Histological characterization of pulp regeneration using decellularized human dental pulp and mesenchymal stem cells in a feline model.

Regenerative endodontics aims to restore pulp tissues, thus preserving the vitality of the tooth. One promising approach involves the utilization of decellularized human dental pulp (DHDP) as a scaffold repopulated with Wharton's Jelly mesenchymal stem cells (WJMSCs). This study aimed to regenerate pulp tissues using DHDP and WJMSCs following pulpectomy in mature canine teeth of a feline animal model and to investigate the histological features of the regenerated pulp. A 12-month-old male domestic shorthaired felines were used as subjects. Teeth were categorized into untreated (Group 1), pulpectomy with mineral trioxide aggregate (MTA) (Group 2), and pulpectomy with DHDP-repopulated scaffold and MTA (Group 3). The animals were sacrificed six weeks post-intervention. H&E and immunohistochemistry using anti-collagen type 1 and laminin antibodies were used to stain the tissue sections. Histological examinations presented pulp-like tissues in Group 3, with tissue components similar to the structures found in Group 1. Immunohistochemical analysis demonstrated the presence of collagen type I and laminin within the regenerated tissues. The root canals of teeth in Group 2 were devoid of pulpal tissue. DHDP with WJMSCs can potentially be used for pulp regeneration, supporting the modality for developing new clinical protocols in stem cell therapy.

Production and physico-chemical characterization of nano-sized collagen from equine tendon.

In recent years, significant academic and commercial interest has focused on collagen derived from horse tendons, with potential applications across diverse sectors such as medicine, pharmaceuticals, and cosmetics. Nano collagen, with its enhanced wound penetration, improved cell contact, and heightened cellular regeneration and repair capabilities due to its high surface area, holds promise for a wide range of applications. In this study, we present a novel method for producing nano collagen from the equine tendon. Our approach is characterized by its speed, affordability, simplicity and environmentally friendly nature, with precise temperature-control to prevent collagen denaturation. We conducted a comprehensive characterization of the obtained samples, including assessments of morphology, chemical and thermal properties, particle size distribution and biocompatibility. Importantly, our results indicate improvements in thermal stability, and surface roughness of nano collagen, while preserving its molecular weight. These advancements expand the potential applications of nano collagen in various fields.

Engineering a durable BDDE cross-linked collagen filler for skin rejuvenation.

Skin aging, characterized by reduced regeneration, chronic inflammation, and heightened skin cancer risk, poses a significant challenge. Collagen fillers have emerged as a potential solution for skin rejuvenation by stimulating collagen regeneration. However, their clinical efficacy is limited by inherent instability and vulnerability toin vivodegradation by collagenase. Chemical cross-linking presents a promising approach to enhance stability, but it carries risks such as cytotoxicity, calcification, and discoloration. Here, we introduce a highly durable 1,4-butanediol diglycidyl ether (BDDE) cross-linked collagen filler for skin rejuvenation. BDDE effectively cross-links collagen, resulting in fillers with exceptional mechanical strength and injectability. These fillers demonstrate favorable stability and durability, promoting proliferation, adhesion, and spreading of human foreskin fibroblast-1 cellsin vitro. In vivostudies confirm enhanced collagen regeneration without inducing calcification. BDDE cross-linked collagen fillers offer promising prospects for medical cosmetology and tissue regeneration.

Recombinant Humanized Collagen Type XVII Promotes Oral Ulcer Healing via Anti-Inflammation and Accelerate Tissue Healing.

