Investigation of multiphasic 3D‐bioplotted scaffolds for site‐specific chondrogenic and osteogenic differentiation of human adipose‐derived stem cells for osteochondral tissue engineering applications

Abstract

Osteoarthritis is a degenerative joint disease that limits mobility of the affected joint due to the degradation of articular cartilage and subchondral bone. The limited regenerative capacity of cartilage presents significant challenges when attempting to repair or reverse the effects of cartilage degradation. Tissue engineered medical products are a promising alternative to treat osteochondral degeneration due to their potential to integrate into the patient's existing tissue. The goal of this study was to create a scaffold that would induce site-specific osteogenic and chondrogenic differentiation of human adipose-derived stem cells (hASC) to generate a full osteochondral implant. Scaffolds were fabricated using 3D-bioplotting of biodegradable polycraprolactone (PCL) with either β-tricalcium phosphate (TCP) or decellularized bovine cartilage extracellular matrix (dECM) to drive site-specific hASC osteogenesis and chondrogenesis, respectively. PCL-dECM scaffolds demonstrated elevated matrix deposition and organization in scaffolds seeded with hASC as well as a reduction in collagen I gene expression. 3D-bioplotted PCL scaffolds with 20% TCP demonstrated elevated calcium deposition, endogenous alkaline phosphatase activity, and osteopontin gene expression. Osteochondral scaffolds comprised of hASC-seeded 3D-bioplotted PCL-TCP, electrospun PCL, and 3D-bioplotted PCL-dECM phases were evaluated and demonstrated site-specific osteochondral tissue characteristics.This technique holds great promise as cartilage morbidity is minimized since autologous cartilage harvest is not required, tissue rejection is minimized via use of an abundant and accessible source of autologous stem cells, and biofabrication techniques allow for a precise, customizable methodology to rapidly produce the scaffold.Liliana F. Mellor and Rachel C. Nordberg contributed equally to this work.

Adipose-Derived Stem Cells: Current Applications and Future Directions in the Regeneration of Multiple Tissues

“…Osteoarthritis (OA) is a progressive degenerative joint disease characterized by the deterioration of articular cartilage and pathological changes in the adjacent subchondral bone [ 97 ]. Current conventional treatments (physical therapy, glucosamine, chondroitin sulfate supplementation, and arