Osteoinductive potential of small intestinal submucosa/ demineralized bone matrix as composite scaffolds for bone tissue engineering

Abstract

Background: Demineralized bone matrix (DBM) is extensively used in orthopedic, periodontal, and maxillofacial application and investigated as a material to induce new bone formation. Small intestinal submucosa (SIS) derived from the submucosa layer of porcine intestine has widely utilized as biomaterial with minimum immune response. Objectives: Determine the osteoinductive potential of SIS, DBM, SIS/DBM composites in the in vitro cell culture and in vivo animal bioassays for bone tissue engineering. Materials and methods: Human periosteal (HPO) cells were treated in the absence or presence SIS, DBM, and SIS/DBM. Cell proliferation was examined by direct cell counting. Osteoblast differentiation of the HPO cells was analyzed with alkaline phosphatase activity assay. The Wistar rat muscle implant model was used to evaluate the osteoinductive potential of SIS, DBM, and SIS/DBM composites. Results: HPO cells could differentiate along osteogenic lineage when treated with either DBM or SIS/DBM. SIS/ DBM had a tendency to promote more cellular proliferation and osteoblast differentiation than the other treatments. In Wistar rat bioassay, SIS showed no new bone formation and the implants were surrounded by fibrous tissues. DBM demonstrated new bone formation along the edge of old DBM particles. SIS/DBM composite exhibited high osteoinductivity, and the residual SIS/DBM was surrounded by osteoid-like matrix and newly formed bone. Conclusion: DBM and SIS/DBM composites could retain their osteoinductive capability. SIS/DBM scaffolds may provide an alternative approach for bone tissue engineering.

A novel gelatin/chitooligosaccharide/demineralized bone matrix composite scaffold and periosteum-derived mesenchymal stem cells for bone tissue engineering

“…Moreover, collagen scaffolds with incorporated DBM could enhance cell attachment, stimulate cell proliferation, and promote osteogenic differentiation [ 12 ]. Additionally, DBM combined with small intestinal submucosa composite exhibited superior osteoinductivity, provided a suitable environment for osteoblast differentiation, and ultimately enhanced new bone formation [ 25 ]. Our findings from this study are in accordance with reports from recent studies, although different scaffolds were used.…”

Advancing biomaterials of human origin for tissue engineering

“…In one study, although SIS without cell seeding resulted in no new bone formation in vivo , whereas DBM alone demonstrated new bone formation along the edge of old DBM particles, an SIS/DBM composite exhibited higher osteoinductivity. Moreover, the residual SIS/DBM was surrounded by an osteoid-like matrix and newly formed bone [527]. The capacity for localized collagen formation and osteocalcin deposition by SIS-ECM was demonstrated in a full-thickness bilateral bone-defect model in rat crania; the defects were managed with SIS sponges, and the presence of bone marrow-derived stem cells (BMSCs) resulted in significantly greater bone formation [528].…”

Leveraging “Raw Materials” as Building Blocks and Bioactive Signals in Regenerative Medicine

“…132,135 In addition to these native ECM molecules, the collagen fiber orientation that is maintained after the decell process has also attracted attention. 132 Both of these inherent properties have sparked strategies employing SIS as scaffolds in the fields of cardiovascular, [137][138][139][140] bone, [141][142][143] nerve, 144 soft tissue, 86,87,145 and urogenital [146][147][148][149] tissue engineering (Table 6). Currently, SIS is Food and Drug Administration (FDA) approved for several urogenital applications, including hernia repair.…”

“…132 The presence of aligned collagen fibers and endogenous growth factors remaining in the acellular SIS matrix has sparked interest within the bone tissue engineering community as well. Kim et al 142 and Honsawek et al 141 showed that SIS scaffolds promoted new bone formation in a rat model. Zhao et al 143 found similar results in a rabbit model when SIS was seeded with MSCs.…”

“…Researchers have used DBM as a sole scaffold component in conjunction with seeded umbilical cord blood-derived MSCs 152 and adiposederived stem cells. 154,155 Combination of DBM with additional raw materials, such as SIS, 141 HAp, 156 and b-TCP, 157 as well as fibrin glue 158,159 and heparin, 153 has been employed in bone and cartilage tissue engineering. In addition, blends of DBM with synthetic PLA, 160 reverse thermoresponsive polymers, 161 and PLGA 162 allow for increased stability and modulation of mechanical properties.…”