Introduction: Recombinant humanized collagen, as a novel biomaterial, exhibits multiple excellent biological functions, such as inhibition of inflammation, promotion of cell proliferation and vascular proliferation, and promotion of tissue healing. However, there is a lack of conclusive evidence regarding the specific role of recombinant humanized collagen type 17 (rhCol 17) in oral ulcer healing. This study explored whether rhCol 17 could promote the proliferation of human gingival fibroblasts (HGFs) and inhibit its inflammation, and whether it could promote the healing of oral ulcers in rats by inhibiting inflammation and accelerating tissue healing. Methods: At the cellular level, we investigated the effect of rhCol 17 on the proliferation of (HGFs) by CCK8; HGFs were mixed with lipopolysaccharide (LPS) to investigate the effect of rhCol 17 on HGFs in an inflammatory state. Eighteen adult male Sprague-Dawley rats were randomly distributed into three groups: blank control group, carbomer group (carbomer sprayed only), and rhCol 17 group (carbomer containing rhCol 17 sprayed), 1 time/day. The samples were collected at D3 and D5. At completion, histological staining and PCR were carried out to study its effect on the healing of oral ulcers in rats. Results: Through cellular experiments, we found that rhCol 17 possesses good biocompatibility and anti-inflammatory properties, and can effectively promote the proliferation and migration of HGFs, as well as significantly reduce the inflammation level of the cells. The animal experimental results showed that rhCol 17 could significantly reduce the inflammation level, promote collagen deposition and angiogenesis at the ulcer site, thus effectively accelerating the healing of oral ulcers in rats. Conclusion: In summary, the collagen sprays containing rhCol 17 have excellent anti-inflammatory effects and could accelerate tissue healing and are expected to provide a new effective treatment for patients with recurrent oral ulcers.

Scurvy: A Rare Disease or a Rare Diagnosis?

Introduction: Scurvy, the disease state caused by ascorbic acid deficiency, was once an extremely common disease but is now thought to be a rare disease in postmodern societies. Physicians are not trained to consider scurvy as a possible diagnosis in patients at risk; rather, it is considered a rare diagnosis to add to a differential for completeness's sake. Methods: We sought to describe the scorbutic patients seen by one physician during a busy academic emergency medicine career. Case series of patients seen by one physician between 1993 and 2023 at five academic teaching hospitals with Emergency Departments (EDs) in the mid-Eastern United States. Presenting signs and symptoms, known scurvy risk factors, Vitamin C levels, clinical course, and outcome for each patient are described. Results: There were 14 presentations by 12 patients diagnosed with scurvy who were initially evaluated in the ED between 1993 and 2023. Each patient had a known risk factor for inadequate Vitamin C intake. All had clinical findings suggestive of scurvy and all but one had a subnormal serum Vitamin C level detected on serum samples sent from the ED. Conclusion: The detection of 12 cases of scurvy by one physician over a three-decade period highlights the importance of screening for scurvy in at-risk populations and generates the hypothesis that scurvy is not a rare disease but rather a rare diagnosis. This research hypothesis should be investigated in further studies.

Predictors of Long-term Patient-Reported Outcome Measures After Collagen Meniscal Implant for Partial Meniscal Defects.

Background: Collagen meniscal implant (CMI) is considered an effective procedure for reducing knee pain and improving knee function after previous meniscectomy. Nevertheless, the current knowledge regarding long-term patient reported-outcome measures after CMI is limited. Purpose: To evaluate clinical outcomes, reoperations, and failures of CMI at a minimum 10-year follow-up. Study Design: Case series; Level of evidence, 4. Methods: Consecutive patients who underwent CMI at a single institution were screened for eligibility. Inclusion criteria for the present study were (1) medial or lateral CMI; (2) isolated or combined procedure with anterior cruciate ligament reconstruction, knee osteotomy, or cartilage treatment; and (3) follow-up between 10 and 15 years. Demographics and surgical details were obtained via chart review. Patients were asked if they were satisfied with the procedure and were evaluated with the Lysholm score, Knee injury and Osteoarthritis Outcome Score (KOOS), visual analog scale for pain, and Tegner score at the final follow-up. Cases requiring partial or total scaffold removal for any reason (including scaffold breakage, infection, or surgery for osteoarthritis progression) were considered surgical failure. Survival analysis was performed with Kaplan-Meier curve, and clinical scores were analyzed based on the Patient Acceptable Symptom State (PASS). Results: A total of 92 patients (mean age, 42.2 years were included in the analysis. A significant improvement in all clinical scores was reported between the preoperative evaluation and the last follow-up. A chondropathy with Outerbridge grade ≥3 was associated with significantly overall lower clinical scores, while a timing from meniscectomy to CMI of ≥5 years determined more pain at rest and reduced Quality of Life in the KOOS subscale. No significant difference was found in terms of clinical scores between patients undergoing isolated and combined procedures. At the final follow-up, the mean Lysholm score was 76.3 points. In total, 12 cases (13%) were considered surgical failures. Sixteen patients (17%) did not reach PASS for the Lysholm score, with a total of 28 cases (30%) classified as clinical failures. Overall, 19% (KOOS Pain) and 40% (KOOS Symptoms) of patients did not achieve the PASS in the KOOS subscales. Chondropathy with Outerbridge grade ≥3 was associated with a higher risk of not achieving the PASS in all the KOOS subscales, while age at surgery of ≥45 years resulted in a lower risk of not achieving PASS in the Pain subscale. At the last follow-up, 63% of patients were still involved in sports activity, with 41% at the same or higher level. Finally, 80% of the patients were satisfied with the procedure. Conclusion: Up to 10 years after surgery, around 70% of the patients who underwent CMI reported satisfactory clinical results, with clinical subjective scores still higher compared with the preoperative evaluation. Overall, 30% of cases were considered clinical failures, with 13% considered surgical failures and 17% not meeting the PASS for the Lysholm score. In addition, cartilage status and time from meniscectomy were shown to have a negative impact on the outcomes, while an age ≥45 years was associated with less pain. There was no clinical difference between patients who underwent isolated CMI or combined procedures.

Reconstructing dietary practices at Tell Kamid el-Loz (Lebanon) during the Bronze and Iron Age III / Persian to Hellenistic periods using plant micro-remains from dental calculus and stable isotope analysis of bone collagen.

Tell Kamid el-Loz (Lebanon) was an important Bronze Age urban center that dominated one of the central crossroads of the Ancient Near East, connecting Egypt and the Levant with northern Mesopotamia, Anatolia, and Syria, as well as the interior with the Mediterranean coast. However, by the early Iron Age, the site had shrunk to a small rural settlement. Later, in the Iron Age III / Persian-Hellenistic, only enigmatic pits and a large cemetery remained. In this paper, we analyzed plant micro-remains from the dental calculus of 15 individuals (3 from the Middle Bronze Age II and 12 from the Iron Age III / Persian-Hellenistic) and δ 13C and δ 15N stable isotope data from tbulk bone collagen of 74 individuals (10 from the Middle Bronze Age II and 64 from the Iron Age III / Persian-Hellenistic) and 13 Late Bronze Age animal bones (7 Ovis/Capra and 6 Bos). Our results indicate general stability of human diet throughout the Middle Bronze Age II and the Iron III / Persian-Hellenistic periods, with a reliance on C3 plant crops and terrestrial animals also consuming C3 plants. In the later period, the plant micro-remains indicate the consumption of C4 plants and sedges, and the stable isotope analysis indicates differences in diet between males and females. Supplementary Information: The online version contains supplementary material available at 10.1007/s12520-024-02000-w.

Quantified planar collagen distribution in healthy and degenerative mitral valve: biomechanical and clinical implications.

Degenerative mitral valve disease is a common valvular disease with two arguably distinct phenotypes: fibroelastic deficiency and Barlow's disease. These phenotypes significantly alter the microstructures of the leaflets, particularly the collagen fibers, which are the main mechanical load carriers. The predominant method of investigation is histological sections. However, the sections are cut transmurally and provide a lateral view of the microstructure of the leaflet, while the mechanics and function are determined by the planar arrangement of the collagen fibers. This study, for the first time, quantitatively examined planar collagen distribution quantitatively in health and disease using second harmonic generation microscopy throughout the thickness of the mitral valve leaflets. Twenty diseased samples from eighteen patients and six control samples were included in this study. Healthy tissue had highly aligned collagen fibers. In fibroelastic deficiency they are less aligned and in Barlow's disease they are completely dispersed. In both diseases, collagen fibers have two preferred orientations, which, in contrast to the almost constant one orientation in healthy tissues, also vary across the thickness. The results indicate altered in vivo mechanical stresses and strains on the mitral valve leaflets as a result of disease-related collagen remodeling, which in turn triggers further remodeling.

Anti-proliferative impact of resveratrol on gingival fibroblasts from juvenile hyaline fibromatosis.

AIM: Resveratrol is a natural polyphenolic compound with biological activities such as anti-inflammation and antioxidation. Its anti-fibrotic effect has been experimentally demonstrated in the pancreas and liver. This study aims to determine the anti-proliferative effect of resveratrol on fibroblasts obtained from hyperplastic gingival tissues from a patient diagnosed with Juvenile Hyaline Fibromatosis (JHF). MATERIALS AND METHODS: Primary gingival fibroblast cell lines were obtained from gingival growth tissues by the gingivectomy of a patient with JHF. Gingival fibroblasts were treated with or without 3 different doses of resveratrol (50, 100, 200 µM). Cytotoxicity and cell proliferation were evaluated after 24, 48, and 72 h. Collagen, TGF, and CTGF were analyzed by ELISA in the 48-hour supernatants. RESULTS: All three doses of resveratrol suppressed the proliferation of JHF gingival fibroblasts at 24 and 48 h without showing any cytotoxic effect compared to the control group (p < 0.0001). At 72 h, 100 and 200 µM resveratrol showed significantly less proliferation (p < 0.0001), less collagen, CTGF, and TGF- ß (p < 0.001) than the control group. CONCLUSION: Resveratrol had a profound anti-proliferative effect on gingival fibroblasts obtained from gingival enlargements with JHF, suggesting that it can be used as a therapeutic to prevent excessive cell growth by suppressing collagen, CTGF, and TGF- ß synthesis in the pathogenesis of hyperplasia.

In Vivo Photoacoustic Ultrasound (PAUS) Assay for Monitoring Tendon Collagen Compositional Changes during Injury and Healing.

Tendon injury and healing involve significant changes to tissue biology and composition. Current techniques often require animal sacrifice or tissue destruction, limiting assessment of dynamic changes in tendons, including treatment response, disease development, rupture risk, and healing progression. Changes in tendon composition, such as altered collagen content, can significantly impact tendon mechanics and function. Analyses of compositional changes typically require ex vivo techniques with animal sacrifice or destruction of the tissue. In vivo evaluation of tendons is critical for longitudinal assessment. We hypothesize that photoacoustic ultrasound detects differences in collagen concentration throughout healing. We utilized photoacoustic ultrasound, a hybrid imaging modality that combines ultrasound and laser-induced photoacoustic signals to create detailed and high-resolution images of tendons, to identify its endogenous collagen composition. We correlated the photoacoustic signal to picrosirius red staining. The results show that the photoacoustic ultrasound-estimated collagen content in tendons correlates well with picrosirius red staining. This study demonstrates that photoacoustic ultrasound can assess injury-induced compositional changes within tendons and is the first study to image these targets in rat Achilles tendon in vivo.

Alveolar Ridge Preservation Using a Novel Species-Specific Collagen-Enriched Deproteinized Bovine Bone Mineral: Histological Evaluation of a Prospective Case Series.

