Fibrous Encapsulation Research Articles

Prodrug inspired bi-layered electrospun membrane with properties of enhanced tissue integration for guided tissue regeneration.

Guided tissue regeneration (GTR) membranes play a vital role in periodontal surgery. Recently a series of composite electrospun membranes have been fabricated to improve the unexpected biodegradation of collagen-based GTR membranes. However, their tissue integrity needs to be studied in depth. In this study, a bi-layered electrospun membrane (BEM) inspired by "prodrug" was fabricated, which contained a dense-layer (BEM-DL) and a potential loose-layer (BEM-LL). The nanofibers of BEM-DL were composed of poly(l-lactic-co-glycolic acid) and tilapia skin collagen (TSC). Whereas the BEM-LL consisted of two types of nanofibers, one was the same as BEM-DL and the other was made from TSC. The morphology, degradation in vitro, cytocompatibility and biocompatibility in rats were investigated with a poly(lactic-co-glycolic acid) electrospun membrane (PLGA) as the negative control. The pore size of BEM-LL soaked for 7days became larger than the original sample (164.8±90.9 and 52.5±21.0μm2 , respectively), which was significantly higher (p<.05) than that of BEM-DL and PLGA. The BEM-LL displayed a larger weight loss rate of 82.3±3.6% than the BEM-DL of 46.0±2.8% at day 7 because of the rapid degradation of TSC fibers. The cytocompatibility test demonstrated that L929 cells were only spread on the surface of the BEM-DL while MC3T3-E1 cells grew into the BEM-LL layer. The subcutaneous implantation test further proved that BEM-DL performed as a cellular barrier, whereas BEM-LL was conducive to cell infiltration as deep as 200μm with reduced fibrous encapsulation. Herein, the BEM inspired by "prodrug" is a promising GTR membrane with a property of enhanced tissue integration.

Medical Applications of Porous Biomaterials: Features of Porosity and Tissue-Specific Implications for Biocompatibility.

Porosity is an important material feature commonly employed in implants and tissue scaffolds. The presence of material voids permits the infiltration of cells, mechanical compliance, and outward diffusion of pharmaceutical agents. Various studies have confirmed that porosity indeed promotes favorable tissue responses, including minimal fibrous encapsulation during the foreign body reaction (FBR). However, increased biofilm formation and calcification is also described to arise due to biomaterial porosity. Additionally, the relevance of host responses like the FBR, infection, calcification, and thrombosis are dependent on tissue location and specific tissue microenvironment. In this review, the features of porous materials and the implications of porosity in the context of medical devices is discussed. Common methods to create porous materials are also discussed, as well as the parameters that are used to tune pore features. Responses toward porous biomaterials are also reviewed, including the various stages of the FBR, hemocompatibility, biofilm formation, and calcification. Finally, these host responses are considered in tissue specific locations including the subcutis, bone, cardiovascular system, brain, eye, and female reproductive tract. The effects of porosity across the various tissues of the body is highlighted and the need to consider the tissue context when engineering biomaterials is emphasized.

Polyetheretherketone fibers woven fabrics coated nanostructured silicon nitride and load EGCG as artificial ligaments for promoting ligament-bone integration

Design of an artificial ligament with osteogenic activity to promote ligament-bone integration for anterior cruciate ligament (ACL) reconstruction remains a huge challenge. In this work, polyetheretherketone fibers with nanostructured silicon nitride coating (PSN) and loading epigallocatechin gallate (EGCG) were woven into fabrics (PSN@EG) for artificial ligament application.The in vitro experiments confirmed that PSN@EG significantly upregulated M2 macrophage polarization that promoted secretory of anti-inflammatory cytokines while downregulated M1 macrophage polarization that inhibithed secretory of pro-inflammatory cytokines. Moreover, PSN@EG remarkably improved osteoblastic differentiation of rat bone marrow mesenchymal stem cells (BMSC) while suppressed osteoclastic differentiation of rat bone marrow-derived macrophages (BMM) in macrophage condition medium. The in vivo experiments revealed that PSN@EG promoted new bone formation for ligament-bone integration that inhibited fibrous encapsulation formation. It could be suggested that the synergistic effects of the optimized surface charactieristics (e.g., nano-micro topography), and sustained release of Si ions and EGCG caused the immunomodulatory of PSN@EG, which improved pro-osteogenic macrophage polarization that provided a favorable anti-inflammatory immune environment for enhancing osteogenesis while inhibiting osteoclastogenesis. In summary, PSN@EG with immunomodulatory significantly promoted osteoblastic differentiation while suppressed osteoclastic differentiation, thereby facilitating osteogenesis for ligament-bone integration. As a novel artificial ligament, PSN@EG has tremendous potential for ACL reconstruction.

