Fibrous Capsule Formation Research Articles

Designing injectable dermal matrix hydrogel combined with silver nanoparticles for methicillin-resistant Staphylococcus aureus infected wounds healing

Hydrogel-based delivery systems have now emerged as a pivotal platform for addressing chronic tissue defects, leveraging their innate capacity to suppress pathogenic infections and facilitate expedited tissue regeneration. In this work, an injectable hydrogel dressing, termed AgNPs-dermal matrix hydrogel (Ag@ADMH), has been designed to expedite the healing process of wounds afflicted with methicillin-resistant Staphylococcus aureus (MRSA), featuring sustained antibacterial efficacy. The synthesis of the hydrogel dressing entailed a self-assembly process of collagen fibers within an acellular dermal matrix to construct a three-dimensional scaffold, encapsulated with plant polyphenol-functionalized silver nanoparticles (AgNPs). The Ag@ADMH demonstrated exceptional biocompatibility, and enables a sustained release of AgNPs, ensuring prolonged antimicrobial activity. Moreover, the in vitro RT-qPCR analysis revealed that compared with ADMH, Ag@ADMH diminish the expression of iNOS while augmenting CD206 expression, thereby mitigating the inflammatory response and fostering wound healing. Especially, the Ag@ADMH facilitated a reduction in M1 macrophage polarization, as evidenced by a significant decrement in the M1 polarization trend and an enhanced M2/M1 ratio in dermal matrix hydrogels laden with AgNPs, corroborated by confocal microscopy and flow cytometry analyses of macrophage phenotypes. The in vivo assessments indicated that Ag@ADMH minimized fibrous capsule formation. In a full-thickness skin defect model of MRSA infection, the formulation significantly attenuated the inflammatory response by reducing MPO and CD68 expression levels, concurrently promoting collagen synthesis and CD34 expression, pivotal for vasculogenesis, thereby accelerating the resolution of MRSA-infected wounds. These attributes underscore the injectable extracellular matrix hydrogel as a formidable strategy for the remediation and regeneration of infected wounds.Graphical

Decellularized Amnion Membrane Triggers Macrophage Polarization for Desired Host Immune Response.

Appropriate regulation of immunomodulatory responses, particularly acute inflammation involving macrophages, is crucial for the desired functionality of implants. Decellularized amnion membrane (DAM) is produced by removing cellular components and antigenicity, expected to reduce immunogenicity and the risk of inflammation. Despite the potential of DAM as biomaterial implants, few studies have investigated its specific effects on immunomodulation. Here, it is demonstrated that DAM can regulate macrophage-driven inflammatory response and potential mechanisms are investigated. In vitro results show that DAM significantly inhibits M1 polarization in LPS-induced macrophages by inhibiting Toll-like receptors (TLR) signaling pathway and TNF signaling pathway and promotes macrophage M2 polarization. Physical signals from the 3D micro-structure and the active protein, DCN, binding to key targets may play roles in the process. In the subcutaneous implant model in rats, DAM inhibits the persistence of inflammation and fibrous capsule formation, while promoting M2 macrophage polarization, thereby facilitating tissue regeneration. This study provides insights into DAM's effect and potential mechanisms on the balance of M1/M2 macrophage polarization in vitro and vivo, emphasizing the immunomodulation of ECM-based materials as promising implants.

