Bone defects and fractures present significant clinical challenges, particularly in orthopedic and maxillofacial applications. While minor bone defects may be capable of healing naturally, those of a critical size necessitate intervention through the use of implants or grafts. The utilization of traditional methodologies, encompassing autografts and allografts, is constrained by several factors. These include the potential for donor site morbidity, the restricted availability of suitable donors, and the possibility of immune rejection. This has prompted extensive research in the field of bone tissue engineering to develop advanced synthetic and bio-derived materials that can support bone regeneration. The optimal bone substitute must achieve a balance between biocompatibility, bioresorbability, osteoconductivity, and osteoinductivity while simultaneously providing mechanical support during the healing process. Recent innovations include the utilization of three-dimensional printing, nanotechnology, and bioactive coatings to create scaffolds that mimic the structure of natural bone and enhance cell proliferation and differentiation. Notwithstanding the advancements above, challenges remain in optimizing the controlled release of growth factors and adapting materials to various clinical contexts. This review provides a comprehensive overview of the current advancements in bone substitute materials, focusing on their biological mechanisms, design considerations, and clinical applications. It explores the role of emerging technologies, such as additive manufacturing and stem cell-based therapies, in advancing the field. Future research highlights the need for multidisciplinary collaboration and rigorous testing to develop advanced bone graft substitutes, improving outcomes and quality of life for patients with complex defects.

Background: Hemostasis plays a crucial role during every surgery allowing for a bloodless operating field. Fast and effective surgery leads to a reduced risk of postoperative complications. One of the latest methods for achieving homeostasis is using natural polysaccharide-based hemostatic powders. The study aimed to evaluate the biocompatibility according to the ISO 10993 standards of 4SEAL® Hemostatic powder. Methods: Chemical characterization (Headspace GC-MS, GC-MS, and ICP-MS), cytotoxicity, genotoxicity (MLA and AMES), endotoxin contamination, sensitization potential, intracutaneous reactivity, acute and subacute systemic toxicity with implantation, and pyrogenicity were evaluated to investigate the biocompatibility of the 4SEAL® Hemostatic powder. Studies were conducted according to ISO 10993 standards. Results: The biocompatibility requirements according to ISO 10993-1 for 4SEAL® Hemostatic powder were met. Based on the conducted in-vitro studies, 4SEAL® Hemostatic powder shows a non-cytotoxicity and non-mutagenic potential. Also, the results of in vivo studies of 4SEAL® Hemostatic powder shows no signs of toxicity, non-sensitizing, non-irritating, and no pyrogenicity potential. In the chemical characterization of 4Seal® Hemostatic Powder, no compounds were identified above Analytical Evaluation Threshold (AET) and no elements with concentrations higher than element-specific PDE [μg/day] were detected. Conclusions: 4SEAL® Hemostatic powder is a promising new hemostatic agent with a wide range of potential applications and excellent biocompatibility.

Background: Hemorrhage, a sudden and severe leakage of blood due to the disruption of blood vessels, is one of the most common causes of death from injuries worldwide. Severe bleeding accounts for more than 35% of pre-hospital deaths and about 40% of deaths recorded within 24 hours of injury. One of the methods for achieving homeostasis is the use of hemostatic powders. This study compares the basic safety and performance of the most popular hemostatic powders. Methods: Basic safety of commercially available products were evaluated using MTT, MEM elution assay, and endotoxin testing. The in vitro performance was evaluated using water absorption capacity, water absorption rate, and adhesion strength assays. Results: 4Seal, Starsil, and 4DryField extracts did not cause cytotoxicity in MTT and MEM elution assays. PerClot and SuperClot extracts demonstrated cytotoxic potential in MTT assay, while Arista extract was cytotoxic in both MEM elution and MTT assays. 4Seal has the lowest endotoxin contamination, followed by PerClot, 4DryField, SuperClot, Arista, and Starsil. 4Seal and Starsil showed significantly highest WAR among the tested samples, followed by 4DryField, Arista, PerClot, and SuperClot. Adhesion force is highest for 4Seal, followed by Starsil, PerClot, 4DryField Arista, and SuperClot. Conclusion: 4Seal is the most versatile in terms of safety and functional properties compared to 4DryField, Arista, PerClot, Starsil, and SuperClot.

Many medical procedures could benefit from the use of tissue sealants which allow for reduced surgery time, limited blood loss, easier tissue handling, and fewer postoperative complications. The safety and biocompatibility of surgical sealants are of paramount importance therefore, the aim of this study is to investigate the biocompatibility of NE’X Glue Surgical Adhesive. Chemical characterization (VOC and elements), cytotoxicity (MEM elution), genotoxicity (AMES and MLA), endotoxin contamination, sensitization potential, intracutaneous reactivity, acute and subchronic systemic toxicity with implantation as well as pyrogenicity were evaluated to investigate the biocompatibility of the NE’X Glue Surgical Adhesive. Studies were conducted according to ISO 10993 standards. The biocompatibility requirements with accordance to ISO 10993-1 for NE'X Glue were met. In vitro studies showed that NE'X Glue surgical adhesive is non-cytotoxic and non-mutagenic. Also, in vivo studies demonstrated that NE'X Glue shows no signs of toxicity, has no pyrogenic potential, and is non-sensitizing and non-irritating. The chemical characterization showed that no compounds were identified above Analytical Evaluation Threshold (AET), and no elements with concentrations higher than element-specific PDE (µg/day) were detected. NE'X Glue Surgical Adhesive is a versatile and promising new surgical sealant with a wide range of potential applications and very good biocompatibility.

Tissue adhesives are an alternative to conventional surgical sutures to reduce the time and cost of wound closure and to improve patient comfort. The use of tissue adhesives does not require any subsequent intervention and significantly lowers the volume and rate of blood loss, and reduces the need for transfusions during and after surgery. However, based on their formulation, tissue adhesives’ safety profile and functional properties may differ. Therefore, this study aimed to evaluate the basic safety and performance of NE’X Glue® Surgical Sealant, BioGlue® Surgical Sealant, and PREVELEAK^TM Surgical Sealant in vitro. The basic safety of commercially available tissue adhesives was evaluated using MEM elution assay according to ISO 10993–5 and endotoxin level according to 85. USP. The in vitro performance was evaluated using lap-shear by tension loading test, burst strength test, degradation, and swelling assays. NE’X Glue®, BioGlue®, and PREVELEAK^TM did not cause cytotoxicity in MEM elution assay. All surgical adhesives are below the general limit of endotoxin contamination of 20 EU/device. NE’X Glue® and BioGlue® showed the highest and comparable strength properties in lap shear and burst strength tests compared to PREVELEAK^TM. NE’X Glue® and PREVELEAK^TM are characterized by lower degradation potential than BioGlue®. PREVELEAK^TM is characterized by the highest swelling when compared to NE’X Glue® and BioGlue®. NE’X Glue® is most versatile in terms of functional properties while maintaining the same safety profile as BioGlue® and PREVELEAK^TM.