Collagen Matrices Research Articles

Exploring the Role of Spatial Confinement in Immune Cell Recruitment and Regeneration of Skin Wounds.

Microporous annealed particle (MAP) scaffolds are injectable granular materials comprised of micron sized hydrogel particles (microgels). The diameter of these microgels directly determines the size of the interconnected void space between particles where infiltrating or encapsulated cells reside. This tunable porosity allows the authors to use MAP scaffolds to study the impact of spatial confinement (SC) on both cellular behaviors and the host response to biomaterials. Despite previous studies showing that pore size and SC influence cellular phenotypes, including mitigating macrophage inflammatory response, there is still a gap in knowledge regarding how SC within a biomaterial modulates immune cell recruitment in vivo in wounds and implants. Thus, the immune cell profile within confined and unconfined biomaterials is studied using small (40µm), medium (70µm), and large (130µm) diameter spherical microgels, respectively. This work uncovered that MAP scaffolds impart regenerative wound healing with an IgG1-biased Th2 response. MAP scaffolds made with large microgels promote a balanced pro-regenerative macrophage response, resulting in enhanced wound healing with mature collagen regeneration and reduced inflammation levels.

Covering skin defects with a xenogeneic collagen matrix in comparison with a skin graft – A multicenter randomized controlled trial

The objective of this study was to analyze, in a randomized controlled multicenter trial, whether a xenogeneic collagen matrix (XCM) could be used to cover skin defects. Patients with the need for skin excisions were recruited and randomized to treatment with a skin graft after a period of granulation or to treatment with an XCM. The results were evaluated by two independent observers on the Patient and Observer Scar Assessment Scale. On this scale, scars are ranked from 1 to 10 in six different categories. Results range from 6 to 60, with lower scores representing scars closer to normal skin. The results 6 months after reconstruction were used as primary endpoint and compared in a non-inferiority approach. A total of 39 wounds in the head and neck region were analyzed. The mean results were 16.55 (standard deviation 6.8) for XCM and 16.83 (standard deviation 8.21) in the control group. The result of the XCM was not significantly inferior to the result of the skin graft (p = 0.91). Within the limitations of the study, it seems that the use of xenogeneic collagen matrices is a viable alternative to other approaches in small skin defects, and therefore should be taken into account whenever the reduction of patient morbidity to a minimum is the priority. Trial registrationThis trial was registered in the German Clinical Trials Register under registration identification number DRKS00010930 and can be found under the following URLs: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00010930.https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00010930.

Preliminary study of some of the main intratumor stroma components in gastric carcinomas.

The relationship between stromal compartment and tumor behavior in gastric carcinomas is still poorly understood and defined. Therefore, the authors started, with this preliminary study, an analysis of stromal compartment morphology and behavior in tumors arising from gastric mucosa epithelium. The study group included 75 patients operated for gastric carcinoma. Five parameters describing tumor morphology and behavior and eight parameters describing tumor stroma (TS) morphology were assessed. Histopathological examination included six serial sections of formalin-fixed, paraffin-embedded tumor tissue samples, stained with three classical stains and three antibodies to reveal the different parameters. For data comparison, Pearson's correlation test and the chi-squared (χ²) correlation test were used. Studied tumors were, usually, infiltrating, undifferentiated∕diffuse type, invasive in subserous spaces and with a Ki67 index higher than 20%. Collagen fibers dominated the stromal components, with a predominance of mature type and an average fibrillary index of 2.7. The whole amount of stromal components accounted for around one quarter of the tumor area. Mature collagen fibers were in opposite correlation with their immature counterpart, and both were in opposite correlation with smooth muscle fibers and expressed an opposite trend of correlation with components of vascular compartment. The whole amount of stromal components had divergent behavior with the components of vascular compartment. The latter expressed generally an opposite trend of correlation with individual fibrillary stromal components. We found only isolated relationships statistically significant between stromal components and tumor characteristics. TS is in a continuous remodeling process in relation to the evolution of tumor parenchyma, tumors less differentiated proving to have an immature stroma, with newly formed collagen fibers and higher vascular density. Further studies are required.

