Three‐dimensional macroscopic scaffolds with a gradient in stiffness for functional regeneration of interfacial tissues

Abstract

A novel approach has been demonstrated to construct biocompatible, macroporous 3-D tissue engineering scaffolds containing a continuous macroscopic gradient in composition that yields a stiffness gradient along the axis of the scaffold. Polymeric microspheres, made of poly(D,L-lacticco-glycolic acid) (PLGA), and composite microspheres encapsulating a higher stiffness nanophase material (PLGA encapsulating CaCO 3 or TiO 2 nanoparticles) were used for the construction of microsphere-based scaffolds. Using controlled infusion of polymeric and composite microspheres, gradient scaffolds displaying an anisotropic macroscopic distribution of CaCO 3 / TiO 2 were fabricated via an ethanol sintering technique. The controllable mechanical characteristics and biocompatible nature of these scaffolds warrants further investigation for interfacial tissue engineering applications.

Osteogenic Differentiation of Human Bone Marrow Stromal Cells in Hydroxyapatite-Loaded Microsphere-Based Scaffolds

“…[18][19][20][21][22][23][24] Although microspheres have been used in tissue engineering for stratified designs, [25][26][27] the use of continuously graded microsphere-based scaffolds is still limited. 28,29 The combination of continuously graded microsphere-only scaffolds with mineral incorporation, which provides a continuous gradient in macroscopic material composition, has previously been demonstrated as a method, 30 but the long-term response of cells in this environment has not been investigated. To address osteoblastic cell response, the most logical step is to evaluate the 3-D performance of homogenous microsphere-based scaffolds with mineral incorporation before using a continuously-graded design, as in the current study.…”

“…The advantages of this approach relate to the ability to tightly control a gradient in physical or chemical properties across the length of the scaffold by using each single microsphere as a ''building block.'' The current study, for the first time, used a precision particle fabrication technology 28,[30][31][32] to make poly(d,l-lactic acid-co-glycolic acid) (PLGA) microspheres loaded with HAp nanoparticles. The microspheres were used to construct 3-D scaffolds with various HAp contents on which human bone marrow stromal cells (hBMSC) were osteogenically differentiated for 6 weeks.…”

Microsphere-Based Gradient Implants for Osteochondral Regeneration: a Long-Term Study in Sheep

“…Two different batches of monodisperse microspheres were prepared using the aforementioned emulsions of PLGA-CS-NaHCO 3 and PLGA-β-TCP according to our previously reported technology [12][13][14]. Briefly, uniform polymer droplets were created by introducing regular jet instabilities in the polymer stream through acoustic excitation via an ultrasonic transducer.…”

“…Microsphere-based gradient implants for osteochondral regeneration: a long-term study in sheep Research Article Fabrication of gradient scaffolds Gradient scaffolds were prepared using our previously reported technology [12][13][14][15]. Briefly, 50 mg of lyophilized chondrogenic microspheres and 100 mg of osteogenic microspheres were dispersed in DI water, and separately loaded into two syringes.…”

Designing gradient plotted scaffolds as a tool for improving osteochondral regeneration

“…Typically, bi-phasic or tri-phasic scaffolds have been developed, displaying either discrete or continuous gradients [76][77][78][79]. In order to define bi-or tri-phasic scaffolds different materials can be chosen.…”