Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion: A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Neuromodulation of inhibitory control using phase-lagged transcranial alternating current stimulation.

BACKGROUND: Transcranial alternating current stimulation (tACS) is a prominent non-invasive brain stimulation method for modulating neural oscillations and enhancing human cognitive function. This study aimed to investigate the effects of individualized theta tACS delivered in-phase and out-of-phase between the dorsal anterior cingulate cortex (dACC) and left dorsolateral prefrontal cortex (lDLPFC) during inhibitory control performance. METHODS: The participants engaged in a Stroop task with phase-lagged theta tACS over individually optimized high-density electrode montages targeting the dACC and lDLPFC. We analyzed task performance, event-related potentials, and prestimulus electroencephalographic theta and alpha power. RESULTS: We observed significantly reduced reaction times following out-of-phase tACS, accompanied by reduced frontocentral N1 and N2 amplitudes, enhanced parieto-occipital P1 amplitudes, and pronounced frontocentral late sustained potentials. Out-of-phase stimulation also resulted in significantly higher prestimulus frontocentral theta and alpha activity. CONCLUSIONS: These findings suggest that out-of-phase theta tACS potently modulates top-down inhibitory control, supporting the feasibility of phase-lagged tACS to enhance inhibitory control performance.

Non-invasive electrical brain stimulation modulates human conscious perception of mental representation.

Mental representation is a key concept in cognitive science; nevertheless, its neural foundations remain elusive. We employed non-invasive electrical brain stimulation and functional magnetic resonance imaging to address this. During this process, participants perceived flickering red and green visual stimuli, discerning them either as distinct, non-fused colours or as a mentally generated, fused colour (orange). The application of transcranial alternating current stimulation to the medial prefrontal region (a key node of the default-mode network) suppressed haemodynamic activation in higher-order subthalamic and central executive networks associated with the perception of fused colours. This implies that higher-order thalamocortical and default-mode networks are crucial in humans' conscious perception of mental representation.

Sign Reversal of Spin-Transfer Torques.

Spin-transfer torque (STT) and spin-orbit torque (SOT) form the core of spintronics, allowing for the control of magnetization through electric currents. While the sign of SOT can be manipulated through material and structural engineering, it is conventionally understood that STT lacks a degree of freedom in its sign. However, this study presents the first demonstration of manipulating the STT sign by engineering heavy metals adjacent to magnetic materials in magnetic heterostructures. Spin torques are quantified through magnetic domain-wall speed measurements, and subsequently, both STT and SOT are systematically extracted from these measurements. The results unequivocally show that the sign of STT can be either positive or negative, depending on the materials adjacent to the magnetic layers. Specifically, Pd/Co/Pd films exhibit positive STT, while Pt/Co/Pt films manifest negative STT. First-principle calculations further confirm that the sign reversal of STT originates from the sign reversal of spin polarization of conduction electrons.

Extrinsic hydrophobicity-controlled silver nanoparticles as efficient and stable catalysts for CO2 electrolysis.

To realize economically feasible electrochemical CO2 conversion, achieving a high partial current density for value-added products is particularly vital. However, acceleration of the hydrogen evolution reaction due to cathode flooding in a high-current-density region makes this challenging. Herein, we find that partially ligand-derived Ag nanoparticles (Ag-NPs) could prevent electrolyte flooding while maintaining catalytic activity for CO2 electroreduction. This results in a high Faradaic efficiency for CO (>90%) and high partial current density (298.39 mA cm‒2), even under harsh stability test conditions (3.4 V). The suppressed splitting/detachment of Ag particles, due to the lipid ligand, enhance the uniform hydrophobicity retention of the Ag-NP electrode at high cathodic overpotentials and prevent flooding and current fluctuations. The mass transfer of gaseous CO2 is maintained in the catalytic region of several hundred nanometers, with the smooth formation of a triple phase boundary, which facilitate the occurrence of CO2RR instead of HER. We analyze catalyst degradation and cathode flooding during CO2 electrolysis through identical-location transmission electron microscopy and operando synchrotron-based X-ray computed tomography. This study develops an efficient strategy for designing active and durable electrocatalysts for CO2 electrolysis.

Out-of-phase transcranial alternating current stimulation modulates the neurodynamics of inhibitory control.

Transcranial alternating current stimulation (tACS) is an efficient neuromodulation technique that enhances cognitive function in a non-invasive manner. Using functional magnetic resonance imaging, we investigated whether tACS with different phase lags (0° and 180°) between the dorsal anterior cingulate and left dorsolateral prefrontal cortices modulated inhibitory control performance during the Stroop task. We found out-of-phase tACS mediated improvements in task performance, which was neurodynamically reflected as putamen, dorsolateral prefrontal, and primary motor cortical activation as well as prefrontal-based top-down functional connectivity. Our observations uncover the neurophysiological bases of tACS-phase-dependent neuromodulation and provide a feasible non-invasive approach to effectively modulate inhibitory control.

Long-term control of diabetes by tofacitinib-based immunosuppressive regimen after allo islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets.

Porcine islet xenotransplantation has been highlighted as an alternative to allo islet transplantation. Despite the remarkable progress that has been made in porcine-islet pre-clinical studies in nonhuman primates, immunological tolerance to porcine islets has not been achieved to date. Therefore, allo islet transplantation could be required after the failure of porcine islet xenotransplantation. Here, we report the long-term control of diabetes by allogeneic pancreatic islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets. Four diabetic male rhesus monkeys received the porcine islets and then allo islets (5700-19 000 IEQ/kg) were re-transplanted for a short or long period after the first xeno islet rejection. The recipient monkeys were treated with an immunosuppressive regimen consisting of ATG, humira, and anakinra for induction, and sirolimus and tofacitinib for maintenance therapy. The graft survival days of allo islets in these monkeys were >440, 395, >273, and 127, respectively, similar to that in allo islet transplanted cynomolgus monkeys that received the same immunosuppressive regimen without xeno sensitization. Taken together, it is likely that prior islet xenotransplantation does not affect the survival of subsequent allo islets under clinically applicable immunosuppressants.

Electroencephalographic features of elderly patients during anesthesia induction with remimazolam: a sub-study of a randomized controlled trial.

BACKGROUND: Although remimazolam is used as a general anesthetic in elderly patients due to its hemodynamic stability, the electroencephalogram (EEG) characteristics of remimazolam are not well-known. The purpose of this study was to identify the EEG features of remimazolam-induced unconsciousness in elderly patients and compare them with propofol. METHODS: Remimazolam (n=26) or propofol (n=26) were randomly administered for anesthesia induction in surgical patients. The hypnotic agent was blinded only to the patients. During the induction of anesthesia, remimazolam was administered at a rate of 6 mg/kg/h, and propofol was administered at a target effect-site concentration of 3.5 µg/ml. The EEG signals from 8 channels (Fp1,Fp2,Fz,F3,F4,Pz,P3,P4, referenced to A2, using the 10-20 system) were acquired during the induction of anesthesia and in the postoperative care unit. Power spectrum analysis was performed, and directed functional connectivity between frontal and parietal regions was evaluated using normalized symbolic transfer entropy. Functional connectivity in unconscious processes induced by remimazolam or propofol was compared with baseline. To compare each power of frequency over time of the two hypnotic agents, a permutation test with t statistic was conducted. RESULTS: Compared to the baseline in the alpha band, the feedback connectivity decreased by an average of 46% and 43%, respectively, after the loss of consciousness induced by remimazolam and propofol (95% CI for the mean difference:-0.073 to -0.044 for remimazolam, P<0.001,-0.068 to -0.042 for propofol,P<0.001). Asymmetry in the feedback and feedforward connectivity in the alpha band was suppressed after the loss of consciousness induced by remimazolam and propofol. There were no significant differences in the power of each frequency over time between the two hypnotic agents (minimum q-value=0.4235). CONCLUSIONS: Both regimens showed a greater decrease in feedback connectivity compared to a decrease in feedforward connectivity after loss of consciousness, leading to a disruption of asymmetry between the frontoparietal connectivity.

Exosomes Secreted During Myogenic Differentiation of Human Fetal Cartilage-Derived Progenitor Cells Promote Skeletal Muscle Regeneration through miR-145-5p.

