Nano-ceramic Composite Scaffolds for Bioreactor-based Bone Engineering

Abstract

Background Composites of biodegradable polymers and bioactive ceramics are candidates for tissue-engineered scaffolds that closely match the properties of bone. We previously developed a porous, three-dimensional poly (D,L-lactide-co-glycolide) (PLAGA)/nanohydroxyapatite (n-HA) scaffold as a potential bone tissue engineering matrix suitable for high-aspect ratio vessel (HARV) bioreactor applications. However, the physical and cellular properties of this scaffold are unknown. The present study aims to evaluate the effect of n-HA in modulating PLAGA scaffold properties and human mesenchymal stem cell (HMSC) responses in a HARV bioreactor. Questions/purposes By comparing PLAGA/n-HA and PLAGA scaffolds, we asked whether incorporation of n-HA (1) accelerates scaffold degradation and compromises mechanical integrity; (2) promotes HMSC proliferation and differentiation; and (3) enhances HMSC mineralization when cultured in HARV bioreactors. Methods PLAGA/n-HA scaffolds (total number = 48) were loaded into HARV bioreactors for 6 weeks and monitored for mass, molecular weight, mechanical, and morphological changes. HMSCs were seeded on PLAGA/ n-HA scaffolds (total number = 38) and cultured in HARV bioreactors for 28 days. Cell migration, proliferation, osteogenic differentiation, and mineralization were characterized at four selected time points. The same amount of PLAGA scaffolds were used as controls.

Biomaterials for Bone Regenerative Engineering

“…The development of materials to activate specific genes and molecular tailoring of biomaterials to elicit desired cellular responses are some of the strategies utilized for development of third generation materials . Materials with appropriate physical characteristics such as high porosity and interconnectivity have been designed and engineered to facilitate material/cell interactions, nutrient/oxygen infiltration and vascularization . For example, Nukavarapu et al, developed optimally porous and mechanically compatible scaffolds for bone regenerative engineering .…”

“…Direct bone bonding was also realized by applying a hydroxyapatite coating on these metal implant surface . For synthetic polymers such as PLA, PLGA, and PCL, introduction of osteoconductivity into these materials were realized by either forming into composite with CaP ceramics or formation of CaP coating on their surfaces …”

“…For example, addition of hydroxyapatite into biodegradable polymers such as PLA, PLGA, and PCL led to the formation of composite materials possessing both excellent mechanical properties and bioactivity . More importantly, multiple studies have shown that incorporation of nano‐hydroxyapatite into porous 3D PLGA scaffolds substantially enhanced preosteoblast growth, differentiation and mineralization …”

Evaluation of PLAGA/n-HA Composite Scaffold Bioactivity in vitro

“…We hypothesized that incorporation of n-HA into the sintered PLAGA microsphere-based scaffolds could greatly improve the bioactivity of the scaffold. Previously, PLAGA/n-HA composite scaffolds have been successfully fabricated in our laboratory [19,20]. In this study, we focused on the evaluation of the bioactivity of these composite scaffolds compared to PLAGA scaffolds.…”

Regenerative Engineering: Approaches to Limb Regeneration and Other Grand Challenges

“…Similarly, the field of biomaterials science has significantly advanced from the level of biodegradable polymers and ceramics to custom designed biomimetic inductive biomaterials with carefully modulated physical, mechanical and biological properties to enhance the natural regenerative process of the body [9–11]. The emergence of micro and nanotechnologies fueled the developments in this area by lending new methodologies to create three dimensional biomimetic scaffolds [12,13]. The studies in this area so far enabled us to understand the cellular sensitivity towards the biological environment and therefore the potential to modulate the cellular functions using advanced biomaterials and biomimetic scaffolds.…”