Foreign Body Reaction Research Articles

A Histological Assessment Tool for Breast Implant Capsules Validated in 480 Patients with and Without Capsular Contracture

Abstract Background Understanding the impact of breast implants on the histological response in the surrounding fibrous capsule is important; however, consensus is lacking on how to analyze implant capsules histologically. We aimed to develop a standardized histological assessment tool to be used in research potentially improving diagnostic accuracy and treatment strategies for capsular contracture. Methods Biopsies of breast implant capsules from 480 patients who had undergone breast augmentation or reconstruction were collected and stained with hematoxylin and eosin. Initially, biopsies from 100 patients were analyzed to select histological parameters demonstrating the highest relevance and reproducibility. Then, biopsies from the remaining 380 patients were used to determine intra- and interobserver agreements of two blinded observers and agreement with a pathologist. Finally, we tested the association between the parameters and capsular contracture. Results The histological assessment tool included ten parameters assessing the inflammatory, fibrotic, and foreign-body reaction to breast implants, each graded on two-, three-, or four-point scales. Intra- and interobserver agreements were almost perfect (0.83 and 0.80), and agreement with the pathologist was substantial (0.67). Four parameters were significantly correlated with capsular contracture, namely chronic inflammation with lymphocyte infiltration (p < 0.01), thickness of the collagen layer (p < 0.0001), fiber organization (p < 0.01), and calcification (p < 0.001). Conclusions This is the first validated histological assessment tool for breast implant capsules. The validated tool not only advances our understanding of capsular contracture but also sets a new standard for histological evaluation in breast implant research and clinical diagnostics. No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Few incidentally found interesting foreign objects in human body: a case series

Foreign bodies are objects that do not typically belong in the human body but can be ingested, inserted, or entered due to injuries. This article presents various cases and examples of foreign bodies, including objects swallowed, objects inserted into the rectum, vagina, urethra, ear, and nose, or due to injuries caused by falls, puncture wounds, and gunshot wounds. Foreign bodies can be difficult to detect, particularly if they are not inherently radio-opaque, and may be overlooked by patients who cannot provide an adequate history. These foreign bodies may cause harm to the patient. Interpretation is done on radiographs, computed tomography (CT), Ultrasonography (USG), and magnetic resonance imaging (MRI) studies. Most foreign objects pass through the gastrointestinal tract without problem; sharp and elongated objects can cause significant injury, and even if they only partially perforate the bowel wall, they can produce chronic inflammatory processes that produce symptoms months or years later. Hence, searching for foreign bodies should be done throughout the gastrointestinal tract, particularly in children and people with mental illness who are more likely to swallow multiple items more than once. Although rare, various materials can be left behind in the body of a patient after surgery, including large and small wire sutures, surgical drains, and retained sponges, which can cause potential complications and foreign body reactions. This article highlights the importance of being aware of the presence of foreign bodies in clinical practice, and a thorough search should be carried out using different modalities, especially CT. Great suspicion and early diagnosis of foreign bodies can avoid potential complications and morbidity. In general, it provides information on the diagnosis and treatment of various types of foreign bodies.