Preparation and Performance of a Novel Polyurethane Microporous Film on Polypropylene Medical Mesh Surface

This study aims to develop a medical patch surface material featuring a microporous polyurethane (PU) membrane and to assess the material's properties and biological performance. The goal is to enhance the clinical applicability of pelvic floor repair patch materials. PU films with a microporous surface were prepared using PU prepolymer foaming technology. The films were produced by optimizing the PU prepolymer isocyanate index (R value) and the relative humidity (RH) of the foaming environment. The surface morphology of the PU microporous films was observed by scanning electron microscopy, and the chemical properties of the PU microporous films, including hydrophilicity, were analyzed using infrared spectroscopy, Raman spectroscopy, and water contact angle measurements. In vitro evaluations included testing the effects of PU microporous film extracts on the proliferation of L929 mouse fibroblasts and observing the adhesion and morphology of these fibroblasts. Additionally, the effect of the PU microporous films on RAW264.7 mouse macrophages was studied. Immune response and tissue regeneration were assessed in vivo using Sprague Dawley (SD) rats. The PU films exhibited a well-defined and uniform microporous structure when the R value of PU prepolymer=1.5 and the foaming environment RH=70%. The chemical structure of the PU microporous films was not significantly altered compared to the PU films, with a significantly lower water contact angle ([55.7±1.5]° ) compared to PU films ([69.5±1.7]° ) and polypropylene (PP) ([ 104.3±2.5]°), indicating superior hydrophilicity. The extracts from PU microporous films demonstrated good in vitro biocompatibility, promoting the proliferation of L929 mouse fibroblasts. The surface morphology of the PU microporous films facilitated fibroblast adhesion and spreading. The films also inhibited the secretion of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β by RAW264.7 macrophages while enhancing IL-10 and IL-4 secretion. Compared to 24 hours, after 72 hours of culture, the expression levels of TNF-α and IL-1β were reduced in both the PU film and PU microporous film groups and were significantly lower than those in the PP film group (P<0.05), with the most notable decreases observed in the PU microporous film group. IL-10 and IL-4 levels increased significantly in the PU microporous film group, surpassing those in the PP film group (P<0.01), with the most pronounced increase in IL-4. The PU microporous film induced mild inflammation with no significant fibrous capsule formation in vivo. After 60 days of implantation, the film partially degraded, showing extensive collagen fiber growth and muscle formation in its central region. The PU microporous film exhibits good hydrophilicity and biocompatibility. Its surface morphology enhances cell adhesion, regulates the function of RAW264.7 macrophages, and promotes tissue repair, offering new insights for the design of pelvic floor repair and reconstruction patch materials.

In Vivo Release of Zafirlukast from Electrospun Polyisobutylene-Based Fiber Mats to Reduce Capsular Contracture of Silicone Breast Prostheses.

Silicone rubber tissue expanders and breast implants are associated with chronic inflammation, leading to the formation of fibrous capsules. If the inflammation is left untreated, the fibrous capsules can become hard and brittle and lead to formation of capsular contracture. When capsular contracture occurs, implant failure and reoperation is unavoidable. Fibrous capsule formation to medical grade silicone rubber breast implants and polyisobutylene-based electrospun fiber mats attached to silicone rubber with and without an anti-inflammatory therapeutic were compared. A linear polyisobutylene (PIB)-based thermoplastic elastomer is currently applied as a polymer coating for drug release on coronary stents to reduce restenosis. Recent work has created a drug releasing electrospun fiber mat from PIB-based materials. Important to this study, poly(alloocimene-b-isobutylene-b-alloocimene) (AIBA) was electrospun with zafirlukast (ZAF). ZAF is an anti-inflammatory drug that is able to reduce capsule formation and complications to silicone breast implants. Fiber mats are advantageous for local drug delivery because of their high porosity and surface area for drug release. The chief hypothesis was that local release of ZAF from AIBA would lower inflammatory signaling and resulting capsular formation after 90 days in vivo. Electrospun AIBA mats locally released ZAF, lowering inflammation and fibrous capsule development compared to medical grade silicone rubber. Locally and orally released ZAF led to similar results, but the former had much lower concentration that highlights local delivery's therapeutic potential. Released ZAF from AIBA fiber mats mitigated inflammation and serves as an alternative to existing clinical approaches.