Effect of plasma ion immersion implantation on physiochemical and biological properties of silk towards creating a versatile biomaterial platform

Silk biomaterials are widely used in tissue engineering applications due to their mechanical tuneability, processability and low immunogenic response. However, due to the lack of cell binding sites, further modification is typically required to optimize silk biomaterials towards a specific biomedical application. Plasma immersion ion implantation (PIII) is a surface modification technique that can covalently attach a wide range of bioactive molecules onto silk surfaces to trigger desirable biological responses. However, the effect of PIII treatment on the surface and bulk properties of silk biomaterials remains largely unknown. Therefore, the aim of this study is to investigate PIII-treated silk (PIII-silk) biomaterials towards their use as a platform for biomedical applications. Silk films with or without PIII treatment were examined to determine changes to the surface and bulk properties, including the chemical, mechanical, degradation properties, and the in vivo immune response. PIII treatment of silk was found to alter surface chemistry with densification of the silk surface layer and the introduction of oxygen and nitrogen functional groups. This then resulted in a significant increase in surface stiffness but also led to minor changes in tensile properties of clinically relevant silk formats and minor differences in in vitro degradation properties. Following PIII treatment, there was a significant increase in HCAEC adhesion on PIII-silk compared to untreated silk but no significant differences in fibrous encapsulation and macrophage response when implanted in vivo in a subcutaneous mouse model. Together, these results show that PIII treatment of silk minimally compromises the bulk properties and can be used to promote cellular interactions as well as a means of reagent-free, covalent immobilization of biomolecules.

Bioadhesive and conductive hydrogel-integrated brain-machine interfaces for conformal and immune-evasive contact with brain tissue

•BMI is obtained by a self-setting process of hydrogel on microelectrode array •The hydrogel is bioadhesive, ensuring seamless contact with brain tissue •The hydrogel is ultrasoft, being mechanically compatible with soft brain tissues •The hydrogel is immune-evasive, being suitable for long-term implantable BMI Brain-machine interfaces (BMIs) enable communication between the brain and external machines. However, mechanical and biological mismatches, as well as weak physical adhesion-induced shifts between rigid electronic devices and soft brain tissue, generally trigger a host immune response, affecting signal recording and reducing the lifespan of BMIs in clinics. Herein, we design a bioadhesive ultrasoft BMI based on integration of bioelectronics with a dopamine methacrylate-hybridized poly(3,4-ethylenedioxythiophene) nanoparticle (dPEDOT NP)-incorporated hydrogel with high conductivity. The hydrogel exhibits robust adhesiveness, enabling tight integration with metallic microcircuits and seamless adhesion to the brain tissue. Most importantly, the hydrogel exhibits a brain-level modulus that reduces its mechanical discrepancy with brain tissue. Meanwhile, the hydrogel possesses immune-evasive ability, which actively prevents fibrous tissue encapsulation and neuroinflammation after implantation. Consequently, the immune-evasive, bioadhesive, ultrasoft, and conductive hydrogel-integrated BMI permits long-term and accurate electroencephalographic signal acquisition and communication with minimal foreign body reaction. Brain-machine interfaces (BMIs) enable communication between the brain and external machines. However, mechanical and biological mismatches, as well as weak physical adhesion-induced shifts between rigid electronic devices and soft brain tissue, generally trigger a host immune response, affecting signal recording and reducing the lifespan of BMIs in clinics. Herein, we design a bioadhesive ultrasoft BMI based on integration of bioelectronics with a dopamine methacrylate-hybridized poly(3,4-ethylenedioxythiophene) nanoparticle (dPEDOT NP)-incorporated hydrogel with high conductivity. The hydrogel exhibits robust adhesiveness, enabling tight integration with metallic microcircuits and seamless adhesion to the brain tissue. Most importantly, the hydrogel exhibits a brain-level modulus that reduces its mechanical discrepancy with brain tissue. Meanwhile, the hydrogel possesses immune-evasive ability, which actively prevents fibrous tissue encapsulation and neuroinflammation after implantation. Consequently, the immune-evasive, bioadhesive, ultrasoft, and conductive hydrogel-integrated BMI permits long-term and accurate electroencephalographic signal acquisition and communication with minimal foreign body reaction.