Biomechanical and Histological Study of Retrieved LARS Synthetic Ligaments

Background: Synthetic grafts have been used for a number of years in anterior cruciate ligament (ACL) reconstruction surgery. One of the more recent additions to the stable of synthetic ligaments is the Ligament Augmentation and Reconstruction System (LARS) ligament. Purpose: To analyze the biomechanics and histology of LARS grafts retrieved due to failure of the device. Study Design: Descriptive laboratory study. Methods: A total of 22 LARS ligament grafts that were explanted from patients were sent for analysis. Five new, unused samples of the standard LARS ACL graft were also analyzed. Biomechanical testing was performed: ultimate tensile force, force versus displacement, and stress versus strain were recorded. Histopathological examination was performed looking for degree of fibrous tissue ingrowth as well as the presence of a foreign body reaction. Results: Of the 22 grafts retrieved, 14 were used for ACL grafts, 1 for a lateral collateral ligament graft, 2 for medial collateral ligament grafts, 4 for gluteal tendon augmentation, and 1 for a supraspinatus augmentation. A severe foreign body reaction was found in 86% of the grafts (18/22) and a mild foreign body reaction in the remaining 14% (4/22). Tissue ingrowth was minimal in the majority of ACL grafts; the other grafts showed moderate tissue ingrowth. Maximal tensile force was significantly higher for the new ACL grafts (mean ± SD, 1667 ± 845 N) compared with the retrieved grafts (897 ± 395 N; P < .05). Conclusion: This study demonstrated that the vast majority of retrieved LARS artificial ligaments had a florid foreign body reaction. There was minimal tissue ingrowth in ACL grafts and moderate ingrowth in other grafts. Retrieved grafts had a decreased ultimate tensile force, which increased their risk of rupture. Clinical Relevance: Surgeons should be cautious in choosing to use these grafts in reconstructive surgery for patients.

Instantly adhesive and ultra-elastic patches for dynamic organ and wound repair

Bioadhesive materials and patches are promising alternatives to surgical sutures and staples. However, many existing bioadhesives do not meet the functional requirements of current surgical procedures and interventions. Here, we present a translational patch material that exhibits instant adhesion to tissues (2.5-fold stronger than Tisseel, an FDA-approved fibrin glue), ultra-stretchability (stretching to >300% its original length without losing elasticity), compatibility with rapid photo-projection (<2 min fabrication time/patch), and ability to deliver therapeutics. Using our established procedures for the in silico design and optimization of anisotropic-auxetic patches, we created next-generation patches for instant attachment to tissues while conforming to a broad range of organ mechanics ex vivo and in vivo. Patches coated with extracellular vesicles derived from mesenchymal stem cells demonstrate robust wound healing capability in vivo without inducing a foreign body response and without the need for patch removal that can cause pain and bleeding. We further demonstrate a single material-based, void-filling auxetic patch designed for the treatment of lung puncture wounds.

Neuronal functional connectivity is impaired in a layer dependent manner near chronically implanted intracortical microelectrodes in C57BL6 wildtype mice

Objective. This study aims to reveal longitudinal changes in functional network connectivity within and across different brain structures near chronically implanted microelectrodes. While it is well established that the foreign-body response (FBR) contributes to the gradual decline of the signals recorded from brain implants over time, how the FBR affects the functional stability of neural circuits near implanted brain–computer interfaces (BCIs) remains unknown. This research aims to illuminate how the chronic FBR can alter local neural circuit function and the implications for BCI decoders. Approach. This study utilized single-shank, 16-channel,100 µm site-spacing Michigan-style microelectrodes (3 mm length, 703 µm2 site area) that span all cortical layers and the hippocampal CA1 region. Sex balanced C57BL6 wildtype mice (11–13 weeks old) received perpendicularly implanted microelectrode in left primary visual cortex. Electrophysiological recordings were performed during both spontaneous activity and visual sensory stimulation. Alterations in neuronal activity near the microelectrode were tested assessing cross-frequency synchronization of local field potential (LFP) and spike entrainment to LFP oscillatory activity throughout 16 weeks after microelectrode implantation. Main results. The study found that cortical layer 4, the input-receiving layer, maintained activity over the implantation time. However, layers 2/3 rapidly experienced severe impairment, leading to a loss of proper intralaminar connectivity in the downstream output layers 5/6. Furthermore, the impairment of interlaminar connectivity near the microelectrode was unidirectional, showing decreased connectivity from Layers 2/3 to Layers 5/6 but not the reverse direction. In the hippocampus, CA1 neurons gradually became unable to properly entrain to the surrounding LFP oscillations. Significance. This study provides a detailed characterization of network connectivity dysfunction over long-term microelectrode implantation periods. This new knowledge could contribute to the development of targeted therapeutic strategies aimed at improving the health of the tissue surrounding brain implants and potentially inform engineering of adaptive decoders as the FBR progresses. Our study’s understanding of the dynamic changes in the functional network over time opens the door to developing interventions for improving the long-term stability and performance of intracortical microelectrodes.