Adhesive anti-fibrotic interfaces on diverse organs

Implanted biomaterials and devices face compromised functionality and efficacy in the long term owing to foreign body reactions and subsequent formation of fibrous capsules at the implant–tissue interfaces1–4. Here we demonstrate that an adhesive implant–tissue interface can mitigate fibrous capsule formation in diverse animal models, including rats, mice, humanized mice and pigs, by reducing the level of infiltration of inflammatory cells into the adhesive implant–tissue interface compared to the non-adhesive implant–tissue interface. Histological analysis shows that the adhesive implant–tissue interface does not form observable fibrous capsules on diverse organs, including the abdominal wall, colon, stomach, lung and heart, over 12 weeks in vivo. In vitro protein adsorption, multiplex Luminex assays, quantitative PCR, immunofluorescence analysis and RNA sequencing are additionally carried out to validate the hypothesis. We further demonstrate long-term bidirectional electrical communication enabled by implantable electrodes with an adhesive interface over 12 weeks in a rat model in vivo. These findings may offer a promising strategy for long-term anti-fibrotic implant–tissue interfaces.

Silicone implant surface microtopography modulates inflammation and tissue repair in capsular fibrosis.

Excessive fibrous capsule formation around silicone mammary implants (SMI) involves immune reactions to silicone. Capsular fibrosis, a common SMI complication linked to host responses, worsens with specific implant topographies. Our study with 10 patients investigated intra- and inter-individually, reduced surface roughness effects on disease progression, wound responses, chronic inflammation, and capsular composition. The results illuminate the significant impact of surface roughness on acute inflammatory responses, fibrinogen accumulation, and the subsequent fibrotic cascade. The reduction of surface roughness to an average roughness of 4 μm emerges as a promising approach for mitigating detrimental immune reactions, promoting healthy wound healing, and curbing excessive fibrosis. The identified proteins adhering to rougher surfaces shed light on potential mediators of pro-inflammatory and pro-fibrotic processes, further emphasizing the need for meticulous consideration of surface design. The composition of the implant capsule and the discovery of intracapsular HSP60 expression highlight the intricate web of stress responses and immune activation that can impact long-term tissue outcomes.

Microstructural and micromechanical characteristics of composite osteoconductive coatings deposited by the atmospheric pressure plasma technique.

Long-term placement of facial implants requires avoiding the formation of fibrous tissue capsules around the artificial material by creating osteoconductive properties of the surface. Most promising approach is the deposition coatings made of materials very similar to bone mineral components, that is, calcium phosphates such as hydroxyapatite (HAp). As part of the research work, an innovative, cost-effective atmospheric pressure plasma deposition (APPD) system was used as a low-temperature coating technology for generating the HAp coatings deposition. Full microstructural characterisation of the coatings using SEM and TEM techniques was carried out in the work. It has been shown that the fully crystalline HAp powder undergoes a transformation during the coatings deposition and the material had a quasi-sintered structure after deposition. The crystalline phase content increased at the coating/substrate interface, while the surface of the HAp was amorphous. This is a very beneficial phenomenon due to the process of bioresorption. The amorphous phase undergoes much faster biodegradation than the crystalline one. In order to increase the bioactivity of the HAp, Zn particles were introduced on the surface of the coating. The TEM microstructural analysis in conjunction with the qualitative analysis of the EDS chemical composition showed that the binding of the Zn particles within the HAp matrix had diffusive character, which is very favourable from the point of view of the quality of the adhesion and the bioactivity of the coating. In the case of such a complex structure and due to its very porous nature, micromechanical analysis was carried out in situ in SEM, that is, by microhardness measurements of both the HAp matrix and the Zn particle. It was shown that the average value of HAp microhardness was 4.395GPa ± 0.08, while the average value of Zn microhardness was 1.142GPa ± 0.02.

