Collagen Matrices Research Articles

Going for a Spin: Simultaneously Pulling and Spinning Microrods Speeds Transport through Collagen Matrices.

Magnetic drug targeting requires particles to move through the complex viscoelastic environments of tissues and biological fluids. However, these environments often inhibit particle motion, making it difficult for magnetically guided particles to reach their intended targets. Magnetic microrods are easy to grow and manipulate, but experience significant hindrance to transport in complex, tortuous, tissue-like environments. Simple magnetic force translation ("pulling" or "pushing") is often insufficient or inefficient for long-range transport of microrods through such environments. Designing microrods capable of rotating while being pulled with a magnetic force may enable rods to overcome hindrances to transport. We present microrods with orthogonally magnetized segments, actuated by simultaneous magnetic force and magnetic torque. By simultaneously pulling and rotating our rods we create smooth-surfaced magnetic drilling microrods (MDMRs) capable of enhanced motion through protein-dense biopolymers. We model magnetic force and torque on MDMRs, characterize MDMR dynamics during transport, and demonstrate enhanced MDMR transport through protein-dense matrices in vitro.

The impact of spatial structures of collagen on the hemostatic properties of collagen/calcium alginate composite membranes.

Biomacromolecule-based hemostatic materials with biocompatibility and biodegradability have become a topic of significant research for the treatment of wound hemorrhage. Among available biomacromolecules, collagen and alginate are particularly promising. Although collagen and alginate composite materials have been developed, the impact of the spatial structures of collagen on the hemostatic properties of these materials remains to be fully understood. Collagen fibers, formed through self-assembly, share the same composition as collagen but exhibit distinct spatial structures. In this study, calcium alginate (CaAlg) membranes containing collagen (Col) or collagen fibers (Col-fiber) were fabricated. By adjusting the ratio of collagen to alginate, Col/CaAlg and Col-fiber/CaAlg composite membranes with favourable tensile strength and water retention ability were selected. The impact of collagen's spatial structures on the structures and properties of composite membranes was investigated, revealing that collagen fibers enhance the cytocompatibility, blood compatibility, and hemostatic performance of alginate membranes more effectively than collagen. Therefore, the Col-fiber/CaAlg membranes could be a promising candidate for hemostatic applications.

Multifunctional DNA-Collagen Biomaterials: Developmental Advances and Biomedical Applications.

The complexation of nucleic acids and collagen forms a platform biomaterial greater than the sum of its parts. This union of biomacromolecules merges the extracellular matrix functionality of collagen with the designable bioactivity of nucleic acids, enabling advances in regenerative medicine, tissue engineering, gene delivery, and targeted therapy. This review traces the historical foundations and critical applications of DNA-collagen complexes and highlights their capabilities, demonstrating them as biocompatible, bioactive, and tunable platform materials. These complexes form structures across length scales, including nanoparticles, microfibers, and hydrogels, a process controlled by the relative amount of each component and the type of nucleic acid and collagen. The broad distribution of different types of collagen within the body contributes to the extensive biological relevance of DNA-collagen complexes. Functional nucleic acids can form these complexes, such as siRNA, antisense oligonucleotides, DNA origami nanostructures, and, in particular, single-stranded DNA aptamers, often distinguished by their rapid self-assembly at room temperature and formation without external stimuli and modifications. The simple and seamless integration of nucleic acids within collagenous matrices enhances biomimicry and targeted bioactivity, and provides stability against enzymatic degradation, positioning DNA-collagen complexes as an advanced biomaterial system for many applications including angiogenesis, bone tissue regeneration, wound healing, and more.

Optimizing Biomimetic 3D Disordered Fibrous Network Structures for Lightweight, High-Strength Materials via Deep Reinforcement Learning.

3D disordered fibrous network structures (3D-DFNS), such as cytoskeletons, collagen matrices, and spider webs, exhibit remarkable material efficiency, lightweight properties, and mechanical adaptability. Despite their widespread in nature, the integration into engineered materials is limited by the lack of study on their complex architectures. This study addresses the challenge by investigating the structure-property relationships and stability of biomimetic 3D-DFNS using large datasets generated through procedural modeling, coarse-grained molecular dynamics simulations, and machine learning. Based on these datasets, a network deep reinforcement learning (N-DRL) framework is developed to optimize its stability, effectively balancing weight reduction with the maintenance of structural integrity. The results reveal a pronounced correlation between the total fiber length in 3D-DFNS and its mechanical properties, where longer fibers enhance stress distribution and stability. Additionally, fiber orientation is also considered as a potential factor influencing stress growth values. Furthermore, the N-DRL model demonstrates superior performance compared to traditional approaches in optimizing network stability while minimizing mass and computational cost. Structural integrity is significantly improved through the addition of triple junctions and the reduction of higher-order nodes. In summary, this study leverages machine learning to optimize biomimetic 3D-DFNS, providing novel insights into the design of lightweight, high-strength materials.

Synergetic role of TRPV4 inhibitor and mechanical loading on reducing inflammation.

Resolution of inflammation is essential for normal tissue healing and regeneration, with macrophages playing a key role in regulating this process through phenotypic changes from a pro-inflammatory to an anti-inflammatory state. Pharmacological and mechanical (mechanotherapy) techniques can be employed to polarize macrophages toward an anti-inflammatory phenotype, thereby diminishing inflammation. One clinically relevant pharmacological approach is the inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4). This study investigates the effects of various mechanical loading amplitudes (0%, 3%, and 6%) and TRPV4 inhibition (10 µM RN-1734) on the phenotypic commitments of pro-inflammatory (M1) macrophages within three-dimensional (3D) collagen matrices. M1 macrophages exposed to 3% mechanical strain exhibited upregulated pro-inflammatory responses, including increased pro-inflammatory gene expression and enhanced proteolytic activity within the extracellular matrix. TRPV4 inhibition partially mitigated this inflammation. Notably, 6% mechanical strain combined with TRPV4 inhibition suppressed Mitogen-Activated Protein Kinase (MAPK) expression, leading to reduced pro-inflammatory gene expression and increased anti-inflammatory markers such as CD206. Gene expression analysis further demonstrated significant reductions in pro-inflammatory gene expression and a synergistic promotion of anti-inflammatory phenotypes under TRPV4 inhibition at 6% mechanical strain. Surface protein analysis via immunohistochemistry confirmed these phenotypic shifts, highlighting changes in the expression of CD80 (pro-inflammatory) and CD206 (anti-inflammatory) markers, alongside F-actin and nuclear staining. This research suggests that TRPV4 inhibition, combined with specific mechanical loading (6%), can drive macrophages toward an anti-inflammatory state, thereby may promote inflammation resolution and tissue repair.

Analysis of the Effect of Human Type I Collagen-Derived Peptide on Bone Regenerative Capacity and Comparison with Various Collagen Materials In Vivo.

Background and Objectives: Autologous bone grafting is the first choice for reconstructive surgery in bone defects due to trauma or malignant tumors. However, there is an increasing demand for minimally invasive alternatives involving bone regeneration using artificial materials. Biomimetic materials that replicate the body's microscopic structure, such as Cellnest®, are gaining attention. Cellnest is a xeno-free recombinant peptide based on human type I collagen, containing a rich Arg-Gly-Asp (RGD) motif related to cell adhesion. The aim of this study was to compare the effects of Cellnest with existing collagen materials (Pelnac®, Integra®, Terudermis®) on bone regeneration and elucidate the underlying mechanisms. Materials and Methods: In vivo experiments involved a rat model of calvarial bone defects, in which Cellnest and other collagen materials were implanted into the defect area. Bone formation was assessed after 4 weeks using micro-computed tomography (micro-CT) and histological analysis. In vitro experiments included the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), adhesion, and migration assays, and a real-time polymerase chain reaction using rapidly expanding cells (RECs) to explore the mechanisms of Cellnest's bone regenerative capacity. Results: The micro-CT analysis showed that the regenerated bone area was significantly greater in the Cellnest group (72.3%) than in the Pelnac® (25.5%), Integra® (31.6%), and Terudermis® (38.3%) groups. The histological analysis confirmed similar trends, with Cellnest showing 42.2% bone regeneration, outperforming the other materials. The in vitro assays revealed that Cellnest promoted cell proliferation, adhesion, and migration. Gene expression analysis demonstrated that Cellnest significantly increased the levels of the bone formation markers ALP and COL1. Conclusions: Cellnest, a human type I collagen-like peptide rich in RGD motifs, enhances bone regeneration by promoting MSC adhesion and migration, and bone formation-related gene expression. The findings suggest its potential as an effective material for bone defect reconstruction.

