Orthopedic and dental implants are increasingly used in the medical field in view of their high success rates. Implant-associated infections, however, still occur and are difficult to treat. To combat these infections, the application of an active coating to the implant surface is advocated as an effective strategy to facilitate sustained release of antibacterial drugs from implant surfaces. Control over this release is, however, still a major challenge. To overcome this problem, we deposited composite coatings composed of a chitosan matrix containing gelatin nanospheres loaded with antibiotics onto stainless steel plates by means of the electrophoretic deposition technique. The gelatin nanospheres were distributed homogeneously throughout the coatings. The surface roughness and wettability of the coatings could be tuned by a simple adjustment of the weight ratio between the gelatin nanospheres and chitosan. Vancomycin and moxifloxacin were released in sustained and burst-type manners, respectively, while the coatings were highly cytocompatible. The antibacterial efficacy of the coatings containing different amounts of antibiotics was tested using a zone of inhibition test against Staphylococcus aureus, which showed that the coatings containing moxifloxacin exhibited an obvious inhibition zone. The coatings containing a high amount of vancomycin were able to kill bacteria in direct contact with the implant surface. These results suggest that the antibacterial capacity of metallic implants can be tuned by orthogonal control over the release of (multiple) antibiotics from electrophoretically deposited composite coatings, which offers a new strategy to prevent orthopedic implant-associated infections.

Implant surface properties are a key factor in bone responses to metallic bone implants. In view of the emerging evidence on the important role of osteoclasts in bone regeneration, we here studied how surface roughness affects osteoclastic differentiation and to what extent these osteoclasts have stimulatory effects on osteogenic differentiation of osteoprogenitor cells. For this, we induced osteoclasts derived from RAW264.7 cell line and primary mouse macrophages on titanium surfaces with different roughness (Ra 0.02–3.63 μm) and analyzed osteoclast behavior in terms of cell number, morphology, differentiation, and further anabolic effect on osteoblastic cells. Surfaces with different roughness induced the formation of osteoclasts with distinct phenotypes, based on total osteoclast numbers, morphology, size, cytoskeletal organization, nuclearity, and osteoclastic features. Furthermore, these different osteoclast phenotypes displayed differential anabolic effects toward the osteogenic differentiation of osteoblastic cells, for which the clastokine CTHRC1 was identified as a causative factor. Morphologically, osteoclast potency to stimulate osteogenic differentiation of osteoblastic cells was found to logarithmically correlate with the nuclei number per osteoclast. Our results demonstrate the existence of a combinatorial effect of surface roughness, osteoclastogenesis, and osteogenic differentiation. These insights open up a new dimension for designing and producing metallic implants by considering the implant roughness to locally regulate osseointegration through coupling osteoclastogenesis with osteogenesis.

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Existing local drug delivery systems for periodontitis suffer from poor antibacterial effect and unsatisfied periodontal regeneration. In this study, a smart gingipain-responsive hydrogel (PEGPD@SDF-1) was synthesized as an environmentally sensitive carrier for on-demand drug delivery. The PEGPD@SDF-1 hydrogel was synthesized from polyethylene glycol diacrylate (PEG-DA) based scaffolds, dithiothreitol (DTT), and a novel designed functional peptide module (FPM) via Michael-type addition reaction, and the hydrogel was further loaded with stromal cell derived factor-1 (SDF-1). The FPM exhibiting a structure of anchor peptide−short antimicrobial peptide (SAMP)− anchor peptide could be cleaved by gingipain specifically, and the SAMP was released out of the hydrogel for antibacterial effect in response to gingipain. The hydrogel properties were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), swelling ratio analysis, degradation evaluation, and release curve description of the SAMP and SDF-1. Results in vitro indicated the PEGPD@SDF-1 hydrogel exhibited preferable biocompatibility and could promote the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Antibacterial testing demonstrated that the PEGPD@SDF-1 hydrogel released the SAMP stressfully in response to gingipain stimulation, thereby strongly inhibiting the growth of Porphyromonas gingivalis. Furthermore, the study in vivo indicated that the PEGPD@SDF-1 hydrogel inhibited P. gingivalis reproduction, created a low-inflammatory environment, facilitated the recruitment of CD90+/CD34− stromal cells, and induced osteogenesis. Taken together, these results suggest that the gingipain-responsive PEGPD@SDF-1 hydrogel could facilitate in situ periodontal tissue regeneration and is a promising candidate for the on-demand local drug delivery system for periodontitis.