BACKGROUND: Currently, there is no apparent treatment for sarcopenia, which is characterized by diminished myoblast function. We aimed to manufacture exosomes that retain the myogenic differentiation capacity of human fetal cartilage-derived progenitor cells (hFCPCs) and investigate their muscle regenerative efficacy in myoblasts and a sarcopenia rat model. METHODS: The muscle regeneration potential of exosomes (F-Exo) secreted during myogenic differentiation of hFCPCs was compared to human bone marrow mesenchymal stem cells-derived (hBMSCs) exosomes (B-Exo) in myoblasts and sarcopenia rat model. The effect of F-Exo was analyzed through known microRNAs (miRNAs) analysis. The mechanism of action of F-Exo was confirmed by measuring the expression of proteins involved in the Wnt signaling pathway. RESULTS: F-Exo and B-Exo showed similar exosome characteristics. However, F-Exo induced the expression of muscle markers (MyoD, MyoG, and MyHC) and myotube formation in myoblasts more effectively than B-Exo. Moreover, F-Exo induced greater increases in muscle fiber cross-sectional area and muscle mass compared to B-Exo in a sarcopenia rat. The miR-145-5p, relevant to muscle regeneration, was found in high concentrations in the F-Exo, and RNase pretreatment reduced the efficacy of exosomes. The effects of F-Exo on the expression of myogenic markers in myoblasts were paralleled by the miR-145-5p mimics, while the inhibitor partially negated this effect. F-Exo was involved in the Wnt signaling pathway by enhancing the expression of Wnt5a and ß-catenin. CONCLUSION: F-Exo improved muscle regeneration by activating the Wnt signaling pathway via abundant miR-145-5p, mimicking the remarkable myogenic differentiation potential of hFCPCs.

Fixed-Bearing Unicompartmental Knee Arthroplasty in Tibia Vara Knees Results in Joint Surface Malalignment and Varus Joint Line Obliquity, but Does Not Affect Functional Outcomes at Greater Than 5 Years Follow-Up.

BACKGROUND: This study aimed to investigate the clinical outcomes of fixed-bearing medial unicompartmental knee arthroplasty (UKA) for tibia vara knees and the associated changes in joint space malalignment (JSM) and joint line obliquity (JLO). METHODS: We retrospectively analyzed a consecutive group of 100 patients who underwent fixed-bearing medial UKA with a preoperative medial proximal tibia angle (MPTA) ≥86° (n = 50) and MPTA <86° (n = 50) and who had a minimum 5-year follow-up. Radiological parameters, including the hip-knee-ankle angle, MPTA, and the postoperative JSM and JLO, were measured. Functional evaluation was performed using the range of motion, visual analog scale, Knee Society Knee Score, Knee Society Function Score, and Western Ontario and McMaster Universities Osteoarthritis Index score. RESULTS: The MPTA <86° group showed significantly higher postoperative JLO (91.8 versus 90.4°, respectively; P = .002) and JSM (6.1 versus 4.2°, respectively; P = .026) compared to the MPTA ≥86° group. Functional outcomes, including range of motion, visual analog scale, Knee Society Knee Score, Knee Society Function Score, and Western Ontario and McMaster Universities Osteoarthritis Index scores, were not significantly different between the 2 groups. CONCLUSIONS: Fixed-bearing medial UKA is a safe and effective surgical option for patients who have tibia vara knees, as an increase in JLO and JSM postoperatively does not have a clinically relevant impact, even after a minimum 5-year follow-up.

Synovium-Derived Mesenchymal Stem Cell-Based Scaffold-Free Fibrocartilage Engineering for Bone-Tendon Interface Healing in an Anterior Cruciate Ligament Reconstruction Model.