Comparative analysis of xenogeneic collagen matrix and autogenous subepithelial connective tissue graft to increase soft tissue volume around dental implants: a systematic review and meta-analysis

ObjectiveThe gold standard for a soft tissue augmentation around implants is a subepithelial connective tissue graft (CTG), but the xenogeneic collagen matrices (XCM) started to be used as an alternative. This systematic review aimed to assess the effectiveness XCM in comparison to CTG for the increasing the thickness of the soft tissue around implants.DataAll studies included at least two parallel groups comparing the use of CTG and XCM with a minimum follow-up of 3 months. As the primary outcome, the amount of soft tissue thickness gain after soft tissue augmentation with XCM or CTG was assessed. Secondary outcomes were clinical and patient-related outcomes; evaluation of aesthetic outcomes, patient-reported outcomes measures (PROMs) and complications. Eligible studies were selected based on the inclusion criteria. Meta-analysis was applied whenever possible. The quality of the evidence of studies including in meta-analysis was assessed using the GRADE approach.SourceA systematic literature search up to January 2022 was conducted using the following electronic databases: PubMed (MEDLINE), Scopus, Cochrane Library, LILACS, eLIBRARY.RU. Unpublished researches, the gray literature, nonprofit reports, government studies and other materials were reviewed electronically using an EASY search. An additional manual search was carried out in November 2022.Study selectionOf the 1376 articles from the initial search, 8 randomized controlled trials (RCTs) (306 patients and 325 implants) were included in this systematic review, and 7 studies were part of the meta-analysis. Meta-analysis revealed that XCM is less effective than the CTG in increasing soft tissue thickness around dental implants. However, XCM also provides soft tissue thickness gain and can be recommended for use in various clinical situations.Clinical significancePrevious systematic reviews and meta-analyses have shown that autologous grafts are more effective than collagen matrices in increasing soft tissue thickness, however, the latter can be used as an alternative. Studies included in previous systematic reviews varied in design, which could lead to limitations. The present systematic review and meta-analysis includes for the first time only randomized controlled clinical trials with collagen matrix of xenogeneic origin in the test group. Tight eligibility criteria were established, and the main parameter studied was soft tissue thickness. It was found that xenogeneic collagen matrix is effective for increasing soft tissue thickness around dental implants, however, the results obtained using an autogenous connective tissue graft are superior.

Biocompatibility, Biomineralization and Induction of Collagen Maturation with the Use of Calcium Hydroxide and Iodoform Intracanal Dressing.

Biocompatibility and biomineralization of root canal dressings are important requirements for periapical healing. This study evaluated the inflammatory response, biomineralization and tissue repair by collagen fiber maturation in the subcutaneous tissue of rats. Eighteen Wistar rats (n = 6) received subcutaneous implants: calcium hydroxide + propylene glycol [CH+P], calcium hydroxide + propylene glycol + iodoform [CH+P+I], iodoform + carbowax [I+Cwax] and carbowax [Cwax]. Extra empty tubes were used as a control [C]. After 7, 15 and 30 days, the implants were removed with surrounding tissue for staining of hematoxylin-eosin, Von Kossa, picrosirius red and without staining for analysis under polarized light. Results were analyzed via Kruskal-Wallis followed by Dunn testing for nonparametric data and ANOVA followed by a Tukey post hoc test for parametric data (p < 5%). At 7 days, all groups showed a moderate inflammatory reaction and thick fibrous capsule, except the [Cwax] group, with a severe inflammatory infiltrate (p < 0.05). After 15 days, all groups but control had a decrease in inflammatory response. At 30 days, all groups presented a mild reaction and thin fibrous capsule (p > 0.05). Only groups containing calcium hydroxide were found to be positive using Von Kossa staining and polarized light in all periods. At 7 days, all groups showed a higher proportion of immature fibers. At 15 days, the [CH+P] and [Cwax] groups increased their proportion of mature/immature fibers. At 30 days, only the [CH+P] group presented a significant prevalence of mature collagen fibers (p < 0.05). All groups showed biocompatibility, but only groups containing calcium hydroxide induced biomineralization. The addition of iodoform delayed tissue healing.

Killing two birds with one stone: A therapeutic copper-loaded bio-patch promoted abdominal wall repair via VEGF pathway.