Polyetheretherketone surface modification by lithium-doped bioglass nanospheres to regulate bone immunity and promote osseointegration

Polyetheretherketone (PEEK) is a frequently utilized orthopedic implant material in clinical settings. However, the adverse inflammatory and immunological reactions due to the PEEK surface after implantation often cause poor osseointegration and thereby hinder its clinical utility. To improve osseointegration and enhance the success rate of PEEK implants, the surface can be biofunctionalized to be immunomodulatory. Consequently, in this study, lithium-doped bioglass nanospheres (Li/BGs) was coated on the sulfonated PEEK surface. Furthermore, we assessed the anti-inflammatory potential of the biofunctionalized PEEK implants and their impact on osteogenesis. In our study, it was observed that the in vitro biofunctionalized PEEK surface exhibited enhanced osteogenesis and immunomodulatory osteogenesis properties, while also effectively suppressing the acute inflammatory response initiated by macrophages. Furthermore, our in vivo experiments demonstrated that the biofunctionalized PEEK surface contributed to improved osteogenesis properties and mitigated the formation of fibrous capsules. Therefore, the in vitro and in vivo results demonstrated that PEEK surface modification with Li/BGs not only changed the disadvantage of being bioinert on the surface but also endowed it with osteoimmunomodulatory regulation and bone-promoting properties. Thus, the biofunctionalized PEEK may be a promising candidate for use as an orthopedic implant in clinical settings.

3D-PRINTED HYBRID SCAFFOLDS FOR CARTILAGE REGENERATION

For chondral damage in younger patients, surgical best practice is microfracture, which involves drilling into the bone to liberate the bone marrow. This leads to a mechanically inferior fibrocartilage formed over the defect as opposed to the desired hyaline cartilage that properly withstands joint loading. While some devices have been developed to aid microfracture and enable its use in larger defects, fibrocartilage is still produced and there is no clear clinical improvement over microfracture alone in the long term. Our goal is to develop 3D printed devices, which surgeons can implant with a minimally invasive technique. The scaffolds should match the functional properties of cartilage and expose endogenous marrow cells to suitable mechanobiological stimuli in-situ, in order to promote healing of articular cartilage lesions before they progress to osteoarthritis, and rapidly restore joint health and mobility. Importantly, scaffolds should direct a physiological host reaction, instead of a foreign body reaction, associated with chronic inflammation and fibrous capsule formation, negatively influencing the regenerative outcome.Our novel silica/polytetrahydrofuran/polycaprolactone hybrids were prepared by sol-gel synthesis and scaffolds were 3D printed by direct ink writing. 3D printed hybrid scaffolds with pore channels of ~250 µm mimic the compressive behaviour of cartilage. Our results show that these scaffolds support human bone marrow stem/stromal cell (hMSC) differentiation towards chondrogenesis in vitro under hypoxic conditions to produce markers integral to articular cartilage-like matrix evaluated by immunostaining and gene expression analysis. Macroscopic and microscopic evaluation of subcutaneously implanted scaffolds in mice showed that scaffolds caused a minimal resolving inflammatory response. Our findings show that 3D printed hybrid scaffolds have the potential to support cartilage regeneration.Acknowledgements: Authors acknowledge funding provided by EPSRC grant EP/N025059/1.

Exploring therapy transport from implantable medical devices using experimentally informed computational methods.

Implantable medical devices that can facilitate therapy transport to localized sites are being developed for a number of diverse applications, including the treatment of diseases such as diabetes and cancer, and tissue regeneration after myocardial infraction. These implants can take the form of an encapsulation device which encases therapy in the form of drugs, proteins, cells, and bioactive agents, in semi-permeable membranes. Such implants have shown some success but the nature of these devices pose a barrier to the diffusion of vital factors, which is further exacerbated upon implantation due to the foreign body response (FBR). The FBR results in the formation of a dense hypo-permeable fibrous capsule around devices and is a leading cause of failure in many implantable technologies. One potential method for overcoming this diffusion barrier and enhancing therapy transport from the device is to incorporate local fluid flow. In this work, we used experimentally informed inputs to characterize the change in the fibrous capsule over time and quantified how this impacts therapy release from a device using computational methods. Insulin was used as a representative therapy as encapsulation devices for Type 1 diabetes are among the most-well characterised. We then explored how local fluid flow may be used to counteract these diffusion barriers, as well as how a more practical pulsatile flow regimen could be implemented to achieve similar results to continuous fluid flow. The generated model is a versatile tool toward informing future device design through its ability to capture the expected decrease in insulin release over time resulting from the FBR and investigate potential methods to overcome these effects.

