The aim of the study was to develop an orthopedic implant coating in the form of vancomycin-loaded collagen/hydroxyapatite layers (COLHA+V) that combine the ability to prevent bone infection with the ability to promote enhanced osseointegration. The ability to prevent bone infection was investigated employing a rat model that simulated the clinically relevant implant-related introduction of bacterial contamination to the bone during a surgical procedure using a clinical isolate of Staphylococcus epidermidis. The ability to enhance osseointegration was investigated employing a model of a minipig with terminated growth. Six weeks following implantation, the infected rat femurs treated with the implants without vancomycin (COLHA+S. epidermidis) exhibited the obvious destruction of cortical bone as evinced via a cortical bone porosity of up to 20% greater than that of the infected rat femurs treated with the implants containing vancomycin (COLHA+V+S. epidermidis) (3%) and the non-infected rat femurs (COLHA+V) (2%). The alteration of the bone structure of the infected COLHA+S. epidermidis group was further demonstrated by a 3% decrease in the average Ca/P molar ratio of the bone mineral. Finally, the determination of the concentration of vancomycin released into the blood stream indicated a negligible systemic load. Six months following implantation in the pigs, the quantified ratio of new bone indicated an improvement in osseointegration, with a two-fold bone ingrowth on the COLHA (47%) and COLHA+V (52%) compared to the control implants without a COLHA layer (27%). Therefore, it can be concluded that COLHA+V layers are able to significantly prevent the destruction of bone structure related to bacterial infection with a minimal systemic load and, simultaneously, enhance the rate of osseointegration.

• Keywords
• Staphylococcus epidermidis, bone, collagen, hydroxyapatite, implant-related bone infection, minipig, orthopedic implant, osseointegration, rat, vancomycin,
• Publication type
• Journal Article MeSH

The study presents a novel vancomycin-releasing collagen wound dressing derived from Cyprinus carpio collagen type I cross-linked with carbodiimide which retarded the degradation rate and increased the stability of the sponge. Following lyophilization, the dressings were subjected to gamma sterilization. The structure was evaluated via scanning electron microscopy images, micro-computed tomography, and infrared spectrometry. The structural stability and vancomycin release properties were evaluated in phosphate buffered saline. Microbiological testing and a rat model of a wound infected with methicillin-resistant Staphylococcus aureus (MRSA) were then employed to test the efficacy of the treatment of the infected wound. Following an initial mass loss due to the release of vancomycin, the sponges remained stable. After 7 days of exposure in phosphate buffered saline (37°C), 60% of the material remained with a preserved collagen secondary structure together with a high degree of open porosity (over 80%). The analysis of the release of vancomycin revealed homogeneous distribution of the antibiotic both across and between the sponges. The release of vancomycin was retarded as proved by in vitro testing and further confirmed by the animal model from which measurable concentrations were observed in blood samples 24 hours after the subcutaneous implantation of the sponge, which was more than observed following intraperitoneal administration. The sponge was also highly effective in terms of reducing the number of colony-forming units in biopsies extracted from the infected wounds 4 days following the inoculation of the wounds with the MRSA solution. The presented sponges have ideal properties to serve as wound dressing for prevention of surgical site infection or treatment of already infected wounds.

• MeSH
• Anti-Bacterial Agents pharmacokinetics   MeSH
• Wound Healing drug effects   MeSH
• Carps MeSH
• Carbodiimides pharmacokinetics   MeSH
• Collagen pharmacokinetics   MeSH
• Rats MeSH
• Methicillin-Resistant Staphylococcus aureus drug effects   MeSH
• Bandages MeSH
• Vancomycin pharmacokinetics   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Carbodiimides MeSH
• Collagen MeSH
• Vancomycin MeSH

This review provides a summary of recent research on biomimetic and bioinspired strategies applied in the field of biomedical material engineering and focusing particularly on calcium phosphate-protein template constructs inspired by biomineralisation. A description of and discussion on the biomineralisation process is followed by a general summary of the application of the biomimetic and bioinspired strategies in the fields of biomedical material engineering and regenerative medicine. Particular attention is devoted to the description of individual peptides and proteins that serve as templates for the biomimetic mineralisation of calcium phosphate. Moreover, the review also presents a description of smart devices including delivery systems and constructs with specific functions. The paper concludes with a summary of and discussion on potential future developments in this field.

• Keywords
• biomimetic, calcium phosphate, protein template,
• Publication type
• Journal Article MeSH
• Review MeSH