FRESH extrusion 3D printing of type-1 collagen hydrogels photocrosslinked using ruthenium.

The extrusion bioprinting of collagen material has many applications relevant to tissue engineering and regenerative medicine. Freeform Reversible Embedding of Suspended Hydrogels (FRESH) technology is capable of 3D printing collagen material with the specifications and details needed for precise tissue guidance, a crucial requirement for effective tissue repair. While FRESH has shown repeated success and reliability for extrusion printing, the mechanical properties of completed collagen prints can be improved further by post-print crosslinking methodologies. Photoinitiator-based crosslinking methods are simple and have proven effective in strengthening protein-based materials. The ruthenium and sodium persulfate photoinitiator system (Ru(bpy)3/SPS) has been suggested as an effective crosslinking method for collagen materials. Herein, we describe the procedure our group has developed to combine extrusion-based 3D printing of type-1 collagen using FRESH technology with Ru(bpy)3/SPS photoinitiated crosslinking methods to improve the strength and stability of 3D printed collagen structures. Mechanical testing and cell biocompatibility assessments were performed to investigate the impact of Ru(bpy)3/SPS photoinitiated crosslinking and highlight the potential limitations of this method. These results demonstrate a significant improvement in the compressive strength of type-1 collagen samples as the Ru(bpy)3/SPS concentration increases. Additionally, type-1 collagen samples crosslinked with up to 1/10 mM Ru(bpy)3/SPS support PC12 cell viability over a period of 7 days. The primary limitations that were observed and described in detail in this protocol are: the FRESH slurry preparation, printing environment, extrusion printer hardware, and quality of the ruthenium reagent.

The effectiveness of vitamin C in dental alveolus healing after dental extraction: A scoping review.

Dental extraction is a common procedure in dentistry. It is accompanied by postoperative pain and inflammation. In addition, it decreases bone volume and density. Vitamin C is an antioxidant and cofactor that promotes the synthesis and maturation of collagen, the proliferation and migration of fibroblasts and osteoblasts, accelerating the final phase of inflammation, promoting healing. The objective of this scoping review is to evaluate the effectiveness of vitamin c in dental alveolus healing after extraction and synthesize the available evidence and tits clinical implications. This review is registered on the Open Science Framework platform (https://osf.io/bstwk/). It was carried out under the PRISMA-ScR protocol, using the question: Is vitamin C effective in alveolar healing in patients undergoing dental extraction? The Pubmed/MEDLINE, Scopus, Web of Science and OPENGREY databases were used. Limiting itself to primary studies. A total of 287 articles were identified, applying selection criteria, 3 were included. Of a total of 135 patients, 59.8% were administered vitamin C; 46.6% 600 mg, 34.2% 500 mg and 19.2% 1500 mg. A decrease in pain, inflammation, probing depth and mesiodistal length of the socket was observed. The role of vitamin C is essential for healing, and therefore, bone regeneration after tooth extraction, reducing adverse effects such as pain and inflammation. Its administration is recommended to promote postoperative recovery. More studies are suggested to observe its effects in oral and maxillofacial surgery.

The "HAT-TRICK" technique: A modification of soft tissue grafting using volume stable collagen matrix and cross-linked hyaluronic acid. Part B: Clinical applications in the esthetic zone.

Soft tissue deficiency around dental implants can negatively impact outcomes in terms of esthetics and long-term stability. While autogenous connective tissue grafting is still considered the gold standard treatment, alternative approaches are being proposed primarily to enhance patient comfort and avoid invasive procedures such as two-sites surgeries using xenogeneic collagen matrices. Despite the advantages, the quality of the regenerated tissues remains unpredictable and, in many cases, questionable, highlighting the need for alternative and innovative approaches. After introducing in a previous technical note, the "HAT-TRICK" technique, to address these challenges in pontic sites, the present study highlights the "HAT-TRICK" technique for thickening the keratinized gingiva in both immediate and delayed implant placement sites within the esthetic zone. The "HAT-TRICK" technique is demonstrated through two clinical cases, accompanied by a digital comparison conducted at baseline and after one year of follow-up in order to assess and quantify the augmented areas.

