Segmental bone replacement via patient‐specific, three‐dimensional printed bioresorbable graft substitutes and their use as templates for the culture of mesenchymal stem cells under mechanical stimulation at various frequencies

Abstract

The treatment of large segmental bone defects remains a challenge as infection, delayed union, and nonunion are common postoperative complications. A three-dimensional printed bioresorbable and physiologically load-sustaining graft substitute was developed to mimic native bone tissue for segmental bone repair. Fabricated from polylactic acid, this graft substitute is novel as it is readily customizable to accommodate the particular size and location of the segmental bone of the patient to be replaced. Inspired by the structure of the native bone tissue, the graft substitute exhibits a gradient in porosity and pore size in the radial direction and exhibit mechanical properties similar to those of the native bone tissue. The graft substitute can serve as a template for tissue constructs via seeding with stem cells. The biocompatibility of such templates was tested under in vitro conditions using a dynamic culture of human mesenchymal stem cells. The effects of the mechanical loading of cell-seeded templates under in vitro conditions were assessed via subjecting the tissue constructs to 28 days of daily mechanical stimulation. The frequency of loading was found to have a significant effect on the rate of mineralization, as the alkaline phosphatase activity and calcium deposition were determined to be particularly high at the typical walking frequency of 2 Hz, suggesting that mechanical stimulation plays a significant role in facilitating the healing process of bone defects. Utilization of such patient-specific and biocompatible graft substitutes, coupled with patient's bone marrow cells seeded and exposed to mechanical stimulation of 2 Hz have the potential of reducing significant volumes of cadaveric tissue required, improving long-term graft stability and incorporation, and alleviating financial burdens associated with delayed or failed fusions of long bone defects.

3D Bone Biomimetic Scaffolds for Basic and Translational Studies with Mesenchymal Stem Cells

“…Moving closer to the bedside, considering the need for patient-specific graft substitutes for segmental bone repair, Chung and colleagues fabricated 3D-printed PLLA templates with a gradient in porosity and pore size resembling the native tissue, good biocompatibility under dynamic culture of hMSCs, and responsiveness to a physiologically relevant mechanical loading [ 104 ]. Therefore, this graft substitute was deemed of interest for exploitation in critical-sized bone defect correction in patients.…”

Extra low interstitial titanium based fully porous morphological bone scaffolds manufactured using selective laser melting

“…The use of porous scaffolds as bone substitutes for large segmental bone defect is hindered by the limited vascularisation, bone ingrowth, stress shielding and maladapted stress concentration [15,40,55,68]. In a previous study, the possibility of anatomical scaffolds featuring a sheathed design was proposed for possible stiffness matching and to mimic the structure of the bone [7].…”

“…1 was extracted. The section length is purely arbitrary and is representative of cases where autologous bone graft may be considered [15,45]. This was considered in order to make sure that scaffold developed can be used for bone growth analysis using bioreactors in the future.…”

“…Beyond efficiency, the proposed morphologically matched porous methodology drastically minimises material mass at the same time preserving the bones natural loading pattern in comparison to traditional scaffolds [15].…”

Load‐bearing biodegradable polycaprolactone‐poly (lactic‐co‐glycolic acid)‐ beta tri‐calcium phosphate scaffolds for bone tissue regeneration

“…The use of various fabrication methods to generate gradients in porosity, bioactive concentrations, and mechanical properties in the axial and transverse directions has the potential to further optimize scaffold structures, mechanical properties, and bioactive concentrations for the treatment and repair of critical-sized bone defects. [40][41][42][43][44][45][46] Such methods can be tailored using the results of this investigation as to what the PCL/PLGA ratio needs to be at various radial and axial locations of the scaffolds and bone graft substitutes.…”