Layer-by-Layer Coatings of Collagen-Hyaluronic acid Loaded with an Antibacterial Manuka Honey Bioactive Compound to Fight Metallic Implant Infections.

Implant-associated severe infections can result in catastrophic implant failures; thus, advanced antibacterial coatings are needed to combat infections. This study focuses on harnessing nature-inspired self-assembly of extracellular matrix (ECM)-like coatings on Ti alloy with a combination of jellyfish-derived collagen (J-COLL) and hyaluronic acid (HA) using our customized automated hybrid layer-by-layer apparatus. To improve the anti-infection efficacy of coatings, we have incorporated a natural antibacterial agent methylglyoxal (MGO, a Manuka honey compound) in optimized multilayer coatings. The obtainment of MGO-loaded multilayer coatings was successfully assessed by profilometry, contact angle, attenuated total reflectance (ATR)-Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. In vitro degradation confirmed the controlled release activity of MGO with a range of concentrations from 0.90 to 2.38 mM up to 21 days. A bacterial cell culture study using Escherichia coli (E. coli) and Staphylococcus epidermidis (S. epidermidis) confirmed that the MGO incorporated within layers 7 and 9 had a favorable effect on preventing bacterial growth and colonization on their surfaces. An in vitro cytocompatibility study confirmed that MGO agents included in the layers did not affect or reduce the cellular functionalities of L929 fibroblasts. In addition, MGO-loaded layers with Immortalized Mesenchymal Stem Cells (Y201 TERT-hMSCs) were found to favor the growth and differentiation of Y201 cells and promote calcium nodule formation. Overall, these surface coatings are promising candidates for delivering antimicrobial activity with bone-inducing functions for future bone tissue engineering applications.

An injectable liposome-anchored teriparatide incorporated gallic acid-grafted gelatin hydrogel for osteoarthritis treatment.

Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1-34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1-34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1ß-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.

Bone-Targeting Liposome-Encapsulated Salvianic Acid A Improves Nonunion Healing Through the Regulation of HDAC3-Mediated Endochondral Ossification.

AIM: Nonunion is a major complication in fracture repair and remains a challenge in orthopaedics and trauma surgery. In this study, we aimed to evaluate the effectiveness of treatment of nonunion with a large radial defect using a bone-targeting liposome-encapsulated salvianic acid A (SAA-BTL)-incorporated collagen sponge and further elucidate whether the effects were closely related to histone deacetylase 3 (HDAC 3)-mediated endochondral ossification in nonunion healing process. METHODS: Fifteen New Zealand female rabbits were randomly divided into three groups. Segmental radius critical size defects (15 mm) were created via surgery on both the forelimbs of the rabbits. The SAA-BTL/SAA/saline-incorporated collagen sponges were implanted into the defects in the three groups, respectively, for four weeks of treatment. X-ray imaging, micro-computed tomography (CT) analysis, histology, and immunofluorescence analysis (HDAC3, collagen II, VEGFA, and osteocalcin) were performed to determine the effects of the treatments. In addition, a short interfering RNA was applied to induce HDAC3 knockdown in the chondrogenic cell line ATDC5 to investigate the roles of HDAC3 and SAA intervention in endochondral ossification in nonunion healing. RESULTS: X-ray imaging and micro-CT results revealed that SAA-BTL-incorporated collagen sponges significantly stimulated bone formation in the nonunion defect rabbit model. Furthermore, immunofluorescence double staining and histology analysis confirmed that SAA-BTL significantly increased the expression of P-HDAC3, collagen II, RUNX2, VEGFA, and osteocalcin in vivo; accelerated endochondral ossification turnover from cartilage to bone; and promoted long bone healing of nonunion defects. ATDC5 cells knocked down for HDAC3 showed significantly decreased expression of HDAC3, which resulted in reduced expression of chondrogenesis, osteogenesis, and angiogenesis biomarker genes (Sox9, Col10a1, VEGFA, RUNX2, and Col1a1), and increased expression of extracellular matrix degradation marker (MMP13). SAA treatment reversed these effects in the HDAC3 knockdown cell model. CONCLUSION: SAA-BTL can improve nonunion healing through the regulation of HDAC3-mediated endochondral ossification.