Advantages of decellularized bovine pericardial scaffolds compared to glutaraldehyde fixed bovine pericardial patches demonstrated in a 180-day implant ovine study.

Glutaraldehyde (GA)-fixed bovine pericardial patches remain the cardiovascular industry standard despite reports of degradation, thickening, inflammation, calcification and lack of tissue remodelling. Decellularization provides the opportunity to attenuate some of these immune-mediated processes. This study compared the mechanical and morphological integrity of bovine pericardium that is GA-fixated (Glycar® patches) or decellularized (BPS), using a proprietary protocol, following implantation in an ovine model. The impact of the processing methods on tissue strength and morphology was assessed prior to implantation. Pericardial patches were then implanted in the descending aorta and main pulmonary artery of juvenile sheep (n = 6 per group) for 180days, and clinically evaluated using echocardiography. At explanation, patches were evaluated for strength, calcification and biological interaction. Histology demonstrated a wave-like appearance of well-separated collagen fibers for BPS scaffolds that provided pore sizes adequate to promote fibroblast infiltration. The collagen of the Glycar® patches showed loss of collagen fiber integrity, making the collagen densely compacted, contributing to insignificant recipient cell infiltration. The clinical performance of both groups was excellent, and echocardiography confirmed the absence of aneurysm formation, calcification and degeneration. Explanted Glycar® patches demonstrated cells in abundance within the fibrous encapsulation that separated the implant from the host tissue. More importantly, the fibrous encapsulation also contributed to patch thickening of both the explanted aorta and pulmonary patches. The decellularized pericardial scaffolds demonstrated recellularization, resistance to calcification, re-endothelialization and adequate strength after 180-day implantation. The proprietary decellularization protocol produced pericardial scaffolds that could be considered as an alternative to GA-fixed pericardial patches.

Mapping Macrophage Polarization and Origin during the Progression of the Foreign Body Response to a Poly(ethylene glycol) Hydrogel Implant.

Poly(ethylene glycol) (PEG) hydrogels hold promise for in vivo applications but induce a foreign body response (FBR). While macrophages are key in the FBR, many questions remain. This study investigates temporal changes in the transcriptome of implant-associated monocytes and macrophages. Proinflammatory pathways are upregulated in monocytes compared to control monocytes but subside by day 28. Macrophages are initially proinflammatory but shift to a profibrotic state by day 14, coinciding with fibrous capsule emergence. Next, this study assesses the origin of macrophages responsible for fibrous encapsulation using wildtype, C-C Motif Chemokine Receptor 2 (CCR2)-/- mice that lack recruited macrophages, and Macrophage Fas-Induced Apoptosis (MaFIA) mice that enable macrophage ablation. Subpopulations of recruited and tissue-resident macrophages are identified. Fibrous encapsulation proceeds in CCR2-/- mice similar to wildtype mice. However, studies in MaFIA mice indicate that macrophages are necessary for fibrous capsule formation. These findings suggest that macrophage origin impacts the FBR progression and provides evidence that tissue-resident macrophages and not the recruited macrophages may drive fibrosis in the FBR to PEG hydrogels. This study demonstrates that implant-associated monocytes and macrophages have temporally distinct transcriptomes in the FBR and that profibrotic pathways associated with macrophages may be enriched in tissue-resident macrophages.

