Bone regeneration response in an experimental long bone defect orthotopically implanted with alginate‐pullulan‐glass‐ceramic composite scaffolds

Abstract

In the present study, scaffolds based on alginate‐pullulan‐bioactive glass‐ceramic with 0.5 and 1.5 mol % copper oxide were orthotopically implanted in experimental rat models to assess their ability to heal an induced bone defect. By implying magnetic resonance and imaging scans together with histological evaluation of the processed samples, a progressive healing of bone was observed within 5 weeks. Furthermore, as the regenerative process continued, new bone tissue was formed, enhancing the growth of irregular bone spicules around the scaffolds. A significantly higher amount of new bone was formed (37%) in the defect that received the composite with 1.5 mol % CuO (in glass‐ceramic matrix) content implant. Nevertheless, the bone regeneration obtained by scaffold with 0.5 mol % CuO implanted is comparable with the alginate‐pullulan‐β‐tricalcium phosphate/hydroxiapatite composite implant. The assessed amount of new bone formed was found to be between 29.75 and 37.15% for all the composition involved in the present study. During this process a regeneration process was shown when the alginate‐pullulan composite materials were involved, fact that indicate the great potential of these materials to be used in tissue engineering.

Recent Advances of Pullulan and/or Dextran-Based Materials for Bone Tissue Engineering Strategies in Preclinical Studies: A Systematic Review

“…No additional study was added for selection after manually screening the list of references of selected publications. Finally, 28 studies were included for this systematic review: 16 used dextran-derived biomaterials ( Lafont et al, 2004 ; Maire et al, 2005a ; Chen et al, 2005 ; Chen et al, 2006 ; Chen et al, 2007 ; Degat et al, 2009 ; Abbah et al, 2012 ; Bölgen et al, 2014 ; Ritz et al, 2018 ; Chen et al, 2019 ; Ding et al, 2019 ; Fang et al, 2019 ) for bone regeneration, six used pullulan-derived biomaterials ( Hayashi et al, 2009 ; Fujioka-Kobayashi et al, 2012 ; Miyahara et al, 2012 ; Takahata et al, 2015 ; Charoenlarp et al, 2018 ; Popescu et al, 2020 ) and six used a combination of these two polysaccharides ( Fricain et al, 2013 ; Fricain et al, 2018 ; Schlaubitz et al, 2014 ; Frasca et al, 2017 ; Ribot et al, 2017 ) ( Table 1 ). A flowchart of the selection and inclusion process, based on PRISMA recommendations is presented in Figure 1 .…”

“…Ectopic bone formation was investigated in six studies using subcutaneous implantation in the back of animals or by muscular implantation (e.g., leg muscles) ( Table 2 ) ( Maire et al, 2005a ; Degat et al, 2009 ; Hayashi et al, 2009 ; Fricain et al, 2013 ; Chen et al, 2019 ; Yu et al, 2020 ). Orthotopic implantations were mainly performed on maxillofacial defects and long bone defects ( Tables 3 , 4 , 5 ) ( Lafont et al, 2004 ; Chen et al, 2005 ; Chen et al, 2006 ; Chen et al, 2007 ; Hayashi et al, 2009 ; Abbah et al, 2012 ; Fujioka-Kobayashi et al, 2012 ; Miyahara et al, 2012 ; Fricain et al, 2013 ; Bölgen et al, 2014 ; Schlaubitz et al, 2014 ; Takahata et al, 2015 ; Togami et al, 2015 ; Frasca et al, 2017 ; Ribot et al, 2017 ; Charoenlarp et al, 2018 ; Fricain et al, 2018 ; Ritz et al, 2018 ; Ding et al, 2019 ; Fang et al, 2019 ; Popescu et al, 2020 ; Shoji et al, 2020 ; Maurel et al, 2021 ; Wang et al, 2021 ). Nine studies investigated calvarial defects, six studies focused on mandibular or maxillary defects (e.g., periodontal, sinus bone augmentation), whereas 10 studies were performed on femoral defects (e.g., condyle, epiphysis, metaphysis), one study on ulnar defect and one study on tibial defect.…”

“…Among the 28 studies included, 24 used either dextran or pullulan as the main component for biomaterial design ( Lafont et al, 2004 ; Chen et al, 2005 ; Maire et al, 2005a ; Chen et al, 2006 ; Chen et al, 2007 ; Degat et al, 2009 ; Hayashi et al, 2009 ; Abbah et al, 2012 ; Fujioka-Kobayashi et al, 2012 ; Miyahara et al, 2012 ; Bölgen et al, 2014 ; Takahata et al, 2015 ; Charoenlarp et al, 2018 ; Ritz et al, 2018 ; Chen et al, 2019 ; Ding et al, 2019 ; Fang et al, 2019 ; Popescu et al, 2020 ) and six used a combination of these two polysaccharides ( Fricain et al, 2013 ; Schlaubitz et al, 2014 ; Frasca et al, 2017 ; Ribot et al, 2017 ; Fricain et al, 2018 ) ( Table 1 ). In most cases, when pullulan or dextran was used alone, chemical functionalization of the polysaccharide was performed to improve the cross-linking process and/or to promote their binding capacity to growth factors.…”

“…To induce or enhance bone formation, various elements were directly added in these scaffolds to generate composite scaffolds ( Figure 5 ). Bioceramics, such as hydroxyapatite (HA) ( Fricain et al, 2013 ; Schlaubitz et al, 2014 ; Ribot et al, 2017 ; Fricain et al, 2018 ; Ding et al, 2019 ; Fang et al, 2019 ; Maurel et al, 2021 ; Wang et al, 2021 ), β-tricalcium phosphate ( Takahata et al, 2015 ) (β-TCP) or bioactive glass ( Popescu et al, 2020 ) were thus added to the scaffolds in nine studies, whereas another natural or synthetic polymer was combined to the scaffold in nine studies ( Chen et al, 2005 ; Chen et al, 2006 ; Chen et al, 2007 ; Abbah et al, 2012 ; Togami et al, 2015 ; Ding et al, 2019 ; Fang et al, 2019 ; Popescu et al, 2020 ; Wang et al, 2021 ).…”

Engineering Polysaccharides for Tissue Repair and Regeneration

“…The scaffold could promote the growth of irregular bone needles around the scaffold and significantly promote bone regeneration. [ 184 ] Lima et al. used photopolymerization method to prepare methyl acrylic bone drug dextran (dextran–MA) and g‐cyclodextrin (g‐CD) microspheres with bionic super hydrophobic surface.…”