In recent years, the significance of maintaining the alveolar ridge following tooth extractions has markedly increased. Alveolar ridge preservation (ARP) is a commonly utilized technique and a variety of bone substitute materials and biologics are applied in different combinations. For this purpose, a histological evaluation and the clinical necessity of subsequent guided bone regeneration (GBR) in delayed implantations were investigated in a prospective case series after ARP with a novel deproteinized bovine bone material (95%) in combination with a species-specific collagen (5%) (C-DBBM). Notably, block-form bone substitutes without porcine collagen are limited, and moreover, the availability of histological data on this material remains limited. Ten patients, each scheduled for tooth extraction and desiring future implantation, were included in this study. Following tooth extraction, ARP was performed using a block form of C-DBBM in conjunction with a double-folded bovine cross-linked collagen membrane (xCM). This membrane was openly exposed to the oral cavity and secured using a crisscross suture. After a healing period ranging from 130 to 319 days, guided trephine drilling was performed for implant insertion utilizing static computer-aided implant surgery (s-CAIS). Cores harvested from the area previously treated with ARP were histologically processed and examined. Guided bone regeneration (GBR) was not necessary for any of the implantations. Histological examination revealed the development of a lattice of cancellous bone trabeculae through appositional membranous osteogenesis at various stages surrounding C-DBBM granules as well as larger spongy or compact ossicles with minimal remnants. The clinical follow-up period ranged from 2.5 to 4.5 years, during which no biological or technical complications occurred. Within the limitations of this prospective case series, it can be concluded that ARP using this novel C-DBBM in combination with a bovine xCM could be a treatment option to avoid the need for subsequent GBR in delayed implantations with the opportunity of a bovine species-specific biomaterial chain.

Vitamin E Regulates the Collagen Contents in the Body Wall of Sea Cucumber (Apostichopus japonicus) via Its Antioxidant Effects and the TGF-ß/Smads Pathway.

A 70-day feeding experiment was performed to investigate the effects of dietary vitamin E at different addition levels (0, 100, 200, and 400 mg/kg) on the growth, collagen content, antioxidant capacity, and expressions of genes related to the transforming growth factor beta (TGF-ß)/Sma- and Mad-related protein (SMAD) signaling pathway in sea cucumbers (Apostichopus japonicus). The results showed that the A. japonicus in the group with 200 mg/kg vitamin E exhibited significantly higher growth rates, hydroxyproline (Hyp) and type III collagen contents, and superoxide dismutase (SOD) activity, as well as the upregulation of genes related to Tenascin, SMAD1, and TGF-ß. Additionally, the A. japonicus in the group with 100 mg/kg vitamin E exhibited significantly higher body-wall indexes, denser collagen arrangements, improved texture quality, higher activities of glutathione peroxidase (GSH-Px) and peroxidase (POD), as well as the upregulation of genes related to collagen type I alpha 2 chain (COL1A2), collagen type III alpha 1 chain (COL3A1), and Sp-Smad2/3 (SMAD2/3). In contrast, the A. japonicus in the group with 400 mg/kg vitamin E showed a decrease in the growth rates, reduced Hyp contents, increased type I collagen contents, collagen fiber aggregation and a harder texture, along with the downregulation of genes related to the TGF-ß/SMAD signaling pathway. Furthermore, the A. japonicus in the group with 400 mg/kg exhibited oxidative stress, reflected by the lower activities of SOD, GSH-Px, and POD. These results indicated that A. japonicus fed diets with the addition of 100-200 mg/kg vitamin E had improved collagen retention and texture quality by increasing the activities of antioxidant enzymes and the expressions of genes in the TGF-ß/SMAD signaling pathway. However, the excessive addition of vitamin E (400 mg/kg) induced oxidative stress, which could increase the collagen degradation and fibrosis and pose a threat to the growth and texture quality of A. japonicus.

TRAF1 Deficiency in Macrophages Drives Exacerbated Joint Inflammation in Rheumatoid Arthritis.