DESMOPLASTIC FIBROMA OF THE MANDIBLE: A RARECASE REPORT AND REVIEW OF THE LITERATURE

Objectives: The desmoplastic fibroma (DF) is a rare, benign, diffuse, infiltrative proliferation of fibroblasts and mature collagen that typically occurs in the first three decades of life. Jaffe first outlined it in 1958.The mandible represents the fourth most affected site, and mandibular (84%) posterior location is favored. The clinical, radiological and histological presentation of desmoplastic fibroma can resemble various other jawbone lesions. The most common treatment for desmoplastic fibroma is block resection or wide local excision, a follow up period of 3 years is recommended. Case Report: A 12-year-old male applied to our clinic with an expanding swelling at the anterior of his mandible. The patient had a stable medical history. Extraoral examination revealed a slight expansion of the right anterior border of the mandible. Intraoral swelling resembled a hard bony texture and there was no inflammation noted. A panoramic radiograph indicated periost reaction at the lower border of the mandible and radiolucent lesion. Incisional biopsy taken. Microscopic examination pointed DF. Treatment option was marginal resection due to aggressive behavior of DP. Resection included 3 mm of healthy bone tissue around the lesion. No recurrencies was observed after 3-and 6-month follow-ups and will be followed for several years. Conclusion: The purpose of this case report is to examine the diagnosis and treatment approaches for desmoid tumors in the maxillofacial region, a condition with very few cases reported so far, in the context of existing literature.

Evaluation of radiation therapy on grafted and non-grafted defects: an experimental rat model.

This study aimed to assess the effects of a single-dose radiation therapy (15 Gy) on grafted and non-grafted defects, bone microarchitecture, and collagen maturity. Bone defects were surgically created in rat femurs. The right femur defect was filled with blood clot (group "Clot") and the left femur defect by deproteinized bovine bone mineral graft (group "Xenograft"). The animals were divided into two groups: without radiation therapy (nRTX) and with radiation therapy (RTX). Microtomographic (bone volume fraction, BV/TV; trabecular thickness, Tb.Th; trabecular number, Tb.N; trabecular separation, Tb.Sp), histological, and histomorphometric analyses were performed 14 days after the surgery. Two-way ANOVA with Tukey post hoc test was used to compare the groups (α=5%). Microtomographic analysis revealed that radiation therapy led to smaller BV/TV and Tb.N in both Clot and Xenograft groups. Regardless of radiation therapy, defects filled with xenografts showed a larger Tb.N. In contrast, the Clot group demonstrated increased BV/TV and Tb.Th. The histomorphometric results were consistent with those obtained by microtomography. Intermediately and densely packed collagen were predominant among the groups. Histological analysis revealed disorganized bone formation bridging the cortical borders of the lesions in the RTX group. The involvement of primary bone with graft particles was commonly observed in all xenograft groups, and radiation therapy did not affect the percentage of bone-graft contact. Single-dose radiation therapy affected bone repair, resulting in a smaller amount of newly formed bone in both grafted and non-grafted defects.

Comparison of cell-scaffold interactions in a biological and a synthetic wound matrix.

Wound healing is a central physiological process that restores the barrier properties of the skin after injury, comprising close coordination between several cell types (including fibroblasts and macrophages) in the wound bed. The complex mechanisms involved are executed and regulated by an equally complex, reciprocal signalling network involving numerous signalling molecules such as catabolic and anabolic inflammatory mediators (e.g., cytokines, chemokines). In chronic wound environments, the balance in the molecular signatures of inflammatory mediators is usually impaired. Thus, we compared the ability of a collagen-based wound matrix against a synthetic wound matrix to attract fibroblasts and macrophages that deliver these signalling molecules. In particular, the balance between pro- and anti- inflammatory cytokine secretion was assessed. We found that the natural collagen-based matrix was the most efficient adhesive substrate to recruit and activate fibroblasts and macrophages on its surface. These cells secreted a variety of cytokines, and the natural biomaterial exhibited a more balanced secretion of pro- and anti-inflammatory mediators than the synthetic comparator. Thus, our study highlights the ability of native collagen matrices to modulate inflammatory mediator signatures in the wound bed, indicating that such devices may be beneficial for wound healing in the clinical setting.

