Bone regeneration in minipigs by intrafibrillarly-mineralized collagen loaded with autologous periodontal ligament stem cells

Abstract

Biomimetic intrafibrillarly-mineralized collagen (IMC) is a promising scaffold for bone regeneration because of its structural and functional similarity to natural bone. The objective of this study was to evaluate the bone regeneration potential of IMC loaded with autologous periodontal ligament stem cells (PDLSCs) in large bone defects in minipigs. A macroporous IMC with a bone-like subfibrillar nanostructure was fabricated using a biomimetic bottom-up approach. Non-healing full thickness defects were established on the cranial bone in minipigs, and IMC and hydroxyapatite (HA) scaffolds seeded with autologous PDLSCs were implanted into these defects. Computed tomographic imaging, histology staining, and atomic force microscopy were applied to evaluate to the quantity, micro/nano structures, and mechanical performance of the neo-bone after 12 weeks of implantation. Compared with HA, IMC showed superior regeneration properties characterized by the profuse deposition of new bony structures with a normal architecture and vascularization. Immunohistochemistry showed that the runt-related transcription factor 2 and transcription factor Osterix were highly expressed in the neo-bone formed by IMC. Furthermore, the nanostructure and nanomechanics of the neo-bone formed by IMC were similar to that of natural bone. This study provides strong evidence for the future clinical applications of the IMC-based bone grafts.

A novel role in skeletal segment regeneration of extracellular vesicles released from periodontal-ligament stem cells

“…8,9 Moreover, hPDLSCs have shown the ability to promote the bone-regenerative process in association with different scaffolds. 10,11 In addition, hPDLSCs exert immunomodulatory 12 and therapeutic effects, which may be mediated at least in part through the release of extracellular vesicles (EVs) that act as paracrine signalers. 13 Exosomes are small well-defined vesicles, ie, phospholipidic membrane-enclosed entities containing cytokines, proteins, lipids, and nucleic acids, such as mRNA and microRNAs.…”

Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds

“…Periodontal ligament is another important component of dental tissue that connects the cement found in the root region of a tooth to alveolar bone and is the best source of periodontal ligament stem cells (PDLSCs). PDLSCs are studied extensively for their differentiation properties in bone-tissue engineering [ 33 , 34 , 35 ].…”

“…The biomaterials used for scaffold preparation are natural biopolymers, synthetic polymers, ceramics and composites [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. Natural biopolymers include chitosan [ 28 , 60 , 61 , 62 , 63 ], alginate [ 46 , 64 , 65 ], cellulose [ 66 , 67 , 68 ], collagen [ 33 , 35 , 69 ], hyaluronan [ 70 , 71 , 72 ], fibrin [ 73 , 74 , 75 , 76 ] and silk [ 77 , 78 ]. The most commonly used synthetic polymers for scaffold preparation include poly (L-lactic acid) (PLA) [ 79 , 80 ], poly(lactic-co-glycolic acid) (PLGA) [ 81 , 82 , 83 , 84 ], polycaprolactone (PCL) [ 80 , 85 , 86 ], and poly(propylene fumarate) (PPF) [ 87 , 88 ].…”

“…A few natural polymers such as chitosan, collagen, cellulose, alginate and fibrin have also been explored for their potential in dental-tissue engineering, among which the collagen scaffold is the most popular [ 33 , 35 , 69 , 103 ]. Cross-linked collagen type-I scaffolds have been studied with DPSCs and it has been shown that these scaffolds were able to induce cellular differentiation and abundant calcification of the developed extracellular matrix in an in vitro environment [ 31 ].…”

Zein/gelatin/nanohydroxyapatite nanofibrous scaffolds are biocompatible and promote osteogenic differentiation of human periodontal ligament stem cells

“…4 hPDLSCs have become a hotspot in periodontal tissue engineering because of their ease of access, low immunogenicity, multi-directional differentiation ability, and cementum-periodontal ligament complex formation. [5][6][7][8] However, only a few studies have been reported on biomaterials with osteoinductive abilities for hPDLSCs. Therefore, it is urgent to develop biomaterials that facilitate the cytocompatibility and osteogenic differentiation of hPDLSCs.…”