Hernia and life-threatening intestinal obstruction often result from abdominal wall injuries, and the regeneration of abdominal wall defects is limited due to the lack of biocompatible, antibacterial and angiogenic scaffolding materials for treating injured tissues. Taking inspiration from the facile preparation of dopamine polymerization and its surface modification technology, in this study, multi-therapeutic copper element was introduced into porcine small intestinal submucosa (SIS) bio-patches through polydopamine (PDA) deposition, in order to regenerate abdominal wall injury. In both in vitro antibacterial assays, cytocompatibility assays and in vivo abdominal wall repair experiments, the SIS/PDA/Cu bio-patches exhibited robust antibacterial efficiency (＞99%), excellent biocompatibility to cells (＞90%), and enhanced neovascularization and improved collagen maturity compared to other commercially available patches (3.0-fold higher than the PP mesh), due to their activation of VEGF pathway. These findings indicated the bio-patch was a promising application for preventing visceral adhesion, bacterial infection, and promoting soft tissue regeneration.

Mutable Collagenous Tissue Isolated from Echinoderms Leads to the Production of a Dermal Template That Is Biocompatible and Effective for Wound Healing in Rats.

The mutable collagenous tissue (MCT) of echinoderms possesses biological peculiarities that facilitate native collagen extraction and employment for biomedical applications such as regenerative purposes for the treatment of skin wounds. Strategies for skin regeneration have been developed and dermal substitutes have been used to cover the lesion to facilitate cell proliferation, although very little is known about the application of novel matrix obtained from marine collagen. From food waste we isolated eco-friendly collagen, naturally enriched with glycosaminoglycans, to produce an innovative marine-derived biomaterial assembled as a novel bi-layered skin substitute (Marine Collagen Dermal Template or MCDT). The present work carried out a preliminary experimental in vivo comparative analysis between the MCDT and Integra, one of the most widely used dermal templates for wound management, in a rat model of full-thickness skin wounds. Clinical, histological, and molecular evaluations showed that the MCDT might be a valuable tool in promoting and supporting skin wound healing: it is biocompatible, as no adverse reactions were observed, along with stimulating angiogenesis and the deposition of mature collagen. Therefore, the two dermal templates used in this study displayed similar biocompatibility and outcome with focus on full-thickness skin wounds, although a peculiar cellular behavior involving the angiogenesis process was observed for the MCDT.

Natural vs Synthetic Polymers: How Do They Communicate with Cells for Skin Regeneration—A Review

Modern research has evolved several approaches toward skin regeneration and one of the novel concerns is the use of polymer-based systems due to their excellent beneficial properties to the skin. Several polymers, such as cellulose, hyaluronan, alginate, chitosan, collagen, fibrin and fibroin, have been tested and have proven the benefits for skin regeneration, and most of them are derived from either polysaccharide- or protein-based materials. In order to understand the mode of action, several researchers investigated the cell–matrix interaction and possible signaling mechanism in skin regeneration. Not only the signaling mechanism but also the mode of cell communication determines the application of polysaccharide- and protein-based polymers in practice. Based on the above significance, this review disclosed the recent findings to compile a possible method of communication between cells and polymers derived from polysaccharide-based (such as cellulose, hyaluronan, chitosan, alginate, agar, and xanthan gum) and protein-based (such as collagen, gelatin, fibrin, and silk fibroin) materials along with other polymers, such as poly(vinyl alcohol), polyglycolide or poly(glycolic acid), or poly(lactic acid) in skin regeneration. Accordingly, this review addresses the fundamental concept of cell–matrix communication, which helps us to understand the basis of the polymer’s functions in the biomedical field.

Influence of Phosphoric, Glycolic, and Ferulic Acids on Dentin Enzymatic Degradation, Ultimate Tensile Strength, and Permeability.

This study evaluated dentin enzymatic degradation based on the total matrix metalloproteinase (MMP) activity of demineralized dentin matrices before and after exposure to phosphoric acid (PA), glycolic acid (GA), and ferulic acid (FA). The release of hydroxyproline (HP), ultimate tensile strength (UTS), and dentin permeability (DP) were also evaluated. Dentin collagen matrices were assessed according to total MMP activity before and after treatment with the tested acids (n=10) for 15 seconds and compared with the control (GM6001 inhibitor). Dentin beams were analyzed for HP release and UTS after the treatments. Dentin discs were tested for DP at a pressure of 5 psi before and after treatment with the acids (n=10). The FA group had a lower percentage of enzymatic inhibition than the PA and GA groups (p<0.0001). No significant difference in UTS was found among the acids (p=0.6824), but HP release was significantly higher in the FA group than in the PA and GA groups (p<0.0001). No significant difference in DP was found for the acids (p=0.0535). GA led to less activation of MMPs and less release of HP, whereas the UTS and DP for GA were like those found for PA. In contrast, FA promoted greater enzymatic activity and greater release of HP, while having similar results to GA and PA regarding mechanical properties.

