Page 63 - IJB-9-5

International Journal of Bioprinting 3D-printed PLA-BG composite induces angiogenesis

1. Introduction BG up to 20% (w/w). This material was suitable to print
complex, porous, and finely structured scaffolds using
Large bone defects that occur after trauma or resections standard Cartesian 3D printers. In the first step, the porous
due to cancer still are a challenge for surgeons. Often structure of the material was described, and the mechanical
these defects do not heal without supportive therapy, and stability was proven , showing the potential of this new
[16]
consequently, the risk to develop nonunions is immense. material. We demonstrated an even distribution of the BG
Autologous bone grafting is the gold standard of therapy for particles within the PLA matrix and a prolonged release
this condition; however, this therapy not only necessitates of calcium from this material, which increased with BG
subsequent surgeries for the patient, but is also associated concentrations. Adhesion of mesenchymal stem cells
with side effects and high costs. Moreover, the amount of (MSC) and their osteogenic as well as anti-inflammatory
[1]
material is limited . Although some other therapies like properties increased with increasing BG content of the
reamer-arrigator-aspirator (RIA) systems are getting more composite. Accordingly, whole blood stimulation assays
[2]
and more important , main challenge in this area is to find followed by protein array analysis revealed no significant
a suitable alternative to the gold-standard therapy, which is inflammatory potential [17,18] . A BG concentration-
highly risky.
dependent calcium release from this material [17,16] mediates
One option is to use biomaterials manufactured by 3D at least some of the observed effects .
[18]
printing. Many 3D-printable biopolymers like polylactic
acid (PLA), polycaprolacton (PCP), poly lactide-co- Thus, this 3D-printed material fulfills most of the
glycolide (PGLA), or others are suitable for applications requirements as described in the diamond concept of
in bone tissue engineering as they are biocompatible, bone healing—being osteoinductive, osteogenetic, and
[19]
biodegradable, and mechanically stable, but they are not mechanically stable . However, the question remains
bioactive . One possibility is to combine these materials, as to whether it also meets the requirements concerning
[3]
[20]
for example, polylactide, with bioactive materials like angiogenesis . Bone fracture healing is a multifactorial
hydroxyapatite (HA) , tricalcium phosphate (TCP) , process, with angiogenesis being a key aspect. Without
[4]
[5]
or bioglass (BG) , resulting in composite demonstrating vascularization of the implanted biomaterial, neither bone
[6]
[21,22]
high osteoconductivity and osteoinductive properties, healing nor any tissue regeneration can take place .
which are however not printable by themselves. Especially, Known factors involved in formation of vasculature are,
bioglass is an interesting ionic compound in this context. for example, stromal derived factor-1 (SDF-1) and vascular
Bioactive glasses were discovered in 1969 and represent endothelial growth factor (VEGF), which also regulate
[22,23]
an interesting alternative implant material. 45S5 bioglass the neoangiogenesis of newly formed bone . Further
(BG) has already been used clinically as it stimulates factors or materials that induce angiogenesis are promising
osteogenesis and forms a strong bond with host tissues . to be used in dual-delivery systems to induce angiogenesis
[7]
in combination with osteogenesis. Further factors or
BG has been combined with many different materials, materials are promising to be used in dual-delivery systems
for example, various hydrogels , graphene oxide , or to induce angiogenesis in combination with osteogenesis.
[8]
[9]
polycaprolactone , from which it is released and induces For example, PLGA was combined with various molecules,
[10]
osteogenic properties . By combining PLA and bioglass, for example, VEGF [24,25] .
[11]
it might be possible to combine the positive characteristics
One example besides PLA is the combination of PGLA
of these materials and overcome their negative aspects. with various bioactive molecules, for example, VEGF [24,25] .
Back in early 2000s, it was reported that the
combination of BG and PLA demonstrated positive It has been demonstrated in various studies that BG,
effects on bone regeneration [12-14] . The combination of as one part of composite materials, has positive effects on
[26]
both materials to form a printable composite is a new wound healing and angiogenesis. In combination with
research area and was reported firstly by Roether et al. collagen, BG induced vascularization of adipose tissue-
[14]
[27]
[28]
and Alksne et al. , who observed high cytocompatibility derived stem cells . Moreover, Deb et al. reported
[6]
and osteoinductive properties of the printed PLA–BG co-culture of human osteoblasts and endothelial cells
scaffolds. Another advantage of the combined material is on ceramic-BG scaffolds. Stähli et al. and Eldesoqi et al.
the degradation process. PLA has been shown to degrade observed a positive effect of BG released from composite
into acid products that might limit tissue regeneration. materials on endothelial cell morphogenesis [29,30] . A
However, the alkaline nature of BG reduces the acidic side positive effect has also been described for osteochondral
[31]
effects of these degradation products . regeneration .
[15]
We have recently manufactured a printable material Therefore, the aim of this study was to analyze the
consisting of PLA and increasing concentrations of S53P4 effects of the 3D-printed PLA–BG composite material on
Volume 9 Issue 5 (2023) 55 https://doi.org/10.18063/ijb.751