Guided bone regeneration in long-bone defect with a bilayer mineralized collagen membrane

Bone regeneration for large, critical-sized bone defects remains a clinical challenge nowadays. Guided bone regeneration (GBR) is a promising technique for the repair of multiple bone defects, which is widely used in oral and maxillofacial bone defects but is still unsatisfied in the treatment of long bone defects. Here, we successfully fabricated a bilayer mineralized collagen/collagen (MC/Col)-GBR membrane with excellent osteoinductive and barrier function by coating the MC particles prepared via in situ biomimetic mineralization process on one side of a sheet-like pure collagen layer. The aim of the present study was to investigate the physicochemical properties and biological functions of the MC/Col film, and to further evaluate its bone regeneration efficiency in large bone defect repair. Fourier-transform infrared spectra and X-ray diffraction patterns confirmed the presence of both hydroxyapatite and collagen phase in the MC/Col film, as well as the chemical interaction between them. stereo microscope, scanning electron microscopy and atomic force microscope showed the uniform distribution of MC particles in the MC/Col film, resulting in a rougher surface compared to the pure Col film. The quantitative analysis of surface contact angle, light transmittance and tensile strength demonstrated that the MC/Col film have better hydrophilicity, mechanical properties, light-barrier properties, respectively. In vitro macrophage co-culture experiments showed that the MC/Col film can effectively inhibit macrophage proliferation and fusion, reducing fibrous capsule formation. In vivo bone repair assessment of a rabbit critical segmental radial defect proved that the MC/Col film performed better than other groups in promoting bone repair and regeneration due to their unique dual osteoinductive/barrier function. These findings provided evidence that MC/Col film has a great clinical potential for effective bone defect repair.Graphic abstract

Surface Topography of PLA Implants Defines the Outcome of Foreign Body Reaction: An In Vivo Study.

The formation of a dense fibrous capsule around the foreign body and its contracture is the most common complication of biomaterial implantation. The aim of our research is to find out how the surface of the implant influences the inflammatory and fibrotic reactions in the surrounding tissues. We made three types of implants with a remote surface topography formed of polylactide granules with different diameters: large (100-200 µm), medium (56-100 µm) and small (1-56 µm). We placed these implants in skin pockets in the ears of six chinchilla rabbits. We explanted the implants on the 7th, 14th, 30th and 60th days and performed optical coherence tomography, and histological, immunohistochemical and morphometric studies. We examined 72 samples and compared the composition of immune cell infiltration, vascularization, the thickness of the peri-implant tissues, the severity of fibrotic processes and α-SMA expression in myofibroblasts. We analyzed the scattering coefficient of tissue layers on OCT scans. We found that implants made from large granules induced a milder inflammatory process and slower formation of a connective tissue capsule around the foreign body. Our results prove the importance of assessing the surface texture in order to avoid the formation of capsular contracture after implantation.

Latest advances: Improving the anti-inflammatory and immunomodulatory properties of PEEK materials.

