Integration of Stem Cell to Chondrocyte-Derived Cartilage Matrix in Healthy and Osteoarthritic States in the Presence of Hydroxyapatite Nanoparticles

Abstract

We investigated the effectiveness of integrating tissue engineered cartilage derived from human bone marrow derived stem cells (HBMSCs) to healthy as well as osteoarthritic cartilage mimics using hydroxyapatite (HA) nanoparticles immersed within a hydrogel substrate. Healthy and diseased engineered cartilage from human chondrocytes (cultured in agar gels) were integrated with human bone marrow stem cell (HBMSC)-derived cartilaginous engineered matrix with and without HA, and evaluated after 28 days of growth. HBMSCs were seeded within photopolymerizable poly (ethylene glycol) diacrylate (PEGDA) hydrogels. In addition, we also conducted a preliminary in vivo evaluation of cartilage repair in rabbit knee chondral defects treated with subchondral bone microfracture and cell-free PEGDA with and without HA. Under in vitro conditions, the interfacial shear strength between tissue engineered cartilage derived from HBMSCs and osteoarthritic chondrocytes was significantly higher (p < 0.05) when HA nanoparticles were incorporated within the HBMSC culture system. Histological evidence confirmed a distinct spatial transition zone, rich in calcium phosphate deposits. Assessment of explanted rabbit knees by histology demonstrated that cellularity within the repair tissues that had filled the defects were of significantly higher number (p < 0.05) when HA was used. HA nanoparticles play an important role in treating chondral defects when osteoarthritis is a co-morbidity. We speculate that the calcified layer formation at the interface in the osteoarthritic environment in the presence of HA is likely to have attributed to higher interfacial strength found in vitro. From an in vivo standpoint, the presence of HA promoted cellularity in the tissues that subsequently filled the chondral defects. This higher presence of cells can be considered important in the context of accelerating long-term cartilage remodeling. We conclude that HA nanoparticles play an important role in engineered to native cartilage integration and cellular processes.

The influence of tissue microenvironment on stem cell–based cartilage repair

“…This close similarity to glycosaminoglycans may account for the success that has been attributed to the use of alginate and agarose in cartilage defect repair applications. In addition, hydrogels exhibit high biocompatibility with cartilage stem cells, low cytotoxicity, and do not undergo hydrolysis through ester bonds. Although they usually take longer to degrade than hydrolysis polymers (e.g., PLGA), they are suitable for cartilage, a slow regeneration tissue .…”

Effects of PLGA Nanofibre on Osteoarthritic Chondrocytes

“…Tissue engineering of articular cartilage involves the process of articular chondrocytes isolation, followed by cell seeding on biocompatible matrices or scaffold, cell cultures and subsequent implantation of injured knees (Langer & Vacanti 1993). Various scaffolds have been successfully developed using natural or synthetic polymers and extensively studied in vitro and in vivo for cartilage tissue engineering (Dimida et al 2017;Dua et al 2016;Khorsand-Ghayeni et al 2016;Wang et al 2017). Important aspects such as the function, structure and organization need to be emphasized while constructing the scaffold for therapeutic applications.…”

“…Cell sources are an important factor in tissue engineering. To date, the usage of bone marrow mesenchymal stem cells (BMSCs) are extensively tested to develop treatment for cartilage injuries (Dua et al 2016;Nazempour & Van Wie 2016). Various studies have reported that BMSCs potentially support the regeneration of injured cartilage (Pak et al 2016;Ude et al 2018).…”

Synthesis and characterization of a cartilage model using hydroxyapatite, chitosan and polycaprolactone

“…La mayor parte de estos ensayos se han realizado sobre cartílago rotuliano, pues la patología articular es más frecuente a este nivel. Sin embargo, pese a los esfuerzos realizados hasta la fecha, la solución ideal aún parece lejos de llegar a la realidad clínica (13). Se han ensayado diversas matrices biodegradables con la finalidad de ser implantadas en la zona del defecto y favorecer el proceso de reparación condral (14,15).…”

“…En este contexto, actualmente han cobrado gran importancia los hidrogeles inyectables, especialmente los que incorporan nanopartículas de hidroxiapatita (nHA), pues potencian la integración del constructo condral a la matriz ósea (16,17). En este sentido, el papel de la hidroxiapatita parece fundamental, hasta tal punto que algunos autores han propuesto utilizarla incluso para favorecer la integración cartílago-cartílago (en contenidos inferiores al 1%) (13,17).…”