Engineered Biomaterials Trigger Remineralization and Antimicrobial Effects for Dental Caries Restoration.

Dental caries is the most prevalent chronic disease globally, significantly impacting individuals' quality of life. A key reason behind the failure of implanted restorations is their biological inactivity, meaning they are unable to form crosslinks with the surrounding tooth structures, thus making patients susceptible to implant loss and recurrent tooth decay. For the treatment of caries, antibacterial medicine and remineralization are effective means of treating the recurrence of caries. Owing to the rapid progression in the biomaterials field, several biomaterials have been reported to display antimicrobial properties and aid in dentin remineralization. Bioactive materials hold considerable potential in diminishing biofilm accumulation, inhibiting the process of demineralization, enabling dentin remineralization, and combating bacteria related to caries. Bioactive materials, such as fluoride, amorphous calcium phosphate, bioactive glass, collagen, and resin-based materials, have demonstrated their effectiveness in promoting dentin remineralization and exerting antibacterial effects on dental caries. However, the concentration of fluoride needs to be strictly controlled. Although amorphous calcium phosphate can provide the necessary calcium and phosphorus ions for remineralization, it falls short in delivering the mechanical strength required for oral mastication. Resin-based materials also offer different advantages due to the complexity of their design. In this review, we delve into the application of advanced bioactive materials for enhancing dentin remineralization and antibacterial properties. We eagerly anticipate future developments in bioactive materials for the treatment of dental caries.

Corneal Wound Healing in the Presence of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot Study.

Highly organized collagen fibrils interlacing with proteoglycans form the crucial architecture of the cornea and facilitate its transparency. Corneal scarring from accidental injury, surgery, or infection alters this highly organized tissue, causing severe consequences, including blindness. There are no pharmacological or surgical methods to effectively and safely treat excessive corneal scarring. Thus, we tested the anticorneal scarring utility of a rationally designed anticollagen antibody (ACA) whose antifibrotic effects have already been demonstrated in nonocular models. Utilizing a rabbit model with an incisional corneal wound, we analyzed ACA's effects on forming collagen and proteoglycan-rich extracellular matrices in scar neotissue. We used microscopic and spectroscopic techniques to quantify these components and measure crucial parameters characterizing the structure and organization of collagen fibrils. Moreover, we analyzed the spatial distribution of collagen and proteoglycans in normal and healing corneas. Our study demonstrated significant changes in the quality and quantity of the analyzed molecules synthesized in scar neotissue. It showed that these changes extend beyond incision margins. It also showed ACA's positive impact on some crucial parameters defining proper cornea structure. This pilot study provides a stepping stone for future tests of therapeutic approaches that target corneal extracellular scar matrix assembly.

Impact of 3D collagen-based model and hydrostatic pressure on periodontal ligament fibroblast: A morpho-biochemical analysis

This study developed a customized hydrostatic pressure-based loading environment to investigate the effect of static hydrostatic pressure on the periodontal ligament fibroblasts (PDLf) in a three-dimensional (3D) collagen-based model. The cylindrical tissue constructs were comprised of PDL fibroblast cells seeded in type I collagen matrices and divided into three experimental groups: Control (no load), low-load (∼0.07 kPa), and high-load (∼60 kPa), all subjected to 24 h of experimental duration. Cells in the 3D construct were stained with fluorophore-conjugated antibodies for cytoskeletal protein F-actin and matricellular protein periostin. Cell culture supernatant was assessed for receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) expression. Transmission electron microscopy examined the contact between the cells and the collagen matrix. Ultrastructural changes in the 3D collagen matrix were also analyzed using scanning electron microscopy. Experiments were performed in triplicates, and data was analyzed using one-way ANOVA (p < 0.05). The 3D PDLf constructs from the low-load group demonstrated the highest levels of homogeneous cell distribution and higher expression of F-actin and periostin with enhanced interaction with the matrix. The collagen matrix in this group showed more closely packed fibers forming thicker bundles when compared to the control and the high-load 3D PDLf constructs. Nonuniform cell distribution with decreased expression of F-actin and periostin was observed in the control and high-load PDLf constructs. The high-load group showed the highest RANKL/OPG expression. This study demonstrated low-level hydrostatic pressure's role in regulating PDLf functions and extracellular matrix response, while excessive hydrostatic pressure may be detrimental to PDL fibroblast cell function.

