Mechanically Activated Extracellular Vesicle Functionalised Melt Electrowritten Materials for Bone Regeneration: A Mechano-Biomimetic Scaffold

Mechanobiological cues arising directly via tissue/scaffold mechanics or indirectly via mechanically activated cell secretomes represent potent stimuli that mediate cell behaviour and tissue adaptation. Exploiting these cues in regeneration strategies holds great promise for tissue repair. In this study, we harness indirect biophysical cues originating from osteocytes in a combination with direct biophysical cues from Melt ElectroWritten (MEW) scaffolds to form a single engineered construct with the aim of synergistically enhancing osteogenesis. The secretome of mechanically activated osteocytes was collected within conditioned media (CM) and extracellular vesicles (EV) were subsequently isolated. Building on MEW micro-fibrous scaffolds with controlled microarchitecture and mineral nanotopography optimised for bone repair, a protocol was developed to functionalise these materials with CM or EVs. Human MSC proliferation was enhanced in both CM and EV functionalised scaffolds. EV functionalised scaffolds were further found to significantly enhance MSC osteogenesis, with enhanced alkaline phosphatase expression, collagen production, and mineralisation compared to control scaffolds. Furthermore, enhanced formation of mineralised nodules was identified in EV functionalised materials. Combining direct biophysical cues provided by the fibrous architecture/mineral nanotopography with the indirect cues provided by EVs, these constructs hold great promise to enhance the repair of damaged bone in a physiologically relevant manner.

Synthesis and Characterization of Bone Binding Antibiotic-1 (BBA-1), a Novel Antimicrobial for Orthopedic Applications

Osteomyelitis and orthopedic infections are major clinical problems, limited by a lack of antibiotics specialized for such applications. In this paper, we describe the design and synthesis of a novel bone-binding antibiotic (BBA-1) and its subsequent structural and functional characterization. The synthesis of BBA-1 was the result of a two-step chemical conjugation of cationic selective antimicrobial-90 (CSA-90) and the bisphosphonate alendronate (ALN) via a heterobifunctional linker. This was analytically confirmed by HPLC, FT-IR, MS and NMR spectroscopy. BBA-1 showed rapid binding and high affinity to bone mineral in an in vitro hydroxyapatite binding assay. Kirby—Baur assays confirmed that BBA-1 shows a potent antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus comparable to CSA-90. Differentiation of cultured osteoblasts in media supplemented with BBA-1 led to increased alkaline phosphatase expression, which is consistent with the pro-osteogenic activity of CSA-90. Bisphosphonates, such as ALN, are inhibitors of protein prenylation, however, the amine conjugation of ALN to CSA-90 disrupted this activity in an in vitro protein prenylation assay. Overall, these findings support the antimicrobial, bone-binding, and pro-osteogenic activities of BBA-1. The compound and related agents have the potential to ensure lasting activity against osteomyelitis after systemic delivery.

INVESTIGATION OF ALKALINE PHOSPHATASE EXPRESSION IN THE SMALL INTESTINES OF THE BRONZE TURKEY (MELEAGRIS GALLOPAVO)

The aim of our investigation was to study the expression of the enzyme Alkaline phosphatase in the small intestines of the bronze turkey in the age aspect. Forty clinically healthy bronze turkeys (twenty males and twenty females) were studied. The groups of the birds were at age 1, 7, 14, 28, 35, 49, 56, 90, 120, and 240 days. Each group consisted of five males and five female birds. The enzyme’s expression was investigated by Gomori staining. The most significant expression of tissue alkaline phosphatase was observed in the epithelial cells of the duodenum. It was weaker in the jejunum and weakest in the ileum. In the three intestinal segments, high enzyme activity was observed during the first weeks of hatching (from the 1st to the 14th day in the duodenum and ileum, and from the 1st to the 28th day in the jejunum).

The mussel-inspired assisted apatite mineralized on PolyJet material for artificial bone scaffold

With the development of three-dimensional (3D) printing, many commercial 3D printing materials have been appliedin the fields of biomedicine and medical. MED610 is a clear, biocompatible PolyJet material that is medically certified forbodily contact. In this study, the polydopamine (PDA)/hydroxyapatite (HA) coating was added to the printed MED610 objectsto evaluate its physical properties, cell proliferation, cell morphology, and alkaline phosphatase expression level. The resultsshow that the PDA/HA coating helps printed objects to enhance the hardness, biocompatibility, and osteogenic differentiationpotential. We expect that PDA/HA coatings contribute to the applicability of MED610 in biomedical and medical applications