ABSTRACT
Local recurrence post-surgery in early-stage triple-negative breast cancer is a major challenge. To control the regrowth of a residual tumor, we have developed an autologous therapeutic hybrid fibrin glue for intra-operative implantation. Using autologous serum proteins as stabilizers, we have optimized high drug-loaded lapatinib-NanoSera (Lap-NS; â¼66% L.C.) and imiquimod-MicroSera (IMQ-MS; â¼92% L.C). Additionally, plasmonic nanosera (PNS) with an â¼67% photothermal conversion efficiency under 980 nm laser irradiation was also developed. While localized monotherapy with either Lap-NS or PNS reduced the tumor regrowth rate, their combination with IMQ-MS amplified the effect of immunogenic cell death with a high level of tumor infiltration by immune cells at the surgical site. The localized combination immunotherapy with a Nano-MicroSera based hybrid fibrin implant showed superior tumor inhibition and survival with significant promise for clinical translation.
Subject(s)
Imiquimod , Female , Animals , Humans , Mice , Cell Line, Tumor , Imiquimod/chemistry , Imiquimod/pharmacology , Lapatinib/chemistry , Lapatinib/pharmacology , Immunotherapy , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Neoplasm Recurrence, Local/prevention & control , Fibrin/chemistry , Triple Negative Breast Neoplasms/therapy , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/drug therapy , Fibrin Tissue Adhesive/chemistry , Fibrin Tissue Adhesive/pharmacology , Mice, Inbred BALB C , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic useABSTRACT
Accidental events or surgical procedures usually lead to tissue injury. Fibrin sealants have proven to optimize the healing process but have some drawbacks due to their allogeneic nature. Autologous fibrin sealants present several advantages. The aim of this study is to evaluate the performance of a new autologous fibrin sealant based on Endoret®PRGF® technology (E-sealant). One of the most widely used commercial fibrin sealants (Tisseel®) was included as comparative Control. E-sealant´s hematological and biological properties were characterized. The coagulation kinetics and the microstructure were compared. Their rheological profile and biomechanical behavior were also recorded. Finally, the swelling/shrinkage capacity and the enzymatic degradation of adhesives were determined. E-sealant presented a moderate platelet concentration and physiological levels of fibrinogen and thrombin. It clotted 30 s after activation. The microstructure of E-sealant showed a homogeneous fibrillar scaffold with numerous and scattered platelet aggregates. In contrast, Control presented absence of blood cells and amorphous protein deposits. Although in different order of magnitude, both adhesives had similar rheological profiles and viscoelasticity. Control showed a higher hardness but both adhesives presented a pseudoplastic hydrogel nature with a shear thinning behavior. Regarding their adhesiveness, E-sealant presented a higher tensile strength before cohesive failure but their elastic stretching capacity and maximum elongation was similar. While E-sealant presented a significant shrinkage process, Control showed a slight swelling over time. In addition, E-sealant presented a high enzymatic resorption rate, while Control showed to withstand the biodegradation process in a significant way. E-sealant presents optimal biochemical and biomechanical properties suitable for its use as a fibrin sealant with regenerative purposes.
Subject(s)
Hemostatics , Tissue Adhesives , Fibrin Tissue Adhesive/chemistry , Tissue Adhesives/chemistry , Regenerative Medicine , Hemostatics/chemistry , Wound HealingABSTRACT
BACKGROUND: A new fibrin adhesive made of buffalo plasma-derived fibrinogen and a thrombin-like snake venom enzyme, has been successfully used to immobilize free gingival grafts. This case series histologically compared sutured grafts (control group) with others immobilized by using the fibrin adhesive (experimental group). CASE DESCRIPTION: The grafts were placed in the contralateral mandibular bicuspids of 15 patients, so that each subject received one treatment of each type. Five biopsies of each group were collected at 7, 14 and 45 days of healing, which were histologically and morphometrically analyzed as regards the relative volume density of the different connective tissue components. RESULTS: The sites in the control group presented a higher inflammatory cell density at 7 days and a tendency towards a lower collagen density. In the experimental group, the grafts had an appearance of more advanced healing. Tissue maturity characteristics progressed until 14 and 45 days, but no difference between groups could be noted at these times. Conclusions: Within the limits of the present study, it may be suggested that the alternative fibrin adhesive tested could represent an alternative to sutures in gingival grafts procedures.
Subject(s)
Female , Humans , Male , Crotalid Venoms , Fibrin Tissue Adhesive/chemistry , Fibrin Tissue Adhesive/pharmacology , Gingiva/transplantation , Wound Healing/drug effects , Connective Tissue/anatomy & histology , Connective Tissue/blood supply , Epithelium/anatomy & histology , Epithelium/blood supply , Gingival Recession/surgery , Sutures , Thrombin , Time FactorsABSTRACT
Biosurgical preparations designed to promote surgical hemostasis and tissue adhesion are being increasingly employed across all surgical disciplines. Fibrin sealant is the most widely studied and utilized biosurgical adjunct in urology. Complex reconstructive, oncologic, and laparoscopic genitourinary procedures are those most appropriate for sealant use. This article details the diverse urologic applications of fibrin sealant in the management of genitourinary injuries, surgery, and complications.