In vivo comparison of customized zirconia barriers in guided bone regeneration: An experimental study

ObjectiveThis study aims to evaluate the effects of customized zirconia barrier membranes produced for guided bone regeneration (GBR) approaches on bone healing researched with histological and histomorphometric methods. MethodsThe digital modeling was used to create zirconia barrier membranes suitable for the defect on the tibia bone. The membranes were designed using a 3D software system and transferred to the CAD/CAM software system in stl. Afterward, zirconia discs (1400 Mpa) (Aconia BSM- D98 × 16, HT+, Germany) were milled and sintered. Titanium mesh, titanium reinforced d-PTFE, and zirconia barrier membranes were used to cover the defects. As a control group, one defect was left empty. 3 and 6 weeks of the healing term, preparates were obtained from each group after animals were sacrificed. New bone formation, amount of the remaining grafts and tissue response parameters were analyzed histomorphometrically and histologically. ResultsThe highest percentage of newly formed bone in the early period was observed in the titanium mesh membrane group (26.39 ± 5.38); In the late period, this rate was highest in the zirconia group (64.42 ± 9.95). However, no statistically significant difference was found in both periods between the groups. The amount of residual graft progressed at a low level in both periods without any difference in the other groups except the control group. In the 3rd and 6th weeks, the amount of new bone formation was the lowest in the control group. No foreign body reaction or necrosis was observed in any of the defects. ConclusionWith the limitation of the study, it has been concluded that effective results can be obtained with customized zirconia barrier membranes in GBR procedures.

Oxidised cellulose-based reaction mimicking a suspicious ovarian mass: a case report and a systematic review.

Oxidised regenerated cellulose was introduced 60 years ago to control diffuse bleeding from large surfaces. Although considered safe and effective, foreign body reactions can mimic suspicious masses in several organs. We describe the third case, reported in PubMed, of an oxidised regenerated cellulose-based granuloma mimicking a suspicious ovarian tumour on MRI. During surgery, the diagnosis was suspected by granulomatous tissue and confirmed by pathology. The follow-up after the excision was uneventful. Although a rare complication, physicians should be aware of this presentation and of the recommendation to remove excess Surgicel after the bleeding has stopped.

Design of Three-Dimensional-Printed Compression Ring for Enhanced Wound Healing of Colorectal Anastomosis to Minimize Dehiscence and Leakage Post Colectomy

Abstract Bowel resection surgery, also known as colectomy, is a primary therapeutic intervention where a neoplastic or cancerous segment of the bowel is removed and an anastomosis constructed to reestablish intestinal continuity. Several techniques can be used to create the anastomosis, including mechanical staplers or manual sutures. A potentially life-threatening complication in colon anastomosis is dehiscence and leakage. Various contributing factors can hinder the formation of anastomosis, including technical failure (human error, staple malfunction), inflammation caused by foreign body response (sutures and staples), collagenolytic bacteria, and patient comorbidities (chemotherapy, old age, and obesity). Here, we report a three-dimensional (3D)-printed compression ring with electrical stimulation (ES) functionality to improve wound healing and anastomotic closure. The device consists of a one-way locking mechanism for initial deployment, an elastic band tightening mechanism to secure seal as tissue heals, and electrodes for electrical stimulation to enhance wound healing. The compression ring was assembled with 83.4±3.9 N of force and delivers 147.5±8.8 kPa of pressure to tissue, effectively restricting blood flow to the clamped tissue. This helps to create the anastomosis between remaining tissue on either side. Our design facilitates manual assembly without necessitating an additional delivery device. Electrical impedance analysis confirmed adequate tissue–electrode contact. We tested this device with ex vivo ovine intestinal tissue and confirmed that the compression ring was able to withstand up to 2.0±0.4 kPa intraluminal pressure immediately following installation. By combining mechanical strength and electrical stimulation, this device could potentially improve wound healing, anastomotic closure, and minimize the risk of leaks.

