Three-dimensional printed polylactic acid scaffold integrated with BMP-2 laden hydrogel for precise bone regeneration

Shi Huan Han,Misun Cha,Yuan-Zhe Jin,Jae Hyup Lee,Byung Sun Choi,Jin Wook Park,Kyung Mee Lee

doi:10.1186/s40824-021-00233-7

Shi Huan Han, Misun Cha + Show 5 more

Open Access

https://doi.org/10.1186/s40824-021-00233-7

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Abstract

BackgroundCritical bone defects remain challenges for clinicians, which cannot heal spontaneously and require medical intervention. Following the development of three-dimensional (3D) printing technology is widely used in bone tissue engineering for its outstanding customizability. The 3D printed scaffolds were usually accompanied with growth factors, such as bone morphometric protein 2 (BMP-2), whose effects have been widely investigated on bone regeneration. We previously fabricated and investigated the effect of a polylactic acid (PLA) cage/Biogel scaffold as a carrier of BMP-2. In this study, we furtherly investigated the effect of another shape of PLA cage/Biogel scaffold as a carrier of BMP-2 in a rat calvaria defect model and an ectopic ossification (EO) model.MethodThe PLA scaffold was printed with a basic commercial 3D printer, and the PLA scaffold was combined with gelatin and alginate-based Biogel and BMP-2 to induce bone regeneration. The experimental groups were divided into PLA scaffold, PLA scaffold with Biogel, PLA scaffold filled with BMP-2, and PLA scaffold with Biogel and BMP-2 and were tested both in vitro and in vivo. One-way ANOVA with Bonferroni post-hoc analysis was used to determine whether statistically significant difference exists between groups.ResultThe in vitro results showed the cage/Biogel scaffold released BMP-2 with an initial burst release and followed by a sustained slow-release pattern. The released BMP-2 maintained its osteoinductivity for at least 14 days. The in vivo results showed the cage/Biogel/BMP-2 group had the highest bone regeneration in the rat calvarial defect model and EO model. Especially, the bone regenerated more regularly in the EO model at the implanted sites, which indicated the cage/Biogel had an outstanding ability to control the shape of regenerated bone.ConclusionIn conclusion, the 3D printed PLA cage/Biogel scaffold system was proved to be a proper carrier for BMP-2 that induced significant bone regeneration and induced bone formation following the designed shape.

Highlights

The critical bone defects that cannot heal spontaneously remain a major challenge for clinicians
Characterization of cage for drug delivery The hollow cavity of the cage was confirmed by the injection of blue ink mixed Biogel and the maximum loading capacity of the polylactic acid (PLA) cage was 35 μL. (Fig. 2a) The structural morphology of cage scaffold infilled with Biogel was characterized by scanning electron microscopy (SEM) after sputter coating the samples with Pt (Fig. 2b)
FT-IR spectroscopy results showed the characteristic absorption bands of its polysaccharide structure [15], which indicated the Biogel was composed of alginate and gelatin.(Fig. 2c) The hydroxyl (−OH), amino (−NH2) groups of gelatin stretching bands appeared in the FT-IR spectrogram

Summary

Result

The in vitro results showed the cage/Biogel scaffold released BMP-2 with an initial burst release and followed by a sustained slow-release pattern. The released BMP-2 maintained its osteoinductivity for at least 14 days. The in vivo results showed the cage/Biogel/BMP-2 group had the highest bone regeneration in the rat calvarial defect model and EO model. The bone regenerated more regularly in the EO model at the implanted sites, which indicated the cage/Biogel had an outstanding ability to control the shape of regenerated bone

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