Degradable RGD-Functionalized 3D-Printed Scaffold Promotes Osteogenesis

Abstract

To establish an ideal microenvironment for regenerating maxillofacial defects, recent research interests have concentrated on developing scaffolds with intricate configurations and manipulating the stiffness of extracellular matrix toward osteogenesis. Herein, we propose to infuse a degradable RGD-functionalized alginate matrix (RAM) with osteoid-like stiffness, as an artificial extracellular matrix, to a rigid 3D-printed hydroxyapatite scaffold for maxillofacial regeneration. The 3D-printed hydroxyapatite scaffold was produced by microextrusion technology and showed good dimensional stability with consistent microporous detail. RAM was crosslinked by calcium sulfate to manipulate the stiffness, and its degradation was accelerated by partial oxidation using sodium periodate. The results revealed that viability of bone marrow stem cells was significantly improved on the RAM and was promoted on the oxidized RAM. In addition, the migration and osteogenic differentiation of bone marrow stem cells were promoted on the RAM with osteoid-like stiffness, specifically on the oxidized RAM. The in vivo evidence revealed that nonoxidized RAM with osteoid-like stiffness upregulated osteogenic genes but prevented ingrowth of newly formed bone, leading to limited regeneration. Oxidized RAM with osteoid-like stiffness facilitated collagen synthesis, angiogenesis, and osteogenesis and induced robust bone formation, thereby significantly promoting maxillofacial regeneration. Overall, this study supported that in the stabilized microenvironment, oxidized RAM with osteoid-like stiffness offered requisite mechanical cues for osteogenesis and an appropriate degradation profile to facilitate bone formation. Combining the 3D-printed hydroxyapatite scaffold and oxidized RAM with osteoid-like stiffness may be an advantageous approach for maxillofacial regeneration.

3D-Printed Hydroxyapatite and Tricalcium Phosphates-Based Scaffolds for Alveolar Bone Regeneration in Animal Models: A Scoping Review

“…The included studies followed the Animal Research: Reporting of In Vivo Experiments (ARRIVE 2.0) guidelines for quality assessment in this review [ 36 ]. The 10 selected articles were published between 2016 and 2021 and were conducted in the USA (n = 4) [ 37 , 38 , 39 , 40 ], Taiwan (n = 2) [ 41 , 42 ], Korea (n = 2) [ 43 , 44 ], China (n = 1) [ 45 ] and Switzerland (n = 1) [ 46 ]. Table 1 and Table 2 summarize the details of the included studies using 3D HA-based and 3D TCP-based scaffolds.…”

“…Eight out of ten studies used large animal models, which were beagle dogs [ 43 , 44 , 46 ], canines [ 37 ] and rabbits [ 38 , 39 , 40 , 45 ], whereas the other two used small animal models, Sprague-Dawley rats, in their studies [ 41 , 42 ] ( Table 3 ). Tooth extraction of lower premolars and molars was carried out with a healing period of 6 to 12 weeks prior to defects’ preparation [ 37 , 43 , 46 ].…”

“…Tooth extraction of lower premolars and molars was carried out with a healing period of 6 to 12 weeks prior to defects’ preparation [ 37 , 43 , 46 ]. Eight studies involved surgically created defects on the mandible [ 37 , 38 , 41 , 42 , 43 , 44 , 45 , 46 ] and the remaining two studies were on the maxilla [ 39 , 40 ] to receive either 3D-printed HA-based or TCP-based bone scaffolds.…”

“…Three studies reported a combination of four interventions: 3D-printed HA and RGD-functionalized alginate matrix (RAM) as a supplement [ 42 ], 3D-printed HA with additional features of microchannels or macro-channels with or without a screw [ 37 ] and 3D-printed TCP and calcium silicate porous bioceramics [ 45 ]. Six studies were designed to have negative control groups, which were unfilled or untreated bone defects [ 38 , 39 , 40 , 41 , 42 , 43 ], and one positive control group [ 43 ]. Two studies reported the blinding of the treatment assignment to the surgical procedures [ 41 , 42 ].…”

“…Six studies were designed to have negative control groups, which were unfilled or untreated bone defects [ 38 , 39 , 40 , 41 , 42 , 43 ], and one positive control group [ 43 ]. Two studies reported the blinding of the treatment assignment to the surgical procedures [ 41 , 42 ].…”