Histological Evaluation of Alveolar Ridge Preservation Using Different Bone Grafts: Clinical Study Analysis Part II.

To compare histologically the percentage of bone formation 12-20 weeks after ridge augmentation using 2 different techniques. Tooth loss is associated with 3-dimensional bone remodeling and ridge atrophy. Ridge preservation procedures can prevent alveolar bone volume loss. Different techniques and materials are used to preserve the alveolar ridge. Computer-generated randomization software was used to assign 2 ridge preservation techniques for 11 extraction sites. In group I, type I bovine Achilles tendon collagen plugs with bioactive resorbable calcium apatite crystals (CPCAC) were placed, and in group II, cortico-cancellous bone chips (CCBC) mix and an expanded polytetrafluoroethylene (ePTFE) barrier membrane were placed. The histomorphometric studies were performed using a computer-based image analysis system (ImageJ 1.4, National Institute of Health, Bethesda, Md) to calculate the pixel area of bone tissue and the remaining bone graft material. The histomorphometric data were analyzed using a Student t test to compare the measurements between the 2 experimental groups. This parametric statistical test was employed to determine if there were any statistically significant differences in the quantitative histological parameters between the groups. The sockets that received CPCAC showed a lower (31.89%) percentage of native bone surface area compared with the CCBC group (43.87%). However, the difference was not statistically significant (P < .05). In addition, the CPCAC group showed evidence of foreign-body reaction. The CCBC graft covered with an ePTFE barrier may induce more bone formation with minimal inflammation in an extraction socket compared with a collagen plug with calcium apatite crystals. In addition, histological analysis of the CPCAC graft showed evidence of foreign-body reaction, which indicates a negative clinical impact.

Long-Term Evaluation of Inserted Nanocomposite Hydrogel-Based Phosphorescent Oxygen Biosensors: Evolution of Local Tissue Oxygen Levels and Foreign Body Response.

Phosphorescence-based oxygen-sensing hydrogels are a promising platform technology for an upcoming generation of insertable biosensors that are smaller, softer, and potentially more biocompatible than earlier designs. However, much remains unknown about their long-term performance and biocompatibility in vivo. In this paper, we design and evaluate a range of hydrogel sensors that contain oxygen-sensitive phosphors stabilized by micro- and nanocarrier systems. These devices demonstrated consistently good performance and biocompatibility in young adult rats for over three months. This study thoroughly establishes the biocompatibility and long-term suitability of phosphorescence lifetime sensors in vivo, providing the groundwork for expansion of this platform technology into a family of small, unobtrusive biosensors for a range of clinically relevant metabolites.

Coatings for Permanent Meshes Used to Enhance Healing in Abdominal Hernia Repair: A Scoping Review.

Hernia meshes are used to reduce recurrence and pain rates, but the rates are still high. This could be improved with coatings of the mesh. This scoping review aimed to provide an overview of mesh coatings used to promote healing in abdominal hernia repair and to report beneficial and unbeneficial effects. We included human and animal studies with abdominal hernias that were repaired with non-commercially coated meshes. We searched Pubmed, Embase, Cochrane Central, LILACS, and CNKI without language constraints. Of 2933 identified studies, 58 were included: six studies had a total of 408 humans and 52 studies had 2679 animals. The median follow-up was 12 months (range 1-156), and 95% of the hernias were incisional. There were 44 different coatings which included platelet-rich plasma, mesenchymal stem cells, growth factors, vitamin E, collagen-derived products, various polysaccharides, silk proteins, chitosan, gentamycin, doxycycline, nitrofurantoin, titanium, and diamond-like carbon. Mesenchymal stem cells and platelet-rich plasma were the most researched. Mesenchymal stem cells notably reduced inflammation and foreign body reactions but did not impact other healing metrics. In contrast, platelet-rich plasma positively influenced tissue ingrowth, collagen deposition, and neovascularization and had varying effects on inflammation and foreign body reactions. We identified 44 different mesh coatings and they showed varying results. Mesenchymal stem cells and platelet-rich plasma were the most studied, with the latter showing considerable promise in improving biomechanical properties in hernia repair. Further investigations are needed to ascertain their definitive use in humans.

