Page 73 - IJB-9-3

International Journal of Bioprinting 3DP hydrogels to combat antibiotic-resistant bacteria

devices range from 5% to 10%, and open fractures with the polymerization process of the cement . Therefore,
[12]
these devices show even higher rates up to 30% . The alternative biomaterials incorporating Rif and other
[1]
majority of infections caused by orthopedic devices are antibiotics have been investigated. Darouiche et al.
brought on by opportunistic pathogens and bacteria found described the in vivo local efficacy of a combination
in the skin microbiota . The biofilm-forming species of minocycline with Rif sprayed onto titanium pins as
[2]
Staphylococcus aureus and Staphylococcus epidermidis are a prophylactic implant coating . Later, Inzana et al.
[13]
the most common pathogens related to implant-associated developed a 3D-printed biomaterial system with a dual
infections [2-4] . Staphylococci can attach to and colonize the antibiotic delivery system of Rif and Van to treat an
implant surface and surrounding tissue forming a biofilm established bone biofilm infection .
[14]
structure, thereby becoming less susceptible to antibiotics
and immune defenses because the antibiotics and immune Furthermore, Sanz-Ruiz et al. developed a system with
defenses cannot correctly penetrate the biofilm and target Rif microcapsules of alginate that can be incorporated into
[15]
the bacteria [2,5] . bone cement in combination with other antibiotics .
However, these solutions have some limitations, such as
Clinically, implant infections are mainly prevented by limited control over the release profile of the drug and not
the application of skin antiseptics, such as iodine povidone suitable for 3D bioprinting (3D printing of living cells) in
or chlorhexidine, and systemic antibiotic prophylaxis, such bone regeneration therapies. Furthermore, 3D printing
as intravenous administration of cefazolin 30 to 60 min technology allows personalized geometries specifically
before the surgical procedure . Despite the reduction for the necessity of the patient . Additive manufacturing
[1]
[16]
of infection rates, systemic antibiotic prophylaxis and (AM) technology, also known as 3D printing, increases
antiseptics cannot provide sufficient protection on the the possibility for creating orthopedic devices with
surgical wound in all cases. When compared to systemic more combinations of biomaterials and antimicrobial
administration, local antibiotic prophylaxis provides a compounds with a controlled drug release profile.
higher local antibiotic concentration and bioavailability, at
the bone site, with minimum toxicity effects [6,7] . The existing standard for 3D printing in biomedical
research is the “ISO/ASTM 52900 Standard Terminology
Poly (methyl methacrylate) (PMMA), also known as for Additive Manufacturing – General Principles –
bone cement, is one of the most typical biomaterials applied Terminology” . This standard defines the seven
[17]
in orthopedics as a local antibiotic delivery system . The standard 3D printing types: binder jetting [18,19] , direct
[1]
surgeon usually mixes the PMMA powder with antibiotics, energy deposition , material extrusion (mechanical
[20]
such as gentamicin sulfate, tobramycin, or vancomycin and pneumatic) [21,22] , material jetting (inkjet, microvalve,
(Van), to obtain a paste. Then, the surgeon applies the paste laser-assisted, acoustic, and PolyJet) [23,24] , powder bed
as a coating of bone or joint implantable devices, or as a fusion (selective laser sintering, selective laser melting,
spacer in infection treatment revision surgery. However, direct metal printing, and electron beam melting) , sheet
[25]
bone cement is not biodegradable, shows poor antibiotic lamination (laminated object manufacturing) , and vat
[26]
release profiles, and can only be combined with a limited photopolymerization (stereolithography apparatus and
number of antimicrobial compounds . In many cases, only direct light processing) [27,28] . In this work, the material
[8]
a single antibiotic is used for local delivery, and in view extrusion (pneumatic) technology was selected for its
of the poor release profile of the antibiotic, an increased ability to create softer biomaterials, like hydrogels, that can
risk of resistance development is inevitable. For example, be applied in bone regeneration , especially in joints, or as
[29]
the exposure of S. aureus or Pseudomonas aeruginosa a coating on orthopedic implants .
[30]
to antibiotics such as rifampicin (Rif) or ciprofloxacin
is related to a high risk of resistance development [9,10] . Hydrogels have been deeply investigated for their
For that reason, it is not advisable to administer Rif as a application in bone tissue engineering because of
monotherapy. A combination of antibiotics incorporated in their porosity, degradation properties, and high-water
the biomaterial will reduce the risk of selection of resistant content [31,32] . In recent years, gelatin methacrylate
bacteria to one antibiotic and will thereby eradicate the (GelMA) hydrogels have been studied in tissue
infection. For example, Rif is an essential antibiotic used engineering for bone regeneration applications because
in combination with other antibiotics such as Van, or of their high biocompatibility and the possibility of being
with both Van and gentamicin sulfate, for the treatment photochemically crosslinked, which enable the formation
[33]
of bacterial biofilm bone implant infection attributed to of a stable gel at physiological temperature . In addition,
its ability to penetrate and destroy the bacterial biofilm . GelMA hydrogels have promising bioink characteristics
[11]
Unfortunately, Rif cannot be used in bone cement since for 3D printing, which is necessary to create scaffolds with
it acts as a free radical neutralizer and negatively affects different porosities and geometries to incorporate cells or

Volume 9 Issue 3 (2023) 65 https://doi.org/10.18063/ijb.683