Excellent biocompatibility, mechanical properties, chemical stability, and elastic modulus close to bone tissue make polyetheretherketone (PEEK) a promising orthopedic implant material. However, biological inertness has hindered the clinical applications of PEEK. The immune responses and inflammatory reactions after implantation would interfere with the osteogenic process. Eventually, the proliferation of fibrous tissue and the formation of fibrous capsules would result in a loose connection between PEEK and bone, leading to implantation failure. Previous studies focused on improving the osteogenic properties and antibacterial ability of PEEK with various modification techniques. However, few studies have been conducted on the immunomodulatory capacity of PEEK. New clinical applications and advances in processing technology, research, and reports on the immunomodulatory capacity of PEEK have received increasing attention in recent years. Researchers have designed numerous modification techniques, including drug delivery systems, surface chemical modifications, and surface porous treatments, to modulate the post-implantation immune response to address the regulatory factors of the mechanism. These studies provide essential ideas and technical preconditions for the development and research of the next generation of PEEK biological implant materials. This paper summarizes the mechanism by which the immune response after PEEK implantation leads to fibrous capsule formation; it also focuses on modification techniques to improve the anti-inflammatory and immunomodulatory abilities of PEEK. We also discuss the limitations of the existing modification techniques and present the corresponding future perspectives.

Evaluation of new robust silk fibroin hydrogels for posterior scleral reinforcement in rabbits.

Background: Currently, there is no ideal material available for posterior scleral reinforcement (PSR) to prevent the progression of high myopia. In this study, we investigated robust regenerated silk fibroin (RSF) hydrogels as potential grafts for PSR in animal experiments to evaluate their safety and biological reactions. Methods: PSR surgery was performed on the right eye of twenty-eight adult New Zealand white rabbits, with the left eye serving as a self-control. Ten rabbits were observed for 3 months, while 18 rabbits were observed for 6 months. The rabbits were evaluated using intraocular pressure (IOP), anterior segment and fundus photography, A- and B-ultrasound, optical coherence tomography (OCT), histology, and biomechanical tests. Results: No complications such as significant IOP fluctuation, anterior chamber inflammation, vitreous opacity, retinal lesion, infection, or material exposure were observed. Furthermore, no evidence of pathological changes in the optic nerve and retina, or structural abnormalities on OCT, were found. The RSF grafts were appropriately located at the posterior sclera and enclosed in fibrous capsules. The scleral thickness and collagen fiber content of the treated eyes increased after surgery. The ultimate stress of the reinforced sclera increased by 30.7%, and the elastic modulus increased by 33.0% compared to those of the control eyes at 6months after surgery. Conclusion: Robust RSF hydrogels exhibited good biocompatibility and promoted the formation of fibrous capsules at the posterior sclera in vivo. The biomechanical properties of the reinforced sclera were strengthened. These findings suggest that RSF hydrogel is a potential material for PSR.

Electrospun fiber-based strategies for controlling early innate immune cell responses: Towards immunomodulatory mesh designs that facilitate robust tissue repair.

Electrospun fibrous meshes are widely used for tissue repair due to their ability to guide a host of cell responses including phenotypic differentiation and tissue maturation. A critical factor determining the eventual biological outcomes of mesh-based regeneration strategies is the early innate immune response following implantation. The natural healing process involves a sequence of tightly regulated, temporally varying and delicately balanced pro-/anti-inflammatory events which together promote mesh integration with host tissue. Matrix designs that do not account for the immune milieu can result in dysregulation, chronic inflammation and fibrous capsule formation, thus obliterating potential therapeutic outcomes. In this review, we provide systematic insights into the effects of specific fiber/mesh properties and mechanical stimulation on the responses of early innate immune modulators viz., neutrophils, monocytes and macrophages. We identify matrix characteristics that promote anti-inflammatory immune phenotypes, and we correlate such responses with pro-regenerative in vivo outcomes. We also discuss recent advances in 3D fabrication technologies, bioactive functionalization approaches and biomimetic/bioinspired immunomodulatory mesh design strategies for tissue repair and wound healing. The mechanobiological insights and immunoregulatory strategies discussed herein can help improve the translational outcomes of fiber-based regeneration. STATEMENT OF SIGNIFICANCE: The crucial role played by immune cells in promoting biomaterial-based tissue regeneration is being increasingly recognized. In this review focusing on the interactions of innate immune cells with electrospun fibrous meshes, we systematically elucidate the effects of the fiber microenvironment and mechanical stimulation on biological responses, and build upon these insights to inform the rational design of immunomodulatory meshes for effective tissue repair. We discuss state-of-the-art fabrication methods and mechanobiological advances that permit the orchestration of temporally controlled phenotypic switches in immune cells during different phases of healing. The design strategies discussed herein can also be leveraged to target several complex autoimmune and inflammatory diseases.