Review: Application of Protein-Based Raw Materials in Health Foods in China

Raw protein materials are beneficial for human health, so they are being increasingly used in health foods. In recent years, there has been more and more research on and applications of raw protein materials, but few teams have conducted a detailed review of the application status of raw protein materials in China’s health foods, the basis for their compliance and use, and the research on their health care functions. Therefore, this review evaluates the application of animal and plant proteins in China’s health foods, the impact of animal and plant proteins on human health, and future research recommendations for animal and plant proteins. This review analyzes and discusses the data on approved health foods that have been verified to contain raw protein materials (mainly including the number of protein health foods approved over the years, the classification of raw protein materials and types of relevant regulations, the analysis of the frequency of use of raw protein materials, and the functions of approved health foods). Through this process, the application of raw protein materials in health foods in China is systematically reviewed. In short, through data analysis, this study found that in 1996~2024, a total of 1142 health foods containing raw protein materials were approved in China, which are mainly divided into animal proteins, vegetable proteins, microbial proteins, and peptide raw materials, and peptide raw materials comprise the majority. The compliance applications of these ingredients are mainly related to China’s five categories of food regulations. The results show the following for health foods containing raw protein materials: in terms of the dosage form, they are mainly solid preparations; according to their functional claims, they mainly help to enhance immunity, help improve bone density, help improve skin moisture, and relieve physical fatigue; and in the application of raw materials, it is found that the use of raw materials such as casein phosphopeptide, soybean protein isolate, whey protein, collagen, spirulina, and other raw materials in products is relatively high. Finally, based on these studies, this paper discusses suggestions for raw protein materials in the future development of health food in China and also discusses the limitations of the current research in this review.

Distribution and Maturity of Medial Collagen Fibers in Thoracoabdominal Post-Dissection Aortic Aneurysms: A Comparative Study of Marfan and Non-Marfan Patients.

Thoracoabdominal aortic aneurysms (TAAAs) are rare but serious conditions characterized by dilation of the aorta characterized by remodeling of the vessel wall, with changes in the elastin and collagen content. Individuals with Marfan syndrome have a genetic predisposition for elastic fiber fragmentation and elastin degradation and are prone to early aneurysm formation and progression. Our objective was to analyze the medial collagen characteristics through histological, polarized light microscopy, and electron microscopy methods across the thoracic and abdominal aorta in twenty-five patients undergoing open surgical repair, including nine with Marfan syndrome. While age at surgery differed significantly between the groups, maximum aortic diameter and aneurysm extent did not. Collagen content increased from thoracic to infrarenal segments in both cohorts, with non-Marfan patients exhibiting higher collagen percentages, notably in the infrarenal aorta (729.3 nm vs. 1068.3 nm, p = 0.02). Both groups predominantly displayed mature collagen fibers, with the suprarenal segment containing the highest proportion of less mature fibers. Electron microscopy revealed comparable collagen fibril diameters across segments irrespective of Marfan status. Our findings underscore non-uniform histological patterns in TAAAs and suggest that ECM remodeling involves mature collagen deposition, albeit with lower collagen content observed in the infrarenal aorta of Marfan patients.

Silybum marianum Extract: A Highly Effective Natural Alternative to Retinoids to Prevent Skin Aging Without Side Effects.