The tumor necrosis factor receptor-associated factor 1 (TRAF1) plays a key role in promoting lymphocyte survival, proliferation, and cytokine production. Recent evidence showed that TRAF1 plays opposing roles in monocytes and macrophages where it controls NF-κB activation and limits pro-inflammatory cytokine production as well as inflammasome-dependent IL-1ß secretion. Importantly, TRAF1 polymorphisms have been strongly linked to an increased risk of rheumatoid arthritis (RA). However, whether and how TRAF1 contributes to RA pathogenesis is not fully understood. Moreover, investigating the role of TRAF1 in driving RA pathogenesis is complicated by its multifaceted and opposing roles in various immune cells. In this study, we subjected wildtype (WT) mice to the collagen antibody-induced arthritis (CAIA) model of RA and injected them intra-articularly with WT- or TRAF1-deficient macrophages. We show that mice injected with TRAF1-deficient macrophages exhibited significantly exacerbated joint inflammation, immune cell infiltration, and tissue damage compared to mice injected with WT macrophages. This study may lay the groundwork for novel therapies for RA that target TRAF1 in macrophages.

Collagen-based hydrogels induce hyaline cartilage regeneration by immunomodulation and homeostasis maintenance.

Type I collagen (Col I) and hyaluronic acid (HA), derived from the extracellular matrix (ECM), have found widespread application in cartilage tissue engineering. Nevertheless, the potential of cell-free collagen-based scaffolds to induce in situ hyaline cartilage regeneration and the related mechanisms remain undisclosed. Here, we chose Col I and HA to construct Col I hydrogel and Col I-HA composite hydrogel with similar mechanical properties, denoted as Col and ColHA, respectively. Their potential to induce cartilage regeneration was investigated. The results revealed that collagen-based hydrogels could regenerate hyaline cartilage without any additional cells or growth factors. Notably, ColHA hydrogel stood out in this regard. It elicited a moderate activation, recruitment, and reprogramming of macrophages, thus efficiently mitigating local inflammation. Additionally, ColHA hydrogel enhanced stem cell recruitment, facilitated their chondrogenic differentiation, and inhibited chondrocyte fibrosis, hypertrophy, and catabolism, thereby preserving cartilage homeostasis. This study augments our comprehension of cartilage tissue induction theory by enriching immune-related mechanisms, offering innovative prospects for the design of cartilage defect repair scaffolds. STATEMENT OF SIGNIFICANCE: The limited self-regeneration ability of articular cartilage and post-injury inflammation poses significant challenges to its repair. Type I collagen (Col I) and hyaluronic acid (HA) are extensively used in cartilage tissue engineering. However, their specific roles in cartilage regeneration remain poorly understood. This study aimed to elucidate the functions of Col I and Col I-HA composite hydrogels (ColHA) in orchestrating inflammatory responses and promoting cartilage regeneration. ColHA effectively activated and recruited macrophages, reprogramming them from an M1 to an M2 phenotype, thus alleviating local inflammation. Additionally, ColHA facilitated stem cell homing, induced chondrogenesis, and concurrently inhibited fibrosis, hypertrophy, and catabolism, collectively contributing to the maintenance of cartilage homeostasis. These findings underscore the clinical potential of ColHA for repairing cartilage defects.

Effects on dentin nanomechanical properties, cell viability and dentin wettability of a novel plant-derived biomodification monomer.

OBJECTIVES: To evaluate the effects of dentin biomodification agents (Proanthocyanidin (PAC), Cardol (CD) and Cardol-methacrylate (CDMA) on dentin hydrophilicity by contact angle measurement, viability of dental pulp stem cells (DPSCs) and nanomechanical properties of the hybrid layer (HL). METHODS: CDMA monomer was synthesized from cardol through methacrylic acid esterification. Human extracted third molars were used for all experiments. For nanomechanical tests, specimens were divided in four groups according to the primer solutions (CD, CDMA, PAC and control) were applied before adhesive and composite coating. Nanomechanical properties of the HL were analyzed by nanoindentation test using a Berkovich probe in a nanoindenter. Wettability test was performed on dentin surfaces after 1 min biomodification and measured by contact angle analysis. Cytotoxicity was assessed by a MTT assay with DPSCs after 48 and 72 h. Data were analyzed with Student's t test or Two-way ANOVA and Tukey HSD test (p < 0.05). RESULTS: CD and CDMA solutions achieved greater hydrophobicity and increased the water-surface contact angles when compared to PAC and control groups (p < 0.05). PAC group showed a greater reduction of elastic modulus in nanoindentation experiments when compared to CD and CDMA groups (p < 0.05) after 4 months of aging. CD inhibited cell proliferation compared to all further materials (p < 0.05), whilst CDMA and PAC indicated no cell cytotoxicity to human DPSCs. SIGNIFICANCE: Cardol-methacrylate provided significantly higher hydrophobicity to dentin and demonstrated remarkable potential as collagen crosslinking, attaining the lowest decrease of HL's mechanical properties. Furthermore, such monomer did not affect pulp cytotoxicity, thereby highlighting promising feasibility for clinical applications.