Stress Corrosion Analysis and Direct Cell Viability of Biodegradable Zn-Fe-Ca Alloy in In-Vitro Conditions

Due to the excellent biocompatibility of Zn and Zn-based alloys, researchers have shown great interest in developing biodegradable implants based on zinc. Furthermore, zinc is an essential component of many enzymes and proteins. The human body requires ~15 mg of Zn per day, and there is minimal concern for systemic toxicity from a small zinc-based cardiovascular implant, such as an arterial stent. However, biodegradable Zn-based implants have been shown to provoke local fibrous encapsulation reactions that may isolate the implant from its surrounding environment and interfere with implant function. The development of biodegradable implants made from Zn-Fe-Ca alloy was designed to overcome the problem of fibrous encapsulation. In a previous study made by the authors, the Zn-Fe-Ca system demonstrated a suitable corrosion rate that was higher than that of pure Zn and Zn-Fe alloy. The Zn-Fe-Ca system also showed adequate mechanical properties and a unique microstructure that contained a secondary Ca-reach phase. This has raised the promise that the tested alloy could serve as a biodegradable implant metal. The present study was conducted to further evaluate this promising Zn alloy. Here, we assessed the material’s corrosion performance in terms of cyclic potentiodynamic polarization analysis and stress corrosion behavior in terms of slow strain rate testing (SSRT). We also assessed the ability of cells to survive on the alloy surface by direct cell culture test. The results indicate that the alloy develops pitting corrosion, but not stress corrosion under phosphate-buffered saline (PBS) and air environment. The direct cell viability test demonstrates the successful adherence and growth of cells on the alloy surface.

O46 SUTURABLE MESH IMPROVES OUTCOMES FOR LAPAROTOMY CLOSURE IN COMPARISON TO POLYPROPYLENE SUTURE IN A REALISTIC PORCINE MODEL

Abstract Aim Laparotomy closures fail due to suture pull-through. We hypothesize that a novel suturable mesh device may limit pull-through via mechanisms of force distribution at the suture-tissue interface and fibrous encapsulation of the device filaments. This new tissue approximation device may lead to improved outcomes for laparotomy closure. Material and Methods Fifteen domestic swine 74 kg in size were randomly allocated to three groups for epigastric laparotomy closure with either size 0 suturable mesh, number 1 suturable mesh, or number 1 polypropylene. All three devices were placed in running fashion with 1 cm bites and 1 cm travels. Primary endpoints were hernia formation at 13 weeks and a semiquantitative analysis of the histological tissue response. Secondary endpoints included adhesions, surgical site occurrence (SSO), and documentation of “loose sutures”. Results There were numerically fewer hernias in the number 1 suturable mesh group. Nine of the 10 suturable mesh devices were well encapsulated within the tissues and could not be pulled away, while 4 of the 5 polypropylene sutures were loose. Adhesions were least for number 1 suturable mesh. Histologically, the suturable mesh implanted devices showed good fibrovascular ingrowth and were judged to be “non-irritants”. The soft tissue response was statistically greater (p = .006) for the number 1 suturable mesh than for the number 1 polypropylene. Conclusions The mechanism of how meshes support closure sites is clearly demonstrated with this model. Suturable mesh has the potential to change surgical algorithms for abdominal wall closure.

Carbon Nanomaterials Modified Biomimetic Dental Implants for Diabetic Patients.

Dental implants are used broadly in dental clinics as the most natural-looking restoration option for replacing missing or highly diseased teeth. However, dental implant failure is a crucial issue for diabetic patients in need of dentition restoration, particularly when a lack of osseointegration and immunoregulatory incompetency occur during the healing phase, resulting in infection and fibrous encapsulation. Bio-inspired or biomimetic materials, which can mimic the characteristics of natural elements, are being investigated for use in the implant industry. This review discusses different biomimetic dental implants in terms of structural changes that enable antibacterial properties, drug delivery, immunomodulation, and osseointegration. We subsequently summarize the modification of dental implants for diabetes patients utilizing carbon nanomaterials, which have been recently found to improve the characteristics of biomimetic dental implants, including through antibacterial and anti-inflammatory capabilities, and by offering drug delivery properties that are essential for the success of dental implants.

Reduction in Foreign Body Response and Improved Antimicrobial Efficacy via Silicone-Oil-Infused Nitric-Oxide-Releasing Medical-Grade Cannulas.