Using x-ray micro computed tomography to quantify intracochlear fibrosis after cochlear implantation in a Guinea pig model

Cochlear implants (CIs) allow individuals with profound hearing loss to understand speech and perceive sounds. However, not all patients obtain the full benefits that CIs can provide and the cause of this disparity is not fully understood. One possible factor for the variability in outcomes after cochlear implantation, is the development of fibrotic scar tissue around the implanted electrode. It has been hypothesised that limiting the extent of fibrosis after implantation may improve overall CI function, and longevity of the device. Currently, histology is often used to quantify the extent of intracochlear tissue growth after implantation however this method is labour intensive, time-consuming, often involves significant user bias, and causes physical distortion of the fibrosis. Therefore, this study aimed to evaluate x-ray micro computed tomography (μCT) as a method to measure the amount and distribution of fibrosis in a guinea pig model of cochlear implantation. Adult guinea pigs were implanted with an inactive electrode, and cochleae harvested eight weeks later (n = 7) and analysed using μCT, to quantify the extent of tissue reaction, followed by histological analysis to confirm that the tissue was indeed fibrotic. Cochleae harvested from an additional six animals following implantation were analysed by μCT, before and after contrast staining with osmium tetroxide (OsO4), to enhance the visualisation of soft tissues within the cochlea, including the tissue reaction. Independent analysis by two observers showed that the quantification method was robust and provided additional information on the distribution of the response within the cochlea. Histological analysis revealed that μCT visualised dense collagenous material and new bone formation but did not capture loose, areolar fibrotic tissue. Treatment with OsO4 significantly enhanced the visible tissue reaction detected using μCT. Overall, μCT is an alternative and reliable method that can be used to quantify the extent of the CI-induced intracochlear tissue response and will be a useful tool for the in vivo assessment of novel anti-fibrotic treatments.

Role of Collagen in the Etiology of Inguinal Hernia Patients: A Case-Control Study.

Introduction Technical faults are no longer accepted as the sole reason for recurrence following inguinal hernia (InH) repairs. Medical literature has been studied to find any contributing factors and collagen has emerged as a promising marker. Owing to their long half-lives, it has been found to best reflect the process of scarring, which is central to ensuring the formation of a proper fibrous tissue that incorporates the mesh with the abdominal wall. Methods Sixty participants were divided into two groups. The case group were patients diagnosed with InH and the control group had patients undergoing abdominal surgeries for indications other than abdominal wall hernias. A 0.5x0.5cm specimen of skin and transversalis fascia were biopsied and subsequently stained to determine the amount of collagen I and III. Results Collagen I, collagen III and the ratio of collagen I to III was measured. Collagen I was normal in the skin of both groups but decreased in transversalis fascia of cases. Collagen III was found to be normal in transversalis fascia of both cases and controls, but increased in the skin of cases. Ratio of collagen I to III was decreased in both skin and transversalis fascia of cases. Statistical analysis was carried out using an unpaired t-test, non-parametric Mann-Whitney test, ANOVA and chi-square test. Conclusions Our study has reported that in patients with inguinal hernia, collagen III or immature collagen is increased in skin and collagen I or mature collagen is decreased in the transversalis fascia. The ratio of collagen I/III is decreased in both skin and transversalis fascia.

Chitosan thread in the healing of the cecal wall of rabbits (Oryctolagus cuniculus) submitted to cecorrhaphy.