HERNIA MESH EXPLANTATION FOR MESH INGUINODYNIA AND ALLODYNIA. WHY IS HERNIA MESH SO PAINFUL?

Abstract Introduction Chronic pain after mesh repair for abdominal wall hernia is an indication for the removal of mesh and reconstruction by a non-mesh technique. Materials and Methods In a consecutive series over 19 years, 128 patients had mesh removed to relieve chronic pain. This open method of mesh removal relies on confirming normal anatomical landmarks. The superior and inferior leaf of the External oblique aponeurosis are raised, the spermatic cord is identified and retracted. The mesh is gently dissected off the Internal oblique from lateral to medial, taking care in preserving the vas, and accompanying vessels. Adherent ilio-inguinal, iliohypogastric and genitofemoral nerves are removed with the mesh. The resultant recurrent hernia is repaired by Moloney darn, a tension-free tissue repair. Results 128 consecutive patients have been treated by mesh explantation and immediate reconstruction on average 6 years after implantation. Resolution of symptoms was experienced very shortly after the mesh removed. Preperitoneal mesh particularly Kugel patch has been the most difficult to remove. Meshes have been submitted for histological examination and the findings are usually chronic granulomatous foreign body reaction. Few complications have been encountered with a follow-up period ranging from 6 months to 15 years, the most common being the failure of explantation to alleviate inguinal pain in the long-term. Conclusion All hernia patients should be afforded informed consent including discussing the potential long-term consequences of chronic groin and abdominal pain.

Tannic acid and quaternized chitosan mediated puerarin-loaded octacalcium phosphate /sodium alginate scaffold for bone tissue engineering

Current limitations in mechanical performance and foreign body reactions (FBR) often lead to implant failure, restricting the application of bioceramic scaffolds. This study presents a novel 3D-printed scaffold that combines the release of anti-inflammatory drugs with osteogenic stimulation. Initially, the inorganic and organic phases were integrated to ensure the scaffold's mechanical integrity through catechol chemistry and the electrostatic interactions between tannic acid and quaternary ammonium chitosan. Subsequently, layers of polydopamine-encapsulated puerarin-loaded zeolitic imidazolate framework-8 (ZIF-8) were self-assembled onto the stent's surface, creating the drug-loaded scaffold that improved drug release without altering the scaffold's structure. Compared with unloaded scaffolds, the puerarin-loaded scaffold demonstrated excellent osteogenic differentiation properties along with superior anti-inflammatory and osteogenic effects in a range of in vitro and in vivo studies. RNA sequencing clarified the role of the TNF and NF/κB signaling pathways in these effects, further supporting the scaffold's osteogenic potential. This study introduces a novel approach for creating drug-loaded scaffolds, providing a unique method for treating cancellous bone defects.

#1217 Reinsertion of peritoneal dialysis catheter in a patient with Nocardial peritonitis: a case report