BACKGROUND: Current tendon and ligament reconstruction surgeries rely on scar tissue healing which differs from native bone-to-tendon interface (BTI) tissue. We aimed to engineer Synovium-derived mesenchymal stem cells (Sy-MSCs) based scaffold-free fibrocartilage constructs and investigate in vivo bone-tendon interface (BTI) healing efficacy in a rat anterior cruciate ligament (ACL) reconstruction model. METHODS: Sy-MSCs were isolated from knee joint of rats. Scaffold-free sy-MSC constructs were fabricated and cultured in differentiation media including  TGF-ß-only, CTGF-only, and TGF-ß + CTGF. Collagenase treatment on tendon grafts was optimized to improve cell-to-graft integration. The effects of fibrocartilage differentiation and collagenase treatment on BTI integration was assessed by conducting histological staining, cell adhesion assay, and tensile testing. Finally, histological and biomechanical analyses were used to evaluate in vivo efficacy of fibrocartilage construct in a rat ACL reconstruction model. RESULTS: Fibrocartilage-like features were observed with in the scaffold-free sy-MSC constructs when applying TGF-ß and CTGF concurrently. Fifteen minutes collagenase treatment increased cellular attachment 1.9-fold compared to the Control group without affecting tensile strength. The failure stress was highest in the Col + D + group (22.494 ± 13.74 Kpa) compared to other groups at integration analysis in vitro. The ACL Recon + FC group exhibited a significant 88% increase in estimated stiffness (p = 0.0102) compared to the ACL Recon group at the 4-week postoperative period. CONCLUSION: Scaffold-free, fibrocartilage engineering together with tendon collagenase treatment enhanced fibrocartilaginous BTI healing in ACL reconstruction.

Resting-state electroencephalographic characteristics related to mild cognitive impairments.

Alzheimer's disease (AD) causes a rapid deterioration in cognitive and physical functions, including problem-solving, memory, language, and daily activities. Mild cognitive impairment (MCI) is considered a risk factor for AD, and early diagnosis and treatment of MCI may help slow the progression of AD. Electroencephalography (EEG) analysis has become an increasingly popular tool for developing biomarkers for MCI and AD diagnosis. Compared with healthy elderly, patients with AD showed very clear differences in EEG patterns, but it is inconclusive for MCI. This study aimed to investigate the resting-state EEG features of individuals with MCI (n = 12) and cognitively healthy controls (HC) (n = 13) with their eyes closed. EEG data were analyzed using spectral power, complexity, functional connectivity, and graph analysis. The results revealed no significant difference in EEG spectral power between the HC and MCI groups. However, we observed significant changes in brain complexity and networks in individuals with MCI compared with HC. Patients with MCI exhibited lower complexity in the middle temporal lobe, lower global efficiency in theta and alpha bands, higher local efficiency in the beta band, lower nodal efficiency in the frontal theta band, and less small-world network topology compared to the HC group. These observed differences may be related to underlying neuropathological alterations associated with MCI progression. The findings highlight the potential of network analysis as a promising tool for the diagnosis of MCI.

Observation of the orbital Hall effect in a light metal Ti.

The orbital Hall effect1 refers to the generation of electron orbital angular momentum flow transverse to an external electric field. Contrary to the common belief that the orbital angular momentum is quenched in solids, theoretical studies2,3 predict that the orbital Hall effect can be strong and is a fundamental origin of the spin Hall effect4-7 in many transition metals. Despite the growing circumstantial evidence8-11, its direct detection remains elusive. Here we report the magneto-optical observation of the orbital Hall effect in the light metal titanium (Ti). The Kerr rotation by the orbital magnetic moment accumulated at Ti surfaces owing to the orbital Hall current is measured, and the result agrees with theoretical calculations semi-quantitatively and is supported by the orbital torque12 measurement in Ti-based magnetic heterostructures. This result confirms the orbital Hall effect and indicates that the orbital angular momentum is an important dynamic degree of freedom in solids. Moreover, this calls for renewed studies of the orbital effect on other degrees of freedom such as spin2,3,13,14, valley15,16, phonon17-19 and magnon20,21 dynamics.

Enhanced Operational Characteristics Attained by Applying HfO2 as Passivation in AlGaN/GaN High-Electron-Mobility Transistors: A Simulation Study.

This study investigates the operating characteristics of AlGaN/GaN high-electron-mobility transistors (HEMTs) by applying HfO2 as the passivation layer. Before analyzing HEMTs with various passivation structures, modeling parameters were derived from the measured data of fabricated HEMT with Si3N4 passivation to ensure the reliability of the simulation. Subsequently, we proposed new structures by dividing the single Si3N4 passivation into a bilayer (first and second) and applying HfO2 to the bilayer and first passivation layer only. Ultimately, we analyzed and compared the operational characteristics of the HEMTs considering the basic Si3N4, only HfO2, and HfO2/Si3N4 (hybrid) as passivation layers. The breakdown voltage of the AlGaN/GaN HEMT having only HfO2 passivation was improved by up to 19%, compared to the basic Si3N4 passivation structure, but the frequency characteristics deteriorated. In order to compensate for the degraded RF characteristics, we modified the second Si3N4 passivation thickness of the hybrid passivation structure from 150 nm to 450 nm. We confirmed that the hybrid passivation structure with 350-nm-thick second Si3N4 passivation not only improves the breakdown voltage by 15% but also secures RF performance. Consequently, Johnson's figure-of-merit, which is commonly used to judge RF performance, was improved by up to 5% compared to the basic Si3N4 passivation structure.