Foreign body response and infection are two universal complications that occur with indwelling medical devices. In response, researchers have developed different antimicrobial and antifouling surface strategies to minimize bacterial colonization and fibrous encapsulation. In this study, the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) and silicone oil were impregnated into silicone rubber cannulas (SR-SNAP-Si) using a solvent swelling method to improve the antimicrobial properties and decrease the foreign body response. The fabricated SR-SNAP-Si cannulas demonstrated a stable, prolonged NO release, exhibited minimal SNAP leaching, and maintained sliding angles < 15° for 21 days. SR-SNAP-Si cannulas displayed enhanced antimicrobial efficacy against Staphylococcus aureus in a 7-day biofilm bioreactor study, reducing the viability of adhered bacteria by 99.2 ± 0.2% compared to unmodified cannulas while remaining noncytotoxic toward human fibroblast cells. Finally, SR-SNAP-Si cannulas were evaluated for the first time in a 14- and 21-day subcutaneous mouse model, showing significantly enhanced biocompatibility compared to control cannulas by reducing the thickness of fibrous encapsulation by 60.9 ± 6.1 and a 60.8 ± 10.5% reduction in cell density around the implant site after 3 weeks. Thus, this work demonstrates that antifouling, NO-releasing surfaces can improve the lifetime and safety of indwelling medical devices.

Computational Modeling of an Endovascular Peripheral Nerve Interface.

Implantable neuromodulation devices that interface with the peripheral nervous system are a promising approach to restore functions lost to nerve damage. Existing nerve stimulation electrodes require direct contact with the target nerve and are associated with mechanical nerve damage and fibrous tissue encapsulation. Endovascularly delivered electrode arrays may provide a less invasive solution. Using a hybrid tissue conductor-neuron model and computational simulations, this study demonstrates the feasibility of delivering electrical stimulation of a peripheral nerve from a blood vessel in the vicinity of the target and predicts that the stimulation intensity required strongly depends on nerve-vessel distance and relative orientation, which are important factors to consider when screening candidate blood vessels for electrode implantation.

Suturable Mesh Demonstrates Improved Outcomes over Standard Suture in a Porcine Laparotomy Closure Model.

Background:Laparotomy closures fail due to suture pull-through. I hypothesize that a suturable mesh may limit pull-through via mechanisms of force distribution and fibrous encapsulation of the device filaments.Methods:Fifteen domestic swine 74 kg in size were randomly allocated to three groups for laparotomy closure with either size 0 suturable mesh, number 1 suturable mesh, or number 1 polypropylene. All three devices were placed in running fashion with 1-cm bites and 1-cm travels. Primary endpoints were hernia formation at 13 weeks and a semiquantitative analysis of the histological tissue response. Secondary endpoints included adhesions, surgical site occurrence (SSO), and documentation of “loose sutures.”Results:There were numerically fewer hernias in the number 1 suturable mesh group. Nine of the 10 suturable mesh devices were well encapsulated within the tissues and could not be pulled away, whereas four of the five polypropylene sutures were loose. Adhesions were least for number 1 suturable mesh. Histologically, the suturable mesh implanted devices showed good fibrovascular ingrowth and were judged to be “nonirritants.” The soft-tissue response was statistically greater (P = 0.006) for the number 1 suturable mesh than for the number 1 polypropylene.Conclusions:The mechanism by which meshes support closure sites is clearly demonstrated with this model. Suturable mesh has the potential to change surgical algorithms for abdominal wall closure.

Polycrystalline diamond coating on 3D printed titanium scaffolds: Surface characterisation and foreign body response

Titanium-based implants are the leading material for orthopaedic surgery, due to their strength, versatility, fabrication via additive manufacturing and invoked biological response. However, the interface between the implant and the host tissue requires improvement to better integrate the implant material and mitigate foreign body response. The interface can be manipulated by changing the surface energy, chemistry, and topography of the Titanium-based implant. Recently, polycrystalline diamond (PCD) has emerged as an exciting coating material for 3D printed titanium scaffolds showing enhanced mammalian cell functions while inhibiting bacterial attachment in vitro. In this study, we performed in-depth characterisation of PCD coatings investigating the surface topography, thickness, surface energy, and compared its foreign body response in vivo with uncoated titanium scaffold. Coating PCD onto titanium scaffolds resulted in a similar microscale surface roughness (RMS(PCD-coated) = 24 μm; RMS(SLM-Ti) = 28 μm), increased nanoscale roughness (RMS(PCD-coated) = 35 nm; RMS(SLM-Ti) = 66 nm) and a considerable decrease in surface free energy (E(PCD-coated) = 4 mN m−1; E(SLM-Ti) = 16 mN m−1). These surface property changes were supported by X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy as corresponding to observed surface chemistry changes induced by the coating. The underlying mechanism of how the diamond coatings chemical and physical properties changes the wettability of implants was examined. In vivo, the coated scaffolds induced similar level of fibrous encapsulation with uncoated scaffolds. This study thus provides further insight into the physicochemical characteristics of PCD coatings, adding evidence to the promising potential of PCD-coatings of medical implants.

