To prevent surgical site infections, antibiotics can be released from carriers made of biomaterials, such as collagen, that support the healing process and are slowly degraded in the body. In our labs we have developed collagen laminates that can be easily assembled and bonded on-site, according to medical needs. As shown previously, the asymmetric assembly leads to different release rates at the major faces of the laminate. Since the pH changes during the wound healing and infection, we further examined the effect of an acidic and alkaline pH, in comparison to pH 7.4 on the release of vancomycin from different collagen samples. For this purpose, we used an additively manufactured sample holder and quantified the release by HPLC. Our results show that the pH value does not have any influence on the total amount of released vancomycin (atelocollagen sponge pH 5.5: 71 ± 2%, pH 7.4: 68 ± 8%, pH 8.5: 74 ± 3%, bilayer laminate pH 5.5: 61 ± 6%, pH 7.4: 69 ± 4% and pH 8.5: 67 ± 3%) but on the time for half-maximal release. At an acidic pH of 5.5, the swelling of the atelocollagen sponge is largely increased, leading to a 2–3 h retarded release, compared to the physiological pH. No changes in swelling were observed at the basic pH and the compound release was 1–2 h delayed. These effects need to be considered when choosing the materials for the laminate assembly.
The controlled release of antibiotics prevents the spread of pathogens and thereby improves healing processes in regenerative medicine. However, high concentrations may interfere with healing processes. It is therefore advantageous to use biodegradable materials for a controlled release. In particular, multilayer materials enable differential release at different surfaces. For this purpose, collagen sheets of different properties can be bonded by photochemical crosslinking. Here, we present the development and application of an easily accessible, additively manufactured sample holder to study the controlled release of vancomycin from modularly assembled collagen laminates in two directions. As proof-of-concept, we show that laminates of collagen sheets covalently linked by rose bengal and green light crosslinking (RGX) can be tightly inserted into the device without leakage from the upper to lower cavity. We used this sample holder to detect the release of vancomycin from symmetrically and asymmetrically loaded two-layer and three-layer collagen laminates into the upper and lower cavity of the sample holder. We show that these collagen laminates are characterized by a collagen type-dependent vancomycin release, enabling the control of antibiotic release profiles as well as the direction of antibiotic release.
1 May 2021 in Journal of Pharmacological and Toxicological Methods