Lateral Retinacular Release During Medial Unicompartmental Knee Arthroplasty in the Presence of Patello-Femoral Joint Arthritis Relieves Patello-Femoral Joint Pressure and Improves Associated Symptoms.

BACKGROUND: This study evaluated the effects of concomitant lateral patellar retinacular release (LPRR) during medial unicompartmental knee arthroplasty (UKA). METHODS: We retrospectively analyzed 100 patients who had patello-femoral joint (PFJ) arthritis who underwent medial UKA with (n = 50) and without (n = 50) LPRR who had ≥2 years follow-up. Radiological parameters associated with lateral retinacular tightness, including patellar tilt angle (PTA), lateral patello-femoral angle (LPFA), and congruence angle, were measured. Functional evaluation was performed using the Knee Society Pain Score, Knee Society Function Score (KSFS), Kujala Score, and the Western Ontario McMaster Universities Osteoarthritis Index score. Intraoperative patello-femoral pressure evaluation was performed on 10 knees to evaluate the pressure changes before and after LPRR. Mann-Whitney U-tests were used for statistical analyses. RESULTS: Demographic data did not differ between the LPRR(+) and LPRR(-) groups. A decrease in PTA and an increase in LPFA were observed in the LPRR(+) group compared to those in the LPRR(-) group (PTA; -0.54 versus -1.74, P = .002, LPFA; 0.51 versus 2.01, P = .010). The LPRR(+) group showed significantly better KSFS and Kujala scores than the LPRR(-) group (KSFS: 90 versus 80, P = .017; Kujala score: 86 versus 79, P = .009). Intraoperative patello-femoral pressure analysis showed a 22.6% reduction in the PFJ contact pressure and an 18.7% reduction in PFJ peak pressure after LPRR. (P = .0015, P < .0001, respectively) CONCLUSION: A LPRR during UKA may be a simple and useful adjunct procedure to relieve PFJ symptoms with concomitant PFJOA.

Effects of glycosaminoglycan content in extracellular matrix of donor cartilage on the functional properties of osteochondral allografts evaluated by micro-CT non-destructive analysis.

Osteochondral allograft (OCA) is an important surgical procedure used to repair extensive articular cartilage damage. It is known that chondrocyte viability is crucial for maintaining the biochemical and biomechanical properties of OCA, which is directly related to the clinical success of the operation and is the only standard for preoperative evaluation of OCA. However, there is a lack of systematic research on the effect of the content of cellular matrix in OCA cartilage tissue on the efficacy of transplantation. Therefore, we evaluated the effect of different GAG contents on the success of OCA transplantation in a rabbit animal model. Each rabbit OCA was treated with chondroitinase to regulate glycosaminoglycan (GAG) content in the tissue. Due to the different action times of chondroitinase, they were divided into 4 experimental groups (including control group, 2h, 4h, and 8h groups). The treated OCAs of each group were used for transplantation. In this study, transplant surgery effects were assessed using micro-computed tomography (µCT) and histological analysis. Our results showed that tissue integration at the graft site was poorer in the 4h and 8h groups compared to the control group at 4 and 12 weeks in vivo, as were the compressive modulus, GAG content, and cell density reduced. In conclusion, we evaluated the biochemical composition of OCAs before and after surgery using µCT analysis and demonstrated that the GAG content of the graft decreased, it also decreased during implantation; this resulted in decreased chondrocyte viability after transplantation and ultimately affected the functional success of OCAs.

Potential of secretome of human fetal cartilage progenitor cells as disease modifying agent for osteoarthritis.