The Foreign Body Response to an Implantable Therapeutic Reservoir in a Diabetic Rodent Model.

Advancements in type 1 diabetes mellitus treatments have vastly improved in recent years. The move toward a bioartificial pancreas and other fully implantable systems could help restore patient's glycemic control. However, the long-term success of implantable medical devices is often hindered by the foreign body response. Fibrous encapsulation "walls off" the implant to the surrounding tissue, impairing its functionality. In this study we aim to examine how streptozotocin-induced diabetes affects fibrous capsule formation and composition surrounding implantable drug delivery devices following subcutaneous implantation in a rodent model. After 2 weeks of implantation, the fibrous capsule surrounding the devices were examined by means of Raman spectroscopy, micro-computed tomography (μCT), and histological analysis. Results revealed no change in mean fibrotic capsule thickness between diabetic and healthy animals as measured by μCT. Macrophage numbers (CCR7 and CD163 positive) remained similar across all groups. True component analysis also showed no quantitative difference in the alpha-smooth muscle actin and extracellular matrix proteins. Although principal component analysis revealed significant secondary structural difference in collagen I in the diabetic group, no evidence indicates an influence on fibrous capsule composition surrounding the device. This study confirms that diabetes did not have an effect on the fibrous capsule thickness or composition surrounding our implantable drug delivery device. Impact Statement Understanding the impact diabetes has on the foreign body response (FBR) to our implanted material is essential for developing an effective drug delivery device. We used several approaches (Raman spectroscopy and micro-computed tomography imaging) to demonstrate a well-rounded understanding of the diabetic impact on the FBR to our devices, which is imperative for its clinical translation.

MP52-08 MACROPHAGE THERAPY VIA COLLAGEN BIOTEXTILE FOR THE TREATMENT OF STRESS URINARY INCONTINENCE

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II (MP52)1 Sep 2021MP52-08 MACROPHAGE THERAPY VIA COLLAGEN BIOTEXTILE FOR THE TREATMENT OF STRESS URINARY INCONTINENCE Ilaha Isali, Snigdha Cingireddi, Phillip McClellan, Mukesh Jain, James Anderson, Ozan Akkus, and Adonis Hijaz Ilaha IsaliIlaha Isali More articles by this author , Snigdha CingireddiSnigdha Cingireddi More articles by this author , Phillip McClellanPhillip McClellan More articles by this author , Mukesh JainMukesh Jain More articles by this author , James AndersonJames Anderson More articles by this author , Ozan AkkusOzan Akkus More articles by this author , and Adonis HijazAdonis Hijaz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002082.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recent reviews1,2 proposed the use of macrophages (MΦ) for regenerative purposes either by way of modifying biomaterials to attract host macrophages, or by direct delivery of MΦ. We have demonstrated the polarization of M0 macrophages to the pro-regenerative subtype-M2 upon seeding on genipin crosslinked collagen scaffold (GES). Current study aimed assess the long-term tissue response and post-surgical mechanical properties of implanted GES seeded with M0, M1, and M2 in a rat model. METHODS: Monocytes were harvested from rat bone-marrow. M0, M1 or M2 macrophages were polarized from monocytes and MΦ subtypes were confirmed by flow cytometry. Electrochemically aligned collagen threads were filament wound to produce small collagen scaffold genipin crosslinked. M0, M1 or M2 macrophages were seeded on GES and implanted subcutaneously in rats to determine whether MΦ supplementation improves the stiffness (i.e modulus) of regenerated tissue, collagen deposition by host, and alters the biology of healing. Implants were recovered at 3 months following which they were tested in tension, cellularity was quantified in H&E-stained sections, collagen production was quantified by automated image analysis of Masson’s trichrome sections, and fibrous capsule thickness was measured. RESULTS: M2-subtype seeded scaffolds (GES+M2) had the greatest modulus such that its magnitude was about 2.5 times greater than that of cell-free scaffolds (GES) whereas modulus of GES+M0 or GES+M1 did not differ significantly from that of cell-free scaffolds. Number of cells counts per unit area was the greatest for GES+M2 group, suggesting a greater degree of host cell attraction. Furthermore, alpha smooth muscle actin, a marker of myofibroblasts, was more notably present in M2-seeded scaffolds. M2 delivery induced greater amount of collagen deposition while limiting fibrous encapsulation of the scaffold. Net effect of M2-delivery was such that improved healing biomechanics that converged closer to the 3-5 MPa native tissue modulus range that the scaffold alone is unable to converge. CONCLUSIONS: In vivo delivery of M2-subtype by filament wound collagen scaffolds results in superior healing biomechanics and implant remodelling in comparison to other macrophage subtypes. Source of Funding: This work is supported by NIH grant: R21HD095439-01