Vitamin A, or retinol, is one of the most effective antiaging molecules, but it presents issues with photo-sensitivity and irritation. Alternatives are emerging, but have so far been less effective. Here, we present a Silibum marianum extract (SME) as a retinol-like ingredient providing both safety and efficacy. SME was compared to the reference compound, retinol, and to the main alternative, bakuchiol. Skin explants from a 58-year-old donor were treated with pure retinol (0.1%), bakuchiol (0.2%), or SME (0.8%). After 5 days, collagen and hyaluronic acid levels were analyzed. A placebo-controlled study involving 57 volunteers was also conducted, with products applied twice daily for 56 days. Results were measured by AEVA-HE and VISA. Levels of collagen III were significantly increased by SME, by 23% and 16% compared to bakuchiol and retinol respectively. Compared to bakuchiol, SME treatment increased hyaluronic acid production by 36%. In clinical tests, SME had a significantly stronger anti-wrinkle effect than bakuchiol-reducing the number of wrinkles on the forehead by 21% and their circumference by 17%-producing effects similar to retinol, and better than bakuchiol. In the self-assessment, 43% of volunteers reported discomfort while using retinol compared to 0% for the SME formulation. By enhancing levels of collagen III-the youth collagen-and hyaluronic acid in the skin, SME paves the way for the maturation of collagen I fibrils and skin plumping. With its stronger efficacy compared to bakuchiol and enhanced safety profile compared to retinol, SME may be the next generation of natural alternatives to retinoids.

Evaluation of wound healing efficiency using collagen matrices on a thermal burn model

Every year dozens of new local wound treatment agents are developed and improved in the world, which undergo preliminary testing on laboratory animals due to the presence of common phases of the wound healing process with humans. Wound healing effect was studied on a thermal burn model on Wistar rats in 4 groups: 1st - control (natural wound healing); 2nd - intact animals (normal, without burn). 3rd - experimental ( collagen treatment ); 4th - experimental 2 , comparison group (" Levomekol "); Wound healing was assessed based on the results of planimetry on the 1st, 3rd, 5th, 7th, 9th and 13th days and histological analysis of skin tissue on the 6th, 13th and 20th days. Results. Thermal skin damage resulted in a IIIA degree burn, accompanied by the development of dry coagulation necrosis. The use of collagen matrices restored the total leukocyte count and reduced the area of the burn wound. Histomorphometric studies confirmed the dynamics of skin tissue recovery after the burn. The effectiveness of the matrices was comparable to the pharmacopoeial drug " Levomekol ". A higher wound-healing effect was noted with the use of collagen. Conclusion. The wound-healing effect of collagen matrices was established on the thermal burn model, as evidenced by the results of restoration of the number of leukocytes, reduction of the burn wound area and restoration of the skin histostructure .

A review: the therapeutic power of natural extracts in wound recovery

Natural extracts from plants, herbs, and other biological sources have demonstrated substantial potential in wound healing through their diverse biochemical activities, primarily attributed to active compounds such as alkaloids, flavonoids, phenols, and terpenoids. These compounds facilitate wound healing across various stages, including hemostasis, inflammation, proliferation, and remodeling, by modulating cellular responses, promoting tissue regeneration, and minimizing scar formation. During the hemostasis phase, natural extracts enhance platelet aggregation and fibrin formation, creating an initial matrix conducive to cell migration. In the inflammation phase, these extracts exhibit antioxidant and anti-inflammatory effects, reducing the production of pro-inflammatory cytokines and reactive oxygen species (ROS) and contributing to chronic inflammation. This anti-inflammatory activity accelerates the transition to the proliferative phase, where active compounds stimulate fibroblast and keratinocyte proliferation, promoting collagen synthesis and angiogenesis critical for new tissue formation. During the remodeling phase, natural extracts aid in collagen reorganization and maturation, improving tissue strength and elasticity while minimizing excessive scarring. However, despite the benefits, challenges such as limited bioavailability, stability, and inconsistent dosing hinder clinical applications. Advanced delivery systems, including nanofibers and hydrogels, are being explored to improve the stability and efficacy of these bioactive compounds. This review synthesizes recent research on the biochemical mechanisms of natural extracts in wound healing, outlines the clinical challenges, and highlights future directions for enhancing their therapeutic utility.

