Abstract
Microbial infections occurring during bone surgical treatment, the cause of osteomyelitis and implant failures, are still an open challenge in orthopedics. Conventional therapies are often ineffective and associated with serious side effects due to the amount of drugs administered by systemic routes. In this study, a medicated osteoinductive and bioresorbable bone graft was designed and investigated for its ability to control antibiotic drug release in situ. This represents an ideal solution for the eradication or prevention of infection, while simultaneously repairing bone defects. Vancomycin hydrochloride and gentamicin sulfate, here considered for testing, were loaded into a previously developed and largely investigated hybrid bone-mimetic scaffold made of collagen fibers biomineralized with magnesium doped-hydroxyapatite (MgHA/Coll), which in the last ten years has widely demonstrated its effective potential in bone tissue regeneration. Here, we have explored whether it can be used as a controlled local delivery system for antibiotic drugs. An easy loading method was selected in order to be reproducible, quickly, in the operating room. The maintenance of the antibacterial efficiency of the released drugs and the biosafety of medicated scaffolds were assessed with microbiological and in vitro tests, which demonstrated that the MgHA/Coll scaffolds were safe and effective as a local delivery system for an extended duration therapy—promising results for the prevention of bone defect-related infections in orthopedic surgeries.
Highlights
Regenerative medicine aims to restore loss of tissue and organ functionality resulting from injury, aging, or diseases [1,2]
Tissues are able to constantly self-repair after injury, but when lesions have critical dimensions, biomaterials and 3D bone grafts are required to play a key role in the stimulation of autologous cells toward damaged tissue regeneration and their functions restoration. 3D scaffolds must be properly designed with a bonemimetic chemistry and endowed with specific morphological requirements, such as a well-defined 3D macro and microarchitecture with an interconnected porous network, in order to facilitate promotion and support of the entire regenerative process [3,4]
The purpose of this study is to establish the suitability of previously developed, fully bioresorbable bone-hybrid scaffolds made from type I collagen, biomineralized with bioresorbable Mg-doped hydroxyapatite (MgHA), by loading them with drugs and preserving the activity thereof, in order to demonstrate their effectiveness as a supplier of local therapy to prevent bone infection
Summary
Regenerative medicine aims to restore loss of tissue and organ functionality resulting from injury, aging, or diseases [1,2]. Pharmaceutics 2021, 13, 1090 a biomimetic approach that allowed for obtaining a composition perfectly matching that of the damaged tissue, and which had previously and significantly demonstrated its potential in bone regeneration [5,6,7] This family of biomimetic scaffolds recreates, in vivo, a functional microenvironment that can recruit autologous cells and stimulate the whole regenerative process. These well integrated systems, when implanted, can facilitate the growth of microbes having the potential to adhere on the material and develop biofilms, which can cause implant failure This type of infection, involving orthopedic devices, can potentially lead to a wide variety of complications, the most conspicuous disease of which is osteomyelitis, which occurs in 2–5% of surgeries [8,9]. Their toxicity excludes the possibility of increasing their dosage to avoid secondary effects and reduce the impact of resistance in the target bacteria
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