Bone augmentation after ectopic implantation of a cell-free collagen-hydroxyapatite scaffold in the mouse

Abstract

The bone grafting is the classical way to treat large bone defects. Among the available techniques, autologous bone grafting is still the most used but, however, it can cause complications such as infection and donor site morbidity. Alternative and innovative methods rely on the development of biomaterials mimicking the structure and properties of natural bone. In this study, we characterized a cell-free scaffold, which was subcutaneously implanted in mice and then analyzed both in vivo and ex vivo after 1, 2, 4, 8 and 16 weeks, respectively. Two types of biomaterials, made of either collagen alone or collagen plus magnesium-enriched hydroxyapatite have been used. The results indicate that bone augmentation and angiogenesis could spontaneously occur into the biomaterial, probably by the recruitment of host cells, and that the composition of the scaffolds is crucial. In particular, the biomaterial more closely mimicking the native bone drives the process of bone augmentation more efficiently. Gene expression analysis and immunohistochemistry demonstrate the expression of typical markers of osteogenesis by the host cells populating the scaffold. Our data suggest that this biomaterial could represent a promising tool for the reconstruction of large bone defects, without using exogenous living cells or growth factors.

Innovative Biomaterials for Tissue Engineering

“…Calabrese et al in their studies tested a composite bi-layer type-1 collagen-HA/Mg scaffold for osteochondral regeneration, both in vitro and in vivo. They showed that the combination of this scaffold with mesenchymal stem cells (MSC) derived from adipose tissue (hAD-SCs) in the presence of specific differentiation conditions induce osteochondro differentiation both in vitro and in vivo [19][20][21][22][23].…”

“…Also, our group tested in vitro and in vivo potential of collagen type-1/Ha-Mg combination to promote bone injury healing. We demonstrated that although biomimetic scaffolds are "per sè" able to promote tissue regeneration thanks to their high osteoinductivity, their combination with progenitor cells and growth factors would be more efficient [19][20][21]. Generally, osteogenic cells such as adult stem cells (ASC) isolated from adult tissues like bone marrow, adipose tissue, or muscle are good candidate to be transplanted in skeletal lesion together with an appropriate scaffold.…”

In vivo Evaluation of a Collagen Scaffold Preconditioned with Adipose-derived Mesenchymal Stem Cells Used for Bone Regeneration A histological study

“…The noncollagenous proteins form only 10% of the bone mass. [13] The glycoproteins are represented by alkaline phosphatase, bone sialoprotein, osteopontin and osteocalcin (which modulate the mineralization process) and osteonectin (determines the diameter of collagen fibrils) [14,15]. The proteoglycans are up to 10% of the non-collagenous proteins and offer resistance to compressive forces; they also have the capacity to bond to growth factors that can be stored in bone extracellular matrix for future use [7].…”

Vegetable hierarchical structures as template for bone regeneration: New bio‐ceramization process for the development of a bone scaffold applied to an experimental sheep model

“…A similar approach was carried out in the last decade to reproduce the spongy bone part (Sprio, Panseri, Cunha, & Tampieri, 2012;Tampieri, Sprio, Sandri, & Valentini, 2011). Hybrid porous scaffolds were obtained by a biomineralization process, that is, heterogeneous nucleation of hydroxyapatite on collagen matrix, that resulted in high regenerative ability in several preclinical and clinical studies (Calabrese et al, 2016;Kon et al, 2010;Minardi et al, 2015;Torres-Raya et al, 2008). In this light the scaffold of this study was designed as a bi-layer device associating: (a) BioSiC, developed as a mechanically-resistant porous shell, and presenting a hierarchic structure translated from the original wood template with (b) a soft, highly bioactive scaffold obtained by biomineralization, presenting bone-mimicking phase and atomic composition (i.e., the inorganic phase was Mg-and CO 3 -co-substituted hydroxyapatite [Mg-CHA] (Sprio et al, 2012;Tampieri et al, 2003)), and character- growth factors in osteoconductive matrix) is well accepted, and promising results have been already shown (Filardo et al, 2014).…”