Improving the permeability of lyophilized collagen–hydroxyapatite scaffolds for cell‐based bone regeneration with a gelatin porogen

Abstract

Bone tissue engineering using biomaterial scaffolds and culture-expanded osteoprogenitor cells has been demonstrated in several studies; however, it is not yet a clinical reality. One challenge is the optimal design of scaffolds for cell delivery and the identification of scaffold parameters that can delineate success and failure in vivo. Motivated by a previous experiment in which a batch of lyophilized collagen-hydroxyapatite (HA) scaffolds displayed modest bone formation in vivo, despite having large pores and high porosity, we began to investigate the effect of scaffold permeability on bone formation. Herein, we fabricated scaffolds with a permeability of 2.17 ± 1.63 × 10 m /(N s) and fourfold higher using a sacrificial gelatin porogen. Scaffolds were seeded with mouse bone marrow stromal cells carrying a fluorescent reporter for osteoblast differentiation and implanted into critical-size calvarial defects in immunodeficient mice. The porogen scaffold group containing a 1:1 ratio of solids to beads was significantly more radiopaque than the scaffold group without the bead porogen 3 weeks after implantation. Quantitative histomorphometry uncovered the same trend between the 1:1 group and scaffolds without porogen found in the radiographic data; however, this was not statistically significant here. Taken together, the X-ray and histology suggest that the 1:1 ratio of porogen to scaffold solids, resulting in a fourfold increase in permeability, may enhance bone formation when compared to scaffolds without porogen. Scaffold permeability can be a useful quality control measure before implantation and this practice should improve the consistency and efficacy of cell-based bone tissue engineering. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1580-1590, 2016.

Placenta Derived Mesenchymal Stem Cells Hosted on RKKP Glass-Ceramic: A Tissue Engineering Strategy for Bone Regenerative Medicine Applications

“…For this reason and due to the limited survival of stem cells suspended in a buffer, the engraftment rate may be improved by using a supporting matrix such as a scaffold or a hydrogel [18]. An ideal biomaterial scaffold for cell delivery supporting osteogenesis has not been yet identified [19], and current efforts are directed towards the design of a scaffold able to heal bone defects in specific anatomic sites and also favorably affect bone formation by stimulating osteoblastic cell proliferation and differentiation [20].…”

Biomineralization of Recombinant Peptide Scaffolds: Interplay among Chemistry, Architecture, and Mechanics

“…Scaffold architecture has been observed to play a major role in the final clinical outcome of scaffolds in vivo. 12,13 The need for a highly permeable structure, to maximize nutrient and cell infiltration, dictated that scaffolds with anisotropic, linear pores were manufactured. 25 There is a fine balance between an increased permeability, a result of larger pore sizes, and a reduction in the surface area available for cell attachment as the pore size increases.…”

“…9−11 In addition, high scaffold permeability to fluid flow has been shown to increase bone integration in vivo. 12,13 To capitalize on this, aligned lamellar structures were produced, which not only mimic the natural ECM organization of bone but also have been shown to have higher permeability than isotropic scaffolds. 1,14 Naturally, mechanical cues cannot be neglected, as they also direct osteogenesis and mineralization.…”

“…Scaffold structures must match certain key requirements to encourage cellular infiltration. These include pore sizes of 200–400 μm, with pore interconnections above 100 μm. − In addition, high scaffold permeability to fluid flow has been shown to increase bone integration in vivo . , To capitalize on this, aligned lamellar structures were produced, which not only mimic the natural ECM organization of bone but also have been shown to have higher permeability than isotropic scaffolds. , …”

Nanocellulose-collagen-apatite composite associated with osteogenic growth peptide for bone regeneration

“…Bioactive-polymeric materials have demonstrated to be potential candidates to improve the biological and mechanical properties in bone tissue engineering, mainly composites based on HA and collagen have shown good results of biological/mechanical properties and chemical stability [22,23]. Indeed, alloplastic materials containing HA and collagen are bone substitutes of choice due to their physicochemical features similar to bone tissue besides them can be effective and predictable materials in bone repair/regeneration [24,25].…”