Evaluation of multi-scale mineralized collagen–polycaprolactone composites for bone tissue engineering

Abstract

A particular challenge in biomaterial development for treating orthopedic injuries stems from the need to balance bioactive design criteria with the mechanical and geometric constraints governed by the physiological wound environment. Such trade-offs are of particular importance in large craniofacial bone defects which arise from both acute trauma and chronic conditions. Ongoing efforts in our laboratory have demonstrated a mineralized collagen biomaterial that can promote human mesenchymal stem cell osteogenesis in the absence of osteogenic media but that possesses suboptimal mechanical properties in regards to use in loaded wound sites. Here we demonstrate a multi-scale composite consisting of a highly bioactive mineralized collagen-glycosaminoglycan scaffold with micron-scale porosity and a polycaprolactone support frame (PCL) with millimeter-scale porosity. Fabrication of the composite was performed by impregnating the PCL support frame with the mineral scaffold precursor suspension prior to lyophilization. Here we evaluate the mechanical properties, permeability, and bioactivity of the resulting composite. Results indicated that the PCL support frame dominates the bulk mechanical response of the composite resulting in a 6000-fold increase in modulus compared to the mineral scaffold alone. Similarly, the incorporation of the mineral scaffold matrix into the composite resulted in a higher specific surface area compared to the PCL frame alone. The increased specific surface area in the collagen-PCL composite promoted increased initial attachment of porcine adipose derived stem cells versus the PCL construct.

Modifying the strength and strain concentration profile within collagen scaffolds using customizable arrays of poly-lactic acid fibers

“…We have previously shown that while hydrated CG scaffolds show reduced elastic moduli than non-hydrated scaffolds, the hydrated and dry scaffolds all show characteristic stress-strain behavior characteristic of low-density, open-cell foams (Caliari et al, 2015b; Caliari et al, 2014; Harley et al, 2007; Weisgerber et al, 2013a). Further, we have shown that composites formed from collagen scaffolds and polycaprolactone (PCL) support frame show identical mechanical performance in the dry and hydrated state due to the presence of the PCL phase (Weisgerber et al, 2016). While we do not expect significant short-term changes in the mechanical performance of the PLA-collagen composite due to the slow hydrolytic degradation of PLA, the ability to separately tailor the degradation characteristics of the CG scaffold via chemical crosslinking across a wide range (<2wks to >2 years) of half-lives (Harley et al, 2004) suggests future efforts to match PLA and collagen degradation rates with new tissue formation.…”

Mineralized collagen artificial bone repair material products used for fusing the podarthral joints with internal fixation—a case report

“…With special attention to risk factors and their connection to the principles of prevention and treatment, surgeons care more and more about the major long-term complications, reliable and safe implant, rhythm of resorbability and measures implemented in practice to minimize the sequelae [8, 9]. As a result of these concerns, biomaterials of choice entail attributes of excellent osteoconductivity, biocompatibility and additional properties like radiolucency, antibiosis, free of immunologic rejection, poor thermal conductivity and ability to induce osteanagenesis [10]. Fracture, non-union, collapse, subluxation and any other joint injury requiring reparative regeneration of osseous tissues indicate application of mineralized collagen artificial bone repair material products that are endued with all the merit of an ideal biomaterial.…”

“…With crystallized hydroxyapatite arrayed along fibrils of type I collagen, mineralized collagen fabricates the understructure of the hardest human connective tissues such as bone and dentin [10, 11]. Within the mineralized collagen, hydroxyapatite crystals with size on nanometer scale orderly juxtapose along fibrils fabricated from type I collagen in a specific hierarchically staggered nanostructure.…”

Anisotropic mineralized collagen scaffolds accelerate osteogenic response in a glycosaminoglycan-dependent fashion

“…Mineralized collagen scaffolds were fabricated using previously described procedures 10,11,21,27,[40][41][42][43][44][45] . In a cooled, jacketed vessel, 1.9 w/v% type I bovine collagen (Sigma-Aldrich, Missouri, USA), 0.84 w/v% chondroitin-6-sulfate (Sigma-Aldrich), and Ca(OH)2, H3PO4, and Ca(NO3)2·4H2O were thoroughly homogenized, making sure to prevent collagen clumping.…”

“…Sectioned scaffolds were placed onto glass slides and stained with an aniline blue solution (Thermo Fisher Scientific, Massachusetts, USA) to stain collagen fibers. Slides were then imaged with a NanoZoomer Digital Pathology System (Hamamatsu, Japan) and pore structure was analyzed with a custom Matlab pore size code to acquire an average pore size and pore aspect ratio for each scaffold 30,41 .…”