Controlled Release of Ceria and Ferric Oxide Nanoparticles via Collagen Hydrogel for Enhanced Osteoarthritis Therapy.

Osteoarthritis (OA), characterized by chronic inflammation and cartilage degeneration, significantly affects over 500 million people globally. Nanoparticles have emerged as promising treatments for OA; however, current strategies often employ a single type of nanoparticle targeting specific disease stages, limiting sustained therapeutic efficacy. In this study, a novel collagen hydrogel is introduced, thiol crosslinked collagen-cerium oxide-poly(D,L-lactic-co-glycolic acid) microspheres encapsulating nanoparticles (CSH-CeO2-pFe2O3), designed for the controlled release of cerium oxide (CeO2) and ferric oxide (Fe2O3) nanoparticles for comprehensive OA management. The sulfhydryl cross-linked collagen matrix embeds CeO2 nanoparticles and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres encapsulating Fe2O3 nanoparticles. The CSH-CeO2-pFe2O3 hydrogel exhibits enhanced mechanical strength and remarkable injectability, along with a significant promotion of cell adhesion, proliferation, and chondrogenic differentiation. Notably, the hydrogel demonstrates intelligent responsiveness to high levels of reactive oxygen species, initiating the rapid release of CeO2 nanoparticles to address the intense inflammatory responses of early-stage OA, followed by the sustained release of Fe2O3 nanoparticles to facilitate cartilage regeneration during the proliferative phase. In a rat model with cartilage defects, the hydrogel significantly alleviates inflammation and enhances cartilage regeneration, holding substantial potential for effectively managing the pathologically complex OA.

Analysis of the Skin and Brain Transcriptome of Normally Pigmented and Pseudo-Albino Southern Flounder (Paralichthys lethostigma) Juveniles to Study the Molecular Mechanisms of Hypopigmentation and Its Implications for Species Survival in the Natural Environment.

Southern flounder skin pigmentation is a critical phenotypic characteristic for this species' survival in the natural environment. Normal pigmentation allows rapid changes of color for concealment to capture prey and UV light protection. In contrast, highly visible hypopigmented pseudo-albinos exhibit a compromised immune system and are vulnerable to predation, sensitive to UV exposure, and likely have poor survival in the wild. Skin and brain tissue samples from normally pigmented and hypopigmented individuals were analyzed with next-generation RNA sequencing. A total of 1,589,613 transcripts were used to identify 952,825 genes to assemble a de novo transcriptome, with 99.43% of genes mapped to the assembly. Differential gene expression and gene enrichment analysis of contrasting tissues and phenotypes revealed that pseudo-albino individuals appeared more susceptible to environmental stress, UV light exposure, hypoxia, and osmotic stress. The pseudo-albinos' restricted immune response showed upregulated genes linked to cancer development, signaling and response, skin tissue formation, regeneration, and healing. The data indicate that a modified skin collagen structure likely affects melanocyte differentiation and distribution, generating the pseudo-albino phenotype. In addition, the comparison of the brain transcriptome revealed changes in myelination and melanocyte stem cell activity, which may indicate modified brain function, reduced melanocyte migration, and impaired vision.

Wrinkle-Improving Effect of Novel Peptide That Binds to Nicotinic Acetylcholine Receptor.

