3D silicon doped hydroxyapatite scaffolds decorated with Elastin-like Recombinamers for bone regenerative medicine

Abstract

Abstract.The current study reports on the manufacturing by rapid prototyping technique of threedimensional (3D) scaffolds based on silicon substituted hydroxyapatite with Elastin-like Recombinamers (ELRs) functionalized surfaces. Silicon doped hydroxyapatite (Si-HA), with Ca 10 (PO 4 ) 5.7 (SiO 4 ) 0.3 (OH) 1.7 h 0.3 nominal formula, was surface functionalized with two different types of polymers designed by genetic engineering: ELR-RGD that contain cell attachment specific sequences and ELR-SN A 15/RGD with both hydroxyapatite and cells domains that interact with the inorganic phase and with the cells, respectively. These hybrid materials were subjected to in vitro assays in order to clarify if the ELRs coating improved the well-known biocompatible and bone regeneration properties of calcium phosphates materials. The in vitro tests shown that there was a total and homogeneous colonization of the 3D scaffolds by Bone marrow Mesenchymal Stromal Cells (BMSCs). In addition, the BMSCs were viable and able to proliferate and differentiate into osteoblasts. Statement of significanceBone tissue engineering is an area of increasing interest because its main applications are directly related to the rising life expectancy of the population, which promotes higher rates of several bone pathologies, so innovative strategies are needed for bone tissue regeneration therapies. Here we use the rapid prototyping technology to allow moulding ceramic 3D scaffolds and we use different bio-polymers for the functionalization of their surfaces in order to enhance the biological response.Combining the ceramic material (silicon doped hydroxyapatite, Si-HA) and the Elastinlike Recombinamers (ELRs) polymers with the presence of the integrin-mediate 3 adhesion domain alone or in combination with SN A 15 peptide that possess high affinity for hydroxyapatite, provided an improved Bone marrow Mesenchymal Stromal Cells (BMSCs) differentiation into osteoblastic linkage.

An elastin-like recombinamer-based bioactive hydrogel embedded with mesenchymal stromal cells as an injectable scaffold for osteochondral repair

“…As pointed out above, the ELRs show thermosensitivity, thus meaning that hydrogels, which are stable at body temperature, can be formed whenever the T t of the ELR is lower than this temperature [27]. Several studies have shown how different types of ELRs can be used in some of the most challenging fields of tissue regeneration, such as cardiovascular [28], ocular prosthesis [29] and osteochondral applications [30, 31], among others [27].…”

Genetically Engineered Elastin-based Biomaterials for Biomedical Applications

“…However, when osteoblast differentiation was evaluated, expression of the osteoblast markers OC and ALP demonstrated that the Si-HA-SNA15containing scaffolds were very efficient at leading the rBMSCs into the osteoblastic lineage. In summary, we can conclude that although cells were able to grow on and colonize any of the scaffolds tested, their behavior differed and the biochemical signal generated by the functionalized ELR significantly enhanced the osteoconductive properties of the scaffolds [115]. In contrast to bone, some tissues, such as enamel for example, are unable to regenerate.…”

RGD‐functionalized polyurethane scaffolds promote umbilical cord blood mesenchymal stem cell expansion and osteogenic differentiation

“…However, all cell‐validated attempts were limited to a maximum of 3‐mm total thickness (Chen et al, ; Choi et al, ; Rodda et al, ). A homogenous distribution of bone marrow MSCs on silicon‐substituted hydroxyapatite scaffolds functionalized with elastin‐like recombinamers‐RGD has been achieved, but only on a maximum 2‐mm scaffold thickness (Vila et al, ). Similarly, functionalized polyethylene glycol molecules with cyclic RGD on aerographite produced 3D scaffolds of 3‐mm thickness but did not achieve cellular infiltration further than a depth of 580 μm (Lamprecht et al, ).…”