Immunomodulatory Biomaterials for Tissue Repair.

All implanted biomaterials are targets of the host's immune system. While the host inflammatory response was once considered a detrimental force to be blunted or avoided, in recent years, it has become a powerful force to be leveraged to augment biomaterial-tissue integration and tissue repair. In this review, we will discuss the major immune cells that mediate the inflammatory response to biomaterials, with a focus on how biomaterials can be designed to modulate immune cell behavior to promote biomaterial-tissue integration. In particular, the intentional activation of monocytes and macrophages with controlled timing, and modulation of their interactions with other cell types involved in wound healing, have emerged as key strategies to improve biomaterial efficacy. To this end, careful design of biomaterial structure and controlled release of immunomodulators can be employed to manipulate macrophage phenotype for the maximization of the wound healing response with enhanced tissue integration and repair, as opposed to a typical foreign body response characterized by fibrous encapsulation and implant isolation. We discuss current challenges in the clinical translation of immunomodulatory biomaterials, such as limitations in the use of in vitro studies and animal models to model the human immune response. Finally, we describe future directions and opportunities for understanding and controlling the biomaterial-immune system interface, including the application of new imaging tools, new animal models, the discovery of new cellular targets, and novel techniques for in situ immune cell reprogramming.

The use of solvent-preserved human and bovine cancellous bone blocks for lateral defect augmentation - an experimental controlled study in vivo

BackgroundThe aim of this study was to compare new bone formation, resorbed bone matrix, and fibrous enclosed residual bone substitute material in laterally augmented alveolar bone defects using allogeneic, pre-treated and cleaned human bone blocks (tested in dogs, therefore considered to be xenogeneic), and pre-treated and cleaned bovine cancellous bone blocks, both with and without a collagen membrane in order to evaluate their augmentative potential.MethodsThirty-two critical size horizontal defects were prepared in the mandible of 4 adult foxhound dogs (8 per dog, 4 on each side). After 3 months of healing, the defects were laterally augmented in a split-mouth-design with either human (HXB) or bovine solvent-preserved bone blocks (BXB). Afterwards, defects were randomly covered with a bovine collagenous membrane (HXB + M, BXB + M). After a healing interval of 6 months, percentages of new bone formation, resorbed bone matrix, and fibrous enclosed residual bone substitute material were compared.ResultsResults showed little new bone formation of up to 3.7 % in human bone blocks (HXB 3.7 % ± 10.2, HXB + M 0.3 %± 0.4, BXB, 0.1 % ± 0.8, BXB + M 2.6 % ± 3.2, p = > 0.05). Percentages of fibrous encapsulation were higher in human bone blocks than in bovine bone blocks (HXB 71.2 % ± 8.6, HXB + M 73.71 % ± 10.6, BXB, 60.5 % ± 27.4, BXB + M 52.5 % ± 28.4, p = > 0.05). Resorption rates differed from 44.8 % in bovine bone blocks covered with a membrane to 17.4 % in human bone blocks (HXB 17.4 % ± 7.4, HXB + M 25.9 % ± 10.7, BXB, 38.4 % ± 27.2, BXB + M 44.8 % ± 29.6, p = > 0.05). The use of additional membranes did not significantly affect results.ConclusionsWithin its limitations, results of this study suggest that solvent-preserved xenogenic human and bovine bone blocks are not suitable for lateral bone augmentation in dogs. Furthermore, defect coverage with a membrane does not positively affect the outcome.