AIMS: Osteoarthritis (OA) is caused by an imbalance in the synthesis and degradation of cartilage tissue by chondrocytes. Therefore, a therapeutic agent for OA patients that can positively affect both synthesis and degradation is needed. However, current nonsurgical treatments for OA can barely achieve satisfactory long-term outcomes in cartilage repair. Human fetal cartilage progenitor cells-secretome (ShFCPC) has shown potent anti-inflammatory and tissue-repair effects; however, its underlying mechanisms and effects on OA have rarely been systematically elucidated. This study aims to analyze and evaluate the potency of ShFCPC in modifying OA process. MAIN METHODS: Herein, secreted proteins enriched in ShFCPC have been characterized, and their biological functions both in vitro and in vivo in an OA model are compared with those of human bone marrow-derived mesenchymal stem cells-secretome (ShBMSC) and hyaluronan (HA). KEY FINDINGS: Secretome analysis has shown that ShFCPC is significantly enriched with extracellular matrix molecules involved in many effects of cellular processes required for homeostasis during OA progression. Biological validation in vitro has shown that ShFCPC protects chondrocyte apoptosis by suppressing the expression of inflammatory mediators and matrix-degrading proteases and promotes the secretion of pro-chondrogenic cytokines in lipopolysaccharide-induced coculture of human chondrocytes and SW982 synovial cells compared with ShBMSC. Moreover, in a rat OA model, ShFCPC protects articular cartilage by reducing inflammatory cell infiltration and M1/M2 macrophage ratio in the synovium, which directly contributes to an increase in immunomodulatory atmosphere and enhances cartilage repair compared to ShBMSC and HA. SIGNIFICANCE: Our findings support clinical translations of ShFCPC as a novel agent for modifying OA process.

Deep learning-based electroencephalic diagnosis of tinnitus symptom.

Tinnitus is a neuropathological phenomenon caused by the recognition of external sound that does not actually exist. Existing diagnostic methods for tinnitus are rather subjective and complicated medical examination procedures. The present study aimed to diagnose tinnitus using deep learning analysis of electroencephalographic (EEG) signals while patients performed auditory cognitive tasks. We found that, during an active oddball task, patients with tinnitus could be identified with an area under the curve of 0.886 through a deep learning model (EEGNet) using EEG signals. Furthermore, using broadband (0.5 to 50 Hz) EEG signals, an analysis of the EEGNet convolutional kernel feature maps revealed that alpha activity might play a crucial role in identifying patients with tinnitus. A subsequent time-frequency analysis of the EEG signals indicated that the tinnitus group had significantly reduced pre-stimulus alpha activity compared with the healthy group. These differences were observed in both the active and passive oddball tasks. Only the target stimuli during the active oddball task yielded significantly higher evoked theta activity in the healthy group compared with the tinnitus group. Our findings suggest that task-relevant EEG features can be considered as a neural signature of tinnitus symptoms and support the feasibility of EEG-based deep-learning approach for the diagnosis of tinnitus.

Development and In Vivo Assessment of an Injectable Cross-Linked Cartilage Acellular Matrix-PEG Hydrogel Scaffold Derived from Porcine Cartilage for Tissue Engineering.

The cartilage acellular matrix (CAM) derived from porcine cartilage, which does not induce significant inflammation and provides an environment conducive for cell growth and differentiation, is a promising biomaterial candidate for scaffold fabrication. However, the CAM has a short period in vivo, and the in vivo maintenance is not controlled. Therefore, this study is aimed at developing an injectable hydrogel scaffold using a CAM. The CAM is cross-linked with a biocompatible polyethylene glycol (PEG) cross-linker to replace typically used glutaraldehyde (GA) cross-linker. The cross-linking degree of cross-linked CAM by PEG cross-linker (Cx-CAM-PEG) according to the ratios of the CAM and PEG cross-linker is confirmed by contact angle and heat capacities measured by differential scanning calorimetry. The injectable Cx-CAM-PEG suspension exhibits controllable rheological properties and injectability. Additionally, injectable Cx-CAM-PEG suspensions with no free aldehyde group are formed in the in vivo hydrogel scaffold almost simultaneously with injection. In vivo maintenance of Cx-CAM-PEG is realized by the cross-linking ratio. The in vivo formed Cx-CAM-PEG hydrogel scaffold exhibits certain host-cell infiltration and negligible inflammation within and near the transplanted Cx-CAM-PEG hydrogel scaffold. These results suggest that injectable Cx-CAM-PEG suspensions, which are safe and biocompatible in vivo, represent potential candidates for (pre-)clinical scaffolds.