The development and evaluation of synthesis materials are crucial to reducing the morbidity and magnitude of post-enterorrhaphy surgical complications. Despite the possibility of production, chitosan thread has not yet been used in enterorrhaphy, and its effects on intestinal healing have not been evaluated. Therefore, this study aimed to evaluate the effects of chitosan thread on the intestinal wall repair of rabbits submitted to cecorrhaphy. For this, 42 rabbits were allocated into two groups with 21 animals. One group was submitted to cecorrhaphy with chitosan suture thread (CG) and the other with poliglecaprone suture thread (PG). The occurrence of postoperative complications, the intensity of edema, cellular response, formation of granulation tissue, as well as the deposition and maturation of collagen fibers, and the intensity of vascular endothelial growth factor (VEGF-α) expression, were evaluated during the intestinal wall repair process. The evaluations occurred on the 5th, 15th, and 25th postoperative (PO) days. The animals did not develop peritonitis, but adherence was observed in six animals from CG and seven from PG, with no difference between groups. The polymorphonuclear infiltrate showed higher intensity and higher amount of type III collagen fibers in CG on the 15th PO day. In contrast, a lower amount of type I collagen fibers was observed in CG samples on the 25th PO day. Therefore, the chitosan thread used for cecorrhaphy in rabbits results in minimal postoperative complications, presents biocompatibility, and bioactively assists the tissue repair process of the cecal wall, inducing minimal tissue reaction, stimulating the deposition of type III collagen fibers in the proliferative phase, with sustained VEGF-α expression, but with reduced deposition of type I fibers, indicating a delay in collagen maturation.

Biocompatibility Study with Baby Hamster Kidney Cells on Acetobacter Xylinum Pellicle for Diabetic Foot Laceration

Diabetes mellitus, commonly known as diabetes, is a persistent metabolic condition marked by elevated blood glucose levels. This condition's global prevalence has been consistently increasing, becoming a major cause for concern in public health on an international scale. This disease can lead to various complications, including impaired wound healing. The purpose of this study is to determine the cytotoxicity level of hydrogel membranes made from Acetobacter xylinum and whether the used method is appropriate for producing proper wound healing material. The findings of the study, employing BHK Kidney cells and the MTT Assay technique, revealed that the dehydrated hydrogel membrane derived from bacterial cellulose and processed through oven drying exhibited a toxicity level of less than 50% across all samples. Additionally, the swelling test indicated a rise in water absorption when the membrane was combined with collagen material

COLLAGEN MATRIX MENISCAL WRAPPING REDUCES CONTACT PRESSURES IN MENISCAL REPAIR: A FINITE ELEMENT ANALYSIS STUDY

AbstractINTRODUCTIONTo preserve knee function and reduce degenerative, meniscal tears should be repaired where possible. Meniscal wrapping with collagen matrices has shown promising clinical outcome (AAOS meniscal algorithm), however there is limited basic science to support this.AIMto model the contact pressures on the human tibial plateau beneath a (1) a repaired radial meniscal tear and (2) a wrapped and repaired radial meniscal tear.METHODOLOGYComplete anterolateral radial tears were formed across 4 lateral human menisci, before repairing with ‘rip-stop’ H sutures using 2mm Arthrex Meniscal Suture tape. This was then repeated with the addition of a ChondroGide collagen matrix wrapping. From this experimental setup a finite element (FE) analysis model was construted.FE models of the two techniques (i) suture alone and (ii) suture and collagen-matrix wrap, were then modelled; bone was linear elastic, articular cartilage was a hyperelastic Yeoh model, and a linear elastic and transversely isotropic material model for the meniscus.The contact areas of the articulating surfaces, meniscus kinematics, and stress distribution around the repair were compared between the two systems.RESULTSMeniscal suture-tape repair had higher local stresses and strains (σ_max=51 MPa ε_max=25%) around the repair compared to with Collagen wrapping (σ_max=36.6MPa ε_max=15%). Radial displacement and pressure on the meniscal contact surfaces were higher in the suture only repair.CONCLUSIONCollagen-matrix wrapping strengthens the repair, reducing local peak stresses and strains around the suture-tape. This could reduce the chance of suture-tape pull-out and subsequent repair failure.

Design matters: A comparison of natural versus synthetic skin substitutes across benchtop and porcine wound healing metrics: An experimental study.

