins (NCPs) in the extracellular matrix (ECM) of bone and dentin are known to play a critical regulatory role in the induction of collagen fibril mineralization and are embedded in hyaluronic acid (HA), which acts as a water-retaining glycosaminoglycan and provides necessary biochemical and biomechanical cues. Our previous study demonstrated that HA could regulate the mineralization degree and mechanical properties of collagen fibrils, yet its kinetics dynamic mechanism on mineralization is under debate. Here, we further investigated the role of HA on collagen fibril mineralization and the possible mechanism. The HA modification can significantly promote intrafibrillar collagen mineralization by reducing the electronegativity of the collagen surface to enhance calcium ions (Ca2+) binding capacity to create a local higher supersaturation. In addition, the HA also provides additional nucleation sites and shortens the induction time of amorphous calcium phosphate (ACP)-mediated hydroxyapatite (HAP) crystallization, which benefits mineralization. The acceleration effect of HA on intrafibrillar collagen mineralization is also confirmed in collagen hydrogel and in vitro dentin remineralization. These findings offer a physicochemical view of the regulation effect of carbohydrate polymers in the body on biomineralization, the fine prospect for an ideal biomaterial to repair collagen-mineralized tissues.

An injectable photopolymerizable chitosan hydrogel doped anti-inflammatory peptide for long-lasting periodontal pocket delivery and periodontitis therapy.

Periodontitis is a common chronic inflammatory disease caused by plaque that leads to alveolar bone resorption and tooth loss. Inflammation control and achieving better tissue repair are the key to periodontitis treatment. In this study, human ß-Defensin 1 short motif Pep-B with inflammation inhibition and differentiation regulation properties, is firstly used in the treatment of periodontitis, and an injectable photopolymerizable Pep-B/chitosan methacryloyl composite hydrogel (CMSA/Pep-B) is constructed. We confirm that Pep-B improves inflammation, and restores osteogenic behavior and function of injured stem cells. CMSA/Pep-B has good injectability, fluidity and photopolymerizability, and can sustainably release Pep-B to maintain drug concentration in periodontal pockets. Furthermore, animal experiments showed that CMSA/Pep-B significantly ameliorated the inflammation of the periodontium and reduced the alveolar bone loss by decreasing inflammatory infiltration, osteoclast formation and collagen destruction. In conclusion, CMSA/Pep-B is envisaged to be a novel bioactive material or therapeutic drug for treating periodontitis.

Gelatin-Based Metamaterial Hydrogel Films with High Conformality for Ultra-Soft Tissue Monitoring.

Implantable hydrogel-based bioelectronics (IHB) can precisely monitor human health and diagnose diseases. However, achieving biodegradability, biocompatibility, and high conformality with soft tissues poses significant challenges for IHB. Gelatin is the most suitable candidate for IHB since it is a collagen hydrolysate and a substantial part of the extracellular matrix found naturally in most tissues. This study used 3D printing ultrafine fiber networks with metamaterial design to embed into ultra-low elastic modulus hydrogel to create a novel gelatin-based conductive film (GCF) with mechanical programmability. The regulation of GCF nearly covers soft tissue mechanics, an elastic modulus from 20 to 420 kPa, and a Poisson's ratio from - 0.25 to 0.52. The negative Poisson's ratio promotes conformality with soft tissues to improve the efficiency of biological interfaces. The GCF can monitor heartbeat signals and respiratory rate by determining cardiac deformation due to its high conformability. Notably, the gelatin characteristics of the biodegradable GCF enable the sensor to monitor and support tissue restoration. The GCF metamaterial design offers a unique idea for bioelectronics to develop implantable sensors that integrate monitoring and tissue repair and a customized method for endowing implanted sensors to be highly conformal with soft tissues.

Extracellular vesicles derived from neural EGFL-Like 1-modified mesenchymal stem cells improve acellular bone regeneration via the miR-25-5p-SMAD2 signaling axis.

Stem cell based transplants effectively regenerate tissues; however, limitations such as immune rejection and teratoma formation prevent their application. Extracellular vesicles (EVs)-mediated acellular tissue regeneration is a promising alternative to stem cell based transplants. Although neural EGFL-like 1 (Nell1) is known to contribute to the osteogenic differentiation of bone marrow stem cells (BMSCs), it remains unknown whether EVs are involved in this process. Here, we present that EVs derived from Nell1-modified BMSCs (Nell1/EVs) have a stronger ability to promote BMSC osteogenesis owing to miR-25-5p downregulation. MiR-25-5p inhibits osteogenesis by targeting Smad2 and suppressing the SMAD and extracellular signal-related kinase 1 and 2 (ERK1/2) pathway activation. In addition, we demonstrate that the 3D-Nell1/EV-hydrogel system is beneficial for bone regeneration in vivo, probably stemming from a slow, continuous release and high concentration of EVs in the bone defect area. Thus, our results have shown the potential of Nell1/EVs as a novel acellular bone regeneration strategy. Mechanistically, the identification of miR-25-5p-SMAD2 signaling axis expands the knowledge of Nell1/EVs induced osteogenesis.

Intraosseous Injection of Calcium Phosphate Polymer-Induced Liquid Precursor Increases Bone Density and Improves Early Implant Osseointegration in Ovariectomized Rats.

PURPOSE: Osteoporosis, due to bone loss and structural deterioration, is a risk factor for dental implant failure, as it impedes initial stability and osseointegration. We aim to assess the effects of calcium phosphate polymer-induced liquid precursor (CaP-PILP) treatment, which significantly increases bone density and improves early implant osseointegration in ovariectomized rats. METHODS: In this study, CaP-PILP was synthesized and characterized through TEM, FTIR and XRD. A rat model of osteoporosis was generated by ovariectomy. CaP-PILP or hydroxyapatite (HAP, negative control) was injected into the tibia, and the resulting changes in bone quality were determined. Further, implants were installed in the treated tibias, and implantation characteristics were assessed after 4 weeks. RESULTS: The CaP-PILP group had superior bone repair. Importantly, CaP-PILP had excellent properties, similar to those of normal bone, in terms of implant osseointegration. In vivo experiment displayed that CaP-PILP group had better bone contact rate (65.97±3.176) than HAP and OVX groups. Meanwhile, a mound of mature and continuous new bone formed. Moreover, the values of BIC and BA showed no significant difference between the CaP-PILP group and the sham group. CONCLUSION: In summary, CaP-PILP is a promising material for application in poor-quality bones to improve implant success rates in patients with osteoporosis. This research provides new perspectives on the application of nano-apatite materials in bone repair.

Engineered osteoclasts as living treatment materials for heterotopic ossification therapy.

Osteoclasts (OCs), the only cells capable of remodeling bone, can demineralize calcium minerals biologically. Naive OCs have limitations for the removal of ectopic calcification, such as in heterotopic ossification (HO), due to their restricted activity, migration and poor adhesion to sites of ectopic calcification. HO is the formation of pathological mature bone within extraskeletal soft tissues, and there are currently no reliable methods for removing these unexpected calcified plaques. In the present study, we develop a chemical approach to modify OCs with tetracycline (TC) to produce engineered OCs (TC-OCs) with an enhanced capacity for targeting and adhering to ectopic calcified tissue due to a broad affinity for calcium minerals. Unlike naive OCs, TC-OCs are able to effectively remove HO both in vitro and in vivo. This achievement indicates that HO can be reversed using modified OCs and holds promise for engineering cells as "living treatment agents" for cell therapy.