Abstract Background and Aims Peritonitis is a major drawback in patients on PD leading to technique failure, change in modality to hemodialysis, mortality. Nocardia infections are rare and occur mainly in immunocompromised individuals. Eleven cases of Nocardial peritonitis only have been reported. Given the rarity of the condition, duration of medical treatment, time at which catheter reinsertion can be done after treatment are not clear. We describe a case of nocardial peritonitis which presented with tunnel abscess and septic shock. Method Our patient is a 65 yr/M, DM &amp; HT, initiated on CAPD due to multiple access failure elsewhere. He was also on treatment with directly acting antiviral for HCV infection. He presented with fever, abdominal pain and cloudy peritoneal fluid. Vitals were HR 98/min, BP 90/ 60 mmHg, temperature 100 F. Abdominal examination showed insertion and exit site pus with tenderness (Fig. 1a,b). USG screening showed tunnel abscess. Labs showed hemoglobin 7.2 g/dL, white blood cell count 6200 cells/cu mm, platelet count 1.4 lakh/cu mm, SGOT 23 U/L, SGPT 15 U/L and peritoneal dialysis fluid count 1570. CT abdomen showed no intraabdominal abscess. He was started on intravenous antibiotic and ionotropic support. Emergent PD catheter removal was done in view of septic shock &amp; was dialysed via femoral tunneled catheter. Pus and peritoneal fluid culture grew Nocardia spp after six days of incubation. Intravenous cotrimoxazole was given for 2 weeks and intravenous ceftriaxone was given for 4 weeks followed by oral cotrimoxazole 960 mg thrice weekly. Results Following 7 months of treatment with cotrimoxazole, PD catheter was inserted laparoscopically after omentectomy and adhesiolysis. Peritoneal biopsy was taken at the time of catheter insertion, histopathology showed fragments of peritoneal tissue with scattered chronic inflammatory cells, culture was negative for Nocardia. PD catheter outflow dysfunction was noted after initiation of exchanges. CT abdomen showed migration of PD catheter tip following which catheter tip repositioning was done laparoscopically. During procedure, nodules were noted over peritoneum and bowel. Biopsy of the nodules were revealed foreign body granuloma and culture did not grow Nocardia (Fig. 2). Patient was initiated on three exchanges with 2.5% dextrose per day after a break-in period of 14 days. He continues to be on PD with good ultrafiltration. Conclusion There is not much data on reinsertion of PD catheter after nocardial peritonitis. One case of Nocardial peritonitis reported in literature, in which PD catheter was reinserted. Jamie Kendrick-Jones et al. [1] reported a case of Nocardial peritonitis in which catheter was reinserted after 1 year. To our knowledge this is the first case of Nocardial peritonitis which presented with tunnel abscess. Catheter was removed due to septic shock. Patient was treated with cotrimoxazole for seven months after which PD catheter insertion was done. Return to PD is feasible if Nocardial infection is identified and treated appropriately.

Migrating foreign body granulomas after rupture of a breast implant

AbstractWe present the case of an 80‐year‐old female with a history of bluish streaks and painful lumps on her left arm, initially misdiagnosed as a soft tissue infection. Further investigation revealed granulomatous infiltrates in the arm and a ruptured breast implant. Upon presentation, nodular and painful swelling prompted a new biopsy. Histology and electron spectroscopy confirmed silicone deposits within granulomas. The rupture of the breast implant was identified as the likely source of silicone migration to the arm, possibly exacerbated by a past fall. Treatment challenges included the extensive size of the granuloma, leading to a trial of methotrexate therapy with initial improvement but subsequent discontinuation due to poor tolerance. This case underscores the potential for silicone migration from ruptured breast implants to induce distant granulomatous reactions, necessitating individualised treatment 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.

Ultrasonographic features of nonvascular complications of hyaluronic acid fillers: a retrospective study at a reference center for dermatologic ultrasonography

Hyaluronic acid filler injections have been associated with early, temporary, and delayed-onset complications. High-resolution ultrasound with Doppler analysis has been increasingly used to detect and identify such complications. We comprehensively describe the most common ultrasonographic findings of nonvascular complications associated with hyaluronic acid filler injections. This retrospective, cross-sectional, observational study was conducted at a reference center for dermatologic ultrasound in Bogotá, Colombia. Ultrasound reports documented the ultrasonographic findings of nonvascular complications of hyaluronic acid filler injections. Fifty-two complications were documented in a cohort of 50 patients (women, 88%). The infraorbital region was the most common site affected (23%), followed by the nasolabial region (22%). The Tyndall effect was the most common complication (25% of all), followed by changes in rheology (21%) and pseudosarcoidal (foreign body granuloma) reaction (15%). The Tyndall effect stood out for its distinctive ultrasonographic characteristics. We discuss the ultrasonographic findings and pathogenesis of other complications, including filler migration, early hypersensitivity, aseptic abscess, overcorrection, and filler material interaction. The clinical presentation of hyaluronic acid filler complications can be confusing, delaying timely diagnosis and treatment. High-resolution ultrasound with Doppler analysis is a valuable tool for avoiding unnecessary treatments and ensuring timely diagnosis and treatment.