Cocoon abdomen: bowels in a web

Cocoon abdomen is a rare, idiopathic condition characterised by fibrous encapsulation of the bowel segments giving an appearance of a cocoon. The patient may present with variable and non-specific symptoms like abdominal pain, tenderness, vomiting and it sometimes even leads to intestinal obstruction. We hereby report a case of 54-year-old male who presented with symptoms of intestinal obstruction. Apart from the sparing of 60 mm of the resection margin at either ends, most of the segment was encased by the peritoneum giving a ‘spider-web’ appearance. On opening the intestinal segment, there were multiple areas of kinking of the wall with narrowing of the lumen in the areas of the ‘cocooning’. No obvious mass lesion was identified either on the mucosal aspect or in the mesentery. Microscopic examination revealed that multiple loops of small bowel were tethered together by a loose, oedematous fibrovascular membrane. Sclerosing encapsulating peritonitis (SEP) is an extremely rare clinical entity and was first described by Foo et al. in 1978,1 in an adolescent girl, which is reported to be the most common age group. Our case was found in a middle-aged male, which differs in both age group and sex of the common incidence of this entity. The aetiology of this condition remains unknown; however there have been cases where the patients have had a prior abdominal surgery, abdominal tuberculosis, liver transplant or recurrent peritonitis.2 1.Foo KT, Ng KC, Rauff A, et al. Unusual small intestinal obstruction in adolescent girls: The abdominal cocoon. Br J Surg 1978; 65: 427–30.2.Stanley MM, Reyes CV, Greenlee HB, et al. Peritoneal fibrosis in cirrhotics treated with peritoneovenous shunting for ascites. Digest Dis Sci 1996; 41: 571–7.

A Study on the Pathological Effects of Trypanorhyncha Cestodes in Dusky Groupers Epinephelus marginatus from the Canary Islands.

Simple SummaryTrypanorhyncha are common parasites of marine fish. Despite numerous studies detailing their biology, knowledge on the effects caused by these parasites in fish tissues is still limited. Dusky groupers are keystone species, necessary for the preservation of several marine ecosystems. Considering their vulnerable state of conservation and the efforts being made to culture them, identification of the effects caused by Trypanorhyncha is vital. Here, we have assessed the prevalence of Trypanorhyncha in dusky groupers from the Canary Islands and the associated pathological changes. Of the 28 fish examined, 27 presented trypanorhynch larvae. Macroscopically, in the abdominal cavity, there were numerous larvae-filled cysts and nodules embedded in abundant fibrosis, hindering the separation of the organs. Microscopically, in the peritoneum, stomach and intestine, there were numerous degenerated parasitic cysts and extensive deposition of fibrous connective tissue with minimal inflammatory responses. This study shows that Trypanorhyncha are common parasites of adult dusky groupers from the Canary Islands. Even though the immune system appears to isolate and eliminate the parasites, extensive fibrosis may have a detrimental impact on fish health when adjacent organs are compressed and their functions impaired.Trypanorhyncha are cestodes commonly infecting marine fish. Numerous studies have detailed the biology of Trypanorhyncha species, but information on the pathological changes produced by these parasites is limited. Dusky groupers are keystone species necessary for the preservation of several marine ecosystems. Considering their vulnerable state of conservation and the efforts being made to culture them, identification of the effects caused by Trypanorhyncha is vital. Here, we aimed to determine the prevalence and pathological changes produced by Trypanorhyncha in dusky groupers from the Canary Islands. The prevalence of trypanorhynch plerocerci was 96%. Grossly, in the abdominal cavity, there were numerous larvae-filled cysts and nodules. These were embedded in abundant fibrosis, producing visceral adhesions. Histologically, affecting the peritoneum, stomach, and intestine there were numerous degenerated encysted plerocerci and extensive deposition of mature connective tissue. These findings indicate that Trypanorhyncha is highly prevalent in adult dusky groupers from the Canary Islands, producing a progressive and chronic response. Furthermore, fish immune system appears to attempt to eliminate the parasites through fibrous encapsulation. Nonetheless, extensive fibrosis may have a detrimental impact on fish health when adjacent cells or tissues are compressed and their functions impaired.