Epsin Mimetic UPI Peptide Delivery Strategies to Improve Endothelization of Vascular Grafts.

Endothelialization of engineered vascular grafts for replacement of small-diameter coronary arteries remains a critical challenge. The ability for an acellular vascular graft to promote endothelial cell (EC) recruitment in the body would be very beneficial. This study investigated epsins as a target since they are involved in internalization of vascular endothelial growth factor receptor 2. Specifically, epsin-mimetic UPI peptides are delivered locally from vascular grafts to block epsin activity and promote endothelialization. The peptide delivery from fibrin coatings allowed for controlled loading and provided a significant improvement in EC attachment, migration, and growth in vitro. The peptides have even more important impacts after grafting into rat abdominal aortae. The peptides prevented graft thrombosis and failure that is observed with a fibrin coating alone. They also modulated the in vivo remodeling. The grafts are able to remodel without the formation of a thick fibrous capsule on the adventitia with the 100µgmL-1 peptide-loaded condition, and this condition enabled the formation of a functional EC monolayer in the graft lumen after only 1 week. Overall, this study demonstrated that the local delivery of UPI peptides is a promising strategy to improve the performance of vascular grafts.

Biphasic Interpositional Allograft for Rotator Cuff Repair Augmentation Is Safe in an Ovine Model

This study is a preclinical histological assessment of a biphasic acellular interpositional cancellous allograft in an ovine model of rotator cuff repair (RCR) designed to better understand its safety profile and effects on tendon healing after rotator cuff repair. Thirty skeletally mature sheep with clinically normal shoulders with an artificially created degenerative infraspinatus tendon (IST) tear were randomized to control and treatment groups. Animals were euthanized at 3-weeks, 6-weeks, and 12-weeks. After gross dissection, rotator cuff specimens were fixed with formalin and polymerized for sectioning and staining. Blinded histological scores evaluated inflammatory cell infiltrates, signs of degradation, particulate debris, collagen arrangement, neo-vascularization, and enthesis qualitative measures. There were no treatment specimens that exhibited histological signs of a significant infection, inflammatory infiltrate, or foreign body reaction such as granuloma or fibrous capsule formation. Histological scores in all categories were not significantly different at all time points, including the primary endpoint mean cumulative inflammatory score (control: 3.66 ± 1.21 versus treated: 4.33 ± 1.51, p = 0.42), when comparing the treatment and control RCR groups. In general, the degree of tendon healing and host tissue response was essentially equivalent between the two groups with observation of low overall levels of inflammation and progressive improvements in collagen organization, reduced tenocyte activity, and fibrocartilaginous enthesis reformation. This histological study demonstrated the use of a biphasic interpositional allograft for rotator cuff repair augmentation in an ovine model does not generate an inflammatory response or foreign body reaction. Use of the biphasic interpositional allograft resulted in a histological profile that was essentially equivalent to that of a standard RCR at 3-, 6-, and 12-week post-operative timepoints. These findings suggest that a biphasic interpositional allograft is safe for further clinical investigation in humans before broader clinical application. Patch augmentation of RCR is a popular technique that has shown clinical success in improving the likelihood of a successful repair in patients at elevated risk for retear. Newer augmentation technologies are being developed to address the biology at the interface between the bone and soft tissue where failure typically occurs.

