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The direct modulation of T cell responses is an emerging therapeutic strategy with the potential to modulate undesired immune responses including, autoimmune disease, and allogeneic cells transplantation. We have previously demonstrated that poly(lactide-co-glycolide) particles were able to modulate T cell responses indirectly through antigen-presenting cells (APCs). In this report, we investigated the design of nanoparticles that can directly interact and modulate T cells by coating the membranes from APCs onto nanoparticles to form membrane-coated nanoparticles (MCNPs). Proteins within the membranes of the APCs, such as Major Histocompatibility Complex class II and co-stimulatory factors, were effectively transferred to the MCNP. Using alloreactive T cell models, MCNP derived from allogeneic dendritic cells were able to stimulate proliferation, which was not observed with membranes from syngeneic dendritic cells and influenced cytokine secretion. Furthermore, we investigated the engineering of the membranes either on the dendritic cells or postfabrication of MCNP. Engineered membranes could be to promote antigen-specific responses, to differentially activate T cells, or to directly induce apoptosis. Collectively, MCNPs represent a tunable platform that can directly interact with and modulate T cell responses., (© 2022 Wiley Periodicals LLC.)

Surgical-site infections (SSIs) occur in 2-5% of patients undergoing surgery in the US alone, impacting 300 000-500 000 lives each year, and presenting up to 11 times greater risk of death compared to patients without SSIs. The most common cause of SSI is Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) is the most common pathogen in community hospitals. Current clinical devices used for approximating incisions and traumatic lacerations include sutures, adhesives, tapes, or staples with or without antimicrobial incorporation. However, current closure technologies may not provide adequate protection against infection, are susceptible to wound dehiscence, and can result in delayed biomechanical recoveries. Laser-activated tissue repair is a sutureless technique in which chromophore-loaded sealants convert laser light energy to heat in order to induce rapid tissue sealing. Here, we describe the generation and evaluation of laser-activated sealant (LASE) biomaterials, in which, indocyanine green (ICG), an FDA-approved dye, was embedded in a silk fibroin matrix and cast into films as wound sealants. Silk-ICG films were subjected to different near-infrared (NIR) laser powers to identify temperatures optimal for laser sealing of soft tissues. A mathematical model was developed in order to determine the photothermal conversion efficiency of LASEs following laser irradiation. NIR laser activation of silk-ICG LASEs increased the recovery of skin biomechanical strength compared to sutured skin in full-thickness incisional wounds in immunocompetent mice, and live animal imaging indicated persistence of silk-ICG LASEs over several days. LASEs loaded with the antibiotic vancomycin demonstrated higher efficacies for combating MRSA infections in a mouse model of surgical site infection compared to antibacterial sutures. Our results demonstrate that LASEs can be loaded with antimicrobial drugs and may serve as new multifunctional biomaterials for rapid tissue sealing, repair and surgical site protection following surgery.

Sutures are typically the primary means of soft tissue repair in surgery and trauma. Despite their widespread use, sutures do not result in immediate sealing of approximated tissues, which can result in bacterial infection and leakage. Nonabsorbable sutures and staples can be traumatic to tissue, and the trauma can be exacerbated by their subsequent removal. Use of cyanoacrylate glues is limited because of their brittleness and toxicity. In this work, laser-activated tissue-integrating sutures (LATIS) are described as novel nanodevices for soft tissue approximation and repair. Incorporation of gold nanorods within fibers generated from collagen result in LATIS fibers which demonstrate robust photothermal responses following irradiation with near infrared laser light. Compared to conventional sutures, LATIS fibers result in greater biomechanical recovery of incised skin in a mouse model of skin closure after spine surgeries. Histopathology analyses show improved repair of the epidermal gap in skin, which indicate faster tissue recovery using LATIS. The studies indicate that LATIS-facilitated approximation of skin in live mice synergizes the benefits of conventional suturing and laser-activated tissue integration, resulting in new approaches for faster sealing, tissue repair, and healing., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Tissue approximation and repair have been conventionally performed with sutures and staples, but these means are inherently traumatic. Tissue approximation using laser-responsive nanomaterials can lead to rapid tissue sealing and repair, and is an attractive alternative to existing clinical methods. Here, we demonstrate the use of laser-activated nanosealants (LANS) with gold nanorods (GNRs) embedded in silk fibroin polypeptide matrices. The adaptability of LANS for sealing soft tissues is demonstrated using two different modalities: insoluble thin films for internal, intestinal tissue repair, and semi-soluble pastes for external repair, shown by skin repair in live mice. Laser repaired intestinal tissue held over seven times more fluid pressure than sutured intestine and also prevented bacterial leakage. Skin incisions in mice closed using LANS' showed indication of increased mechanical strength and faster repair compared to suturing. Laser-activated silk-GNR nanosealants rapidly seal soft-tissue tears and show high promise for tissue approximation and repair in trauma and routine surgery.

Inorganic nanomaterials have witnessed significant advances in areas of medicine including cancer therapy, imaging, and drug delivery, but their use in soft tissue repair and regeneration is in its infancy. Metallic, ceramic, and carbon allotrope nanoparticles have shown promise in facilitating tissue repair and regeneration. Inorganic nanomaterials have been employed to improve stem cell engraftment in cellular therapy, material mechanical stability in tissue repair, electrical conductivity in nerve and cardiac regeneration, adhesion strength in tissue approximation, and antibacterial capacity in wound dressings. These nanomaterials have also been used to improve or replace common surgical materials and restore functionality to damaged tissue. We provide a comprehensive overview of inorganic nanomaterials in tissue repair and regeneration, and discuss their promise and limitations for eventual translation to the clinic.

Objective: Laser tissue soldering using photothermal solders is a technology that facilitates rapid sealing using heat-induced changes in the tissue and the solder material. The solder material is made of gold nanorods embedded in a protein matrix patch that can be placed over the tissue rupture site and heated with a laser. Although laser tissue soldering is an attractive approach for surgical repair, potential photothermal damage can limit the success of this approach. Development of predictive mathematical models of photothermal effects including cell death, can lead to more efficient approaches in laser-based tissue repair., Methods: We describe an experimental and modeling investigation into photothermal solder patches for sealing porcine and mouse cadaver intestine sections using near-infrared laser irradiation. Spatiotemporal changes in temperature were determined at the surface as well as various depths below the patch. A mathematical model, based on the finite element method, predicts the spatiotemporal temperature distribution in the patch and surrounding tissue, as well as concomitant cell death in the tissue is described., Results: For both the porcine and mouse intestine systems, the model predicts temperatures that are quantitatively similar to the experimental measurements with the model predictions of temperature increase often being within a just a few degrees of experimental measurements., Conclusion: This mathematical model can be employed to identify optimal conditions for minimizing healthy cell death while still achieving a strong seal of the ruptured tissue using laser soldering. Lasers Surg. Med. 50:143-152, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Surgical site infection and postoperative leakage are complications that may develop following colorectal surgery and result in fatal consequences. Rapid, fluid-tight wound closure through laser tissue welding (LTW) can reduce postoperative leakage and thus decrease infection. Laser tissue welding involves generation of localized heat by exposing an exogenous chromophore to near-infrared (NIR) irradiation in order to seal wounds. In this study, we generated gold nanorod (GNR)-collagen nanocomposites (NCs) for laser-facilitated welding of ruptured intestinal tissue. The fluid content, stiffness, elasticity, and laser-induced temperature response of these nanocomposites were modulated to optimize laser-induced tissue fusion and minimize tissue damage. In addition, the effect of laser operating parameters including power density, femtosecond pulsed wave (PW) or continuous wave (CW) laser, and exposure duration were all studied. Laser power density and treatment duration significantly affected the temperatures reached during welding, as well as tissue weld strength and burst pressure. CW laser was found to induce significantly higher temperatures of the nanocomposites during treatment than PW laser, but the differences in weld strength and burst pressure for the two laser types were insignificant. This suggests that PW lasers can result in robust welds while minimizing potential thermal damage compared to CW lasers. The ultimate tensile strength of welded ruptured tissue was returned to as high as 68% of the native tissue strength through laser treatment, and laser treatment with these nanocomposites restored up to 64% of native tissue leak pressure and 42% of burst pressure. To the best of our knowledge, the laser power densities used (≤2.50 W/cm 2 ) are among the lowest reported for laser tissue welding, and the laser configuration and use require very little surgical skill. Our results indicate that GNR-collagen nanocomposites are promising photothermal biomaterials in laser tissue welding applications.