A xenogeneic extracellular matrix-based 3D printing scaffold modified by ceria nanoparticles for craniomaxillofacial hard tissue regeneration via osteo-immunomodulation

Hard tissue engineering scaffolds especially 3D printed scaffolds were considered an excellent strategy for craniomaxillofacial hard tissue regeneration, involving crania and facial bones and teeth. Porcine treated dentin matrix (pTDM) as xenogeneic extracellular matrix has the potential to promote the stem cell differentiation and mineralization as it contains plenty of bioactive factors similar with human-derived dentin tissue. However, its application might be impeded by the foreign body response induced by the damage-associated molecular patterns of pTDM, which would cause strong inflammation and hinder the regeneration. Ceria nanoparticles (CNPs) show a great promise at protecting tissue from oxidative stress and influence the macrophages polarization. Using 3D-bioprinting technology, we fabricated a xenogeneic hard tissue scaffold based on pTDM xenogeneic TDM-polycaprolactone (xTDM/PCL) and we modified the scaffolds by CNPs (xTDM/PCL/CNPs). Through series of in vitro verification, we found xTDM/PCL/CNPs scaffolds held promise at up-regulating the expression of osteogenesis and odontogenesis related genes including collagen type 1, Runt-related transcription factor 2 (RUNX2), bone morphogenetic protein-2, osteoprotegerin, alkaline phosphatase (ALP) and DMP1 and inducing macrophages to polarize to M2 phenotype. Regeneration of bone tissues was further evaluated in rats by conducting the models of mandibular and skull bone defects. The in vivo evaluation showed that xTDM/PCL/CNPs scaffolds could promote the bone tissue regeneration by up-regulating the expression of osteogenic genes involving ALP, RUNX2 and bone sialoprotein 2 and macrophage polarization into M2. Regeneration of teeth evaluated on beagles demonstrated that xTDM/PCL/CNPs scaffolds expedited the calcification inside the scaffolds and helped form periodontal ligament-like tissues surrounding the scaffolds.

Mechanically robust and personalized silk fibroin-magnesium composite scaffolds with water-responsive shape-memory for irregular bone regeneration

The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.

Advanced age is not a barrier to chronic intracortical single-unit recording in rat cortex.

Available evidence suggests that as we age, our brain and immune system undergo changes that increase our susceptibility to injury, inflammation, and neurodegeneration. Since a significant portion of the potential patients treated with a microelectrode-based implant may be older, it is important to understand the recording performance of such devices in an aged population. We studied the chronic recording performance and the foreign body response (FBR) to a clinically used microelectrode array implanted in the cortex of 18-month-old Sprague Dawley rats. To the best of our knowledge, this is the first preclinical study of its type in the older mammalian brain. Here, we show that single-unit recording performance was initially robust then gradually declined over a 12-week period, similar to what has been previously reported using younger adult rats and in clinical trials. In addition, we show that FBR biomarker distribution was similar to what has been previously described for younger adult rats implanted with multi-shank recording arrays in the motor cortex. Using a quantitative immunohistochemcal approach, we observed that the extent of astrogliosis and tissue loss near the recording zone was inversely related to recording performance. A comparison of recording performance with a younger cohort supports the notion that aging, in and of itself, is not a limiting factor for the clinical use of penetrating microelectrode recording arrays for the treatment of certain CNS disorders.