Skin substitutes, essential tools for helping close full thickness wounds with minimal scarring, are available in both collagen-based and synthetic polyurethane constructions. Here we explore fundamental differences between two frequently used skin substitutes and discuss how these differences may impact in vivo performance. Polyurethane- and collagen-based matrices were characterized in vitro for pore size via scanning electron microscopy, hydrophobicity via liquid contact angle, conformability via bending angle, and biocompatibility via fibroblast and keratinocyte adhesion and proliferation. These matrices were then evaluated in a full-thickness excisional pig wound study followed by histological analysis. Statistical analysis was performed using t-tests or one-way analysis of variances with Tukey's multiple post hoc comparisons, where appropriate. Average pore diameter in the tested polyurethane matrix was over four times larger than that of the collagen matrix (589 ± 297 µm vs. 132 ± 91 µm). Through liquid contact angle measurement, the collagen matrix (not measurable) was found to be hydrophilic compared to the hydrophobic polyurethane matrix (>90°). The collagen matrix was significantly more conformable than the polyurethane matrix (9 ± 2° vs. 84 ± 5° bending angle, respectively). Fibroblast and keratinocyte adhesion and proliferation assays elucidated a significantly greater ability of both cell types to attach and proliferate on collagen versus polyurethane. While the porcine study showed minimal contraction of either matrix material, histological findings between the two treatments were markedly different. Collagen matrices were associated with early fibroblast infiltration and fibroplasia, whereas polyurethane matrices elicited a strong multinucleated giant cell response and produced a network of comparatively aligned collagen fibrils. The more favorable in vitro properties of the collagen matrix led to less inflammation and better overall tissue response in vivo. Overall, our findings demonstrate how the choice of biomaterial and its design directly translate to differing in vivo mechanisms of action and overall tissue quality.

Dynamic Tensile Stress Promotes Regeneration of Achilles Tendon in a Panda Rope Bridge Technique Mice Model.

Regeneration of ruptured Achilles tendon remains a clinical challenge owing to its limited regenerative capacity. Dynamic tensile stress plays a positive role in the regeneration of tendon, although the specific underlying mechanisms remain unclear. In this study, the Achilles tendon defect-regeneration model was created in male C57BL/6 mice aged 8weeks. The animals were randomly assigned to four groups-repair, non-repair, repair with fixation, and non-repair with fixation. The repair groupand repair with fixation group adopted the panda rope bridge technique (PRBT) repair method. Our results demonstrated the presence of more densely aligned and mature collagen fibers, as well as more tendon-related makers, in the repair group at both 2- and 4-week post-surgery. Furthermore, the biomechanical strength of the regenerated tendon in the repair group was highly improved. Most importantly, the expressions of integrin αv and its downstream and the phosphorylation levels of FAK and ERK were remarkably higher in the repair group than in the other groups. Furthermore, blocking FAK or ERK with selective inhibitors PF573228 and U0126 resulted in obvious adverse effects on the histological structure of the regenerated Achilles tendon. In summary, this study demonstrated that dynamic tensile stress based on the PRBT could effectively promote the regeneration of the Achilles tendon, suggesting that dynamic tensile stress enhances the cell proliferation and tenogenic differentiation via the activation of the integrin/FAK/ERK signaling pathway.

Fibrotic Diseases of the Human Urinary and Genital Tract: Current Understanding and Potential Strategies for Treatment.

Fibrosis is a disease condition characterized by abnormalities of the extracellular matrix, such as accumulation of the transforming growth factor β, infiltration by myofibroblasts, deposition of collagen, and a generalized dysregulation of collagen maturation. It can severely impair the function of organs by replacing normal tissue with a highly collagenized matrix, thereby reducing the elasticity and compliance of tissues. Fibrotic diseases of the genitourinary tract present relevant problems in healthcare, and their principles of pathophysiology remain unclarified; hence, the armamentarium for prevention and treatment is limited. These diseases include renal fibrosis, Peyronie's disease and ureteral and urethral strictures due to perturbations in the process of wound healing in response to injuries. Such deteriorations may contribute to obstructive uropathies or sexual dysfunction. This review provides a brief overview of the most frequent fibrotic diseases of the genitourinary system and of how the pathophysiology is related to symptoms, and also highlights potential therapeutic strategies to address the abnormal deposition of collagen. Although the understanding of factors associated with fibrotic conditions of the urinary and genital tract is still limited, some beneficial advances have been made. Further research will serve to provide a more comprehensive insight into factors responsible for the development of fibrotic tissue deposition.