Quantitative Proteomic Characterization of Foreign Body Response towards Silicone Breast Implants Identifies Chronological Disease-Relevant Biomarker Dynamics.

The etiology of exaggerated fibrous capsule formation around silicone mammary implants (SMI) is multifactorial but primarily induced by immune mechanisms towards the foreign material silicone. The aim of this work was to understand the disease progression from implant insertion and immediate tissue damage response reflected in (a) the acute wound proteome and (b) the adsorption of chronic inflammatory wound proteins at implant surfaces. An intraindividual relative quantitation TMT-liquid chromatography-tandem mass spectrometry approach was applied to the profile wound proteome formed around SMI in the first five days post-implantation. Compared to plasma, the acute wound profile resembled a more complex composition comprising plasma-derived and locally differentially expressed proteins (DEPs). DEPs were subjected to a functional enrichment analysis, which revealed the dysregulation of signaling pathways mainly involved in immediate inflammation response and ECM turnover. Moreover, we found time-course variations in protein enrichment immediately post-implantation, which were adsorbed to SMI surfaces after 6-8 months. Characterization of the expander-adhesive proteome by a label-free approach uncovered a long-term adsorbed acute wound and the fibrosis-associated proteome. Our findings propose a wound biomarker panel for the early detection and diagnosis of excessive fibrosis that could potentially broaden insights into the characteristics of fibrotic implant encapsulation.

Effect of Alleviating Fibrosis with EGCG-Modified Bone Graft in Murine Model Depended on Less Accumulation of Inflammatory Macrophage.

In response to current trends in the modification of guided bone regeneration (GBR) materials, we aimed to build upon our previous studies on epigallocatechin-3-gallate (EGCG) by immersing a commonly used bone graft primarily composed of hydroxyapatite (HA) in EGCG solution, expecting to obtain superior bone material integration after implantation. Bone grafts are commonly used for bone repair, in which the bone extracellular matrix is stimulated to promote osteogenesis. However, due to its profibrosis effect, this osteoconductive material commonly exhibits implant failure. In addition to providing a basic release profile of EGCG-modified bone graft (E-HA) to clarify the relationship between this material and the environment, we have examined the integration effect via subcutaneous implantation experiments. In this manner, we have assessed the aggregation of proinflammatory macrophages, the formation of fibrous capsules, and an enhanced cell viability observed in cultured RAW 264.7 cells. Among these results, we focus on proinflammatory macrophages due to their close relationship with fibrosis, which is the most important process in the immune response. Immunofluorescent staining results showed that E-HA substantially compromised the formation of fibrous capsules in hematoxylin-eosin-stained sections, which exhibited less proinflammatory macrophage recruitment; meanwhile, the cell viability was improved. This work lays the foundation for future studies on GBR.

Tuning foreign body response with tailor-engineered nanoscale surface modifications: fundamentals to clinical applications.

Biomaterials are omnipresent in today's healthcare services and are employed in various applications, including implants, sensors, healthcare accessories, and drug delivery systems. Unfavorable host immunological responses frequently jeopardize the efficacy of biomaterials. As a result, surface modification has received much attention in controlling inflammatory responses since it helps camouflage the biomaterial from the host immune system, influencing the foreign body response (FBR) from protein adsorption to fibrous capsule formation. Surfaces with controlled nanotopography and chemistry, among other surface modification methodologies, have effectively altered the immune response to biomaterials. However, the field is still in its early stages, with only a few studies showing a synergistic effect of surface chemistry and nanotopography on inflammatory and wound healing pathways. Therefore, this review will concentrate on the individual and synergistic effects of surface chemistry and nanotopography on FBR modulation and the molecular processes known to modulate these responses. This review will also provide insights into crucial research gaps and advancements in various tactics for modulating FBR, opening new paths for future research. This will further aid in improving our understanding of the immune response to biomaterials, developing advanced surface modification techniques, designing immunomodulatory biomaterials, and translating discoveries into clinical applications.