Age-related remodeling of the vocal fold extracellular matrix composition, structure, and biomechanics during tissue maturation

ABSTRACT Purpose The vocal folds (VFs) are among the most mechanically active connective tissues, vibrating between 80 and 250 hz during speech. Overall VF function is determined by the composition and structure of their extracellular matrix (ECM). During tissue maturation, the VFs remodel from a monolayer of collagen fibers to a tri-layered structure, affecting tissue biomechanics. However, age-related VF ECM remodeling remains poorly understood since few studies have explored the proteins governing collagen fibrillogenesis or the non-collagenous ECM components critical for VF elasticity. Materials and Methods VFs from immature, sexually mature, and skeletally mature rats were evaluated by endoscopy, histology, and electron microscopy for cellular and biochemical composition, ECM organization, and proteoglycan distribution. Nanoindentation modulus was determined by atomic force microscopy. Results Collagen fiber abundance, maturity, and alignment are low in immature rats but show an age-dependent increase during tissue maturation. Lumican and fibromodulin, which regulate early-stage collagen fibril formation, are distributed throughout the VFs, and their abundance decreases with age. Decorin, involved in collagen organization, is concentrated just beneath the epithelium and increases with age. Elastin levels increase during tissue maturation, but hyaluronic acid abundance and distribution remain consistent with age. VF nanoindentation modulus trends toward a decrease with age. Conclusion This work identifies changes in VF ECM composition and organization during tissue maturation, focusing on proteins that regulate collagen fibrillogenesis, fiber assembly, and VF biomechanics. These findings may inform the development of pro-reparative therapies designed to influence collagen network structure and overall ECM dysregulation in a number of laryngeal pathologies.

CCL2/CCR2 Signalling in Mesenchymal Stem/Progenitor Cell Recruitment and Fracture Healing in Mice

ABSTRACTMacrophage efferocytosis (clearance of apoptotic cells) is crucial for tissue homeostasis and wound repair, where macrophages secrete factors that promote resolution of inflammation and regenerative signalling. This study examined the role of efferocytic macrophage‐associated CCL2 secretion, its influence on mesenchymal stem/progenitor cell (MSPC) chemotaxis, and in vivo cell recruitment using Ccr2−/− (KO) mice with disrupted CCL2 receptor signalling in two regenerative models: ossicle implants and ulnar stress fractures. Single cell RNA sequencing and PCR validation indicated that efferocytosis of various apoptotic cells at bone injury sites (osteoblasts, pre‐osteoblasts, MSPC) upregulated CCL2. CCL2 gradients enhanced MSPC migration through type I collagen matrices. In vivo, MSPC (LepR+) infiltration was significantly reduced while macrophage (F4/80+) infiltration increased in KO ossicle implants versus WT. In ulnar stress fractures, micro‐CT revealed increased mineralized callus incidence in CCR2 KO male mice 5 days post injury (dpi) versus WT. By 7‐dpi callus fractional bone volume, trabecular thickness, and bone mineral density were increased versus WT. Immunohistochemistry of mice 5‐dpi confirmed an increase in callus area (including soft tissue); however, the percent of osteoprogenitors (%Osx+) within the callus was not different. These findings suggest that CCL2 differentially impacts MSPC recruitment depending on bone wound healing model.

Zinc Oxide-Based Endodontic Sealer with Proanthocyanidin-PLGA Nanoparticles: Synthesis and Physical Characterization

This study developed a zinc oxide-based endodontic sealer incorporating proanthocyanidin nanoparticles (PAC-NPs) encapsulated in poly(lactic-co-glycolic acid) (PLGA), utilizing PAC’s proven ability to enhance dentine collagen stability. The formulation was designed to provide both antimicrobial and collagen-stabilizing benefits, aiming to improve dentine-sealer interface integrity and prolong the functional lifespan of root canal treatments. Chemical characterization was conducted using Fourier Transform Infrared (ATR-FTIR) spectroscopy, confirming the presence of Zn-O and C=O bonds, indicative of the successful integration of zinc oxide and encapsulated PAC. Physical properties, including flow, setting time, solubility, and dimensional stability, were evaluated according to ISO 6876:2012 and ANSI/ADA standards 57, with the sealer meeting all clinical performance criteria. This preliminary characterization of the physical and chemical properties establishes a basis for further in vitro studies on the mechanical and biological performance of the sealer, aimed at validating its potential to enhance dentine collagen stabilization and material durability in endodontic applications.