Wrinkles, one of the most common signs of aging, are primarily caused by the continuous contraction of muscles. Muscle contraction is induced by the binding of acetylcholine (ACh), released at the neuromuscular junction, to nicotinic acetylcholine receptor (nAChR) present on the muscle cell surface. In this study, we aimed to develop a wrinkle-improving peptide that inhibits the binding of ACh to nAChR using peptide phage display technology. Our peptide showed a remarkably high binding affinity to nAChR subunit α1, with a value below 1 µM, and was found to inhibit the action of ACh through its interaction with these receptors. Furthermore, it increased collagen synthesis in skin cells and upregulated the expression of the aquaporin-3 (AQP3) and hyaluronan synthase-2 (HAS2) genes. These results confirm that the peptide effectively inhibits muscle contraction and enhances skin elasticity and hydration, contributing to its wrinkle-reducing effects. Clinical studies on humans observed significant improvement in wrinkles after three weeks of use, with substantial reduction observed after six weeks. In conclusion, these findings demonstrate the efficacy of the peptide (named Medipep) in reducing wrinkles.

The Biological Effect of Platelet-Rich Plasma on Rotator Cuff Tears: A Prospective Randomized In Vivo Study.

The positive effect of platelet-rich plasma (PRP) on tendon metabolism has been extensively investigated and proven in vitro. Additionally, in vivo animal studies have correlated the application of PRP with the enhancement of tenocyte anabolic activity in the setting of tendon degeneration. However, less is known about its in vivo effect on human tendon biology. The purpose of the current prospective randomized comparative study was to evaluate the effect of PRP on torn human supraspinatus tendon. Twenty consecutive eligible patients with painful and magnetic resonance imaging (MRI)-confirmed degenerative supraspinatus tendon tears were randomized in a one-to-one ratio into two groups. The patients in the experimental group (n = 10) underwent an ultrasound-guided autologous PRP injection in the subacromial space 6 weeks before the scheduled operation. In the control group (n = 10), no injection was made prior to surgery. Supraspinatus tendon specimens were harvested from the lateral end of the torn tendon during shoulder arthroscopy and were evaluated under optical and electron microscopy. In the control group, a mixed cell population of oval and rounded tenocytes within disorganized collagen and sites of accumulated inflammatory cells was detected. In contrast, the experimental group yielded abundant oval-shaped cells with multiple cytoplasmic processes within mainly parallel collagen fibers and less marked inflammation, simulating the intact tendon structure. These findings indicate that PRP can induce microscopic changes in the ruptured tendon by stimulating the healing process and can facilitate a more effective recovery.

Novel Collagen Membrane Formulations with Irinotecan or Minocycline for Potential Application in Brain Cancer.

Our study explores the development of collagen membranes with integrated minocycline or irinotecan, targeting applications in tissue engineering and drug delivery systems. Type I collagen, extracted from bovine skin using advanced fibril-forming technology, was crosslinked with glutaraldehyde to create membranes. These membranes incorporated minocycline, an antibiotic, or irinotecan, a chemotherapeutic agent, in various concentrations. The membranes, varying in drug concentration, were studied by water absorption and enzymatic degradation tests, demonstrating a degree of permeability. We emphasize the advantages of local drug delivery for treating high-grade gliomas, highlighting the targeted approach's efficacy in reducing systemic adverse effects and enhancing drug bioavailability at the tumor site. The utilization of collagen membranes is proposed as a viable method for local drug delivery. Irinotecan's mechanism, a topoisomerase I inhibitor, and minocycline's broad antibacterial spectrum and inhibition of glial cell-induced membrane degradation are discussed. We critically examine the challenges posed by the systemic administration of chemotherapeutic agents, mainly due to the blood-brain barrier's restrictive nature, advocating for local delivery methods as a more effective alternative for glioblastoma treatment. These local delivery strategies, including collagen membranes, are posited as significant advancements in enhancing therapeutic outcomes for glioblastoma patients.