Versatile Biomaterial Additive: A Game‐Changing Multifunctional Synthetic Peptide With Pro‐Regenerative, Anti‐Inflammatory, and Antibacterial Properties

The prevalence of bone disorders and deformities is increasing due to trauma, malignant neoplasms, infections, and degenerative and inflammatory diseases. Bone repair and replacement have evolved as a consequence of advancements in orthopedic technology and biomaterials with enhanced properties. The rapid growth of the bone tissue engineering field is being significantly influenced by biomaterials, such as polymer scaffolds with appropriate surface modifications. New additives are constantly being developed in response to the increasing demand for enhancing the bioactivity of biocomposites used for bone regeneration. We present the design and synthesis of a synthetic bioactive peptide UG46, which is multifunctional and consists of the fragment of human Cystatin C (CystC) and anoplin. In addition, the peptide is assessed as an additive that is employed to enhance the repair of bone by enriching porous chitosan (CH) scaffolds. Our results indicated that the UG46 peptide possesses pro-regenerative properties, while it did not exhibit any cytotoxic effects on human osteoblasts or human fibroblasts. Incubation of cells with CH and CH-UG46 extracts significantly increased cell proliferation, cell proliferation over 200% of control cells. Even though the proliferation assay revealed a significant inhibition of cell proliferation in cells seeded directly on the composites, the beneficial effect of the UG46 peptide was still noticeable. Additionally, the UG46 peptide exhibited dose-dependent anti-inflammatory properties in both its free form and as a biocomposite additive, qualifying it as a promising candidate for a bone biomaterial component. The working concentrations of UG46 peptide have been established at 40-80 μg/mL. The molecular structure analysis of the CH-UG46 biocomposites revealed that the majority of the pores were sufficiently large to enable osteoblast cells to infiltrate the scaffold, while concurrent microporosity (< 20 μm) enabled cell infiltration, vascularization, and cell-matrix interactions. Additionally, the peptide alone exhibits limited antibacterial properties; however, the peptide released from the CH-UG46 biocomposite at high levels has been demonstrated to be capable of inhibiting the growth of the selected bacterial strains that are most frequently found infecting healing wounds by over 83% for all strains tested stains with A. baumani bacterial count reduction at 99.86%. Our findings indicate that the bioactive peptide we have proposed is a promising enhancement for porous scaffolds. It has the potential to facilitate the creation of specialized, custom-designed biomaterials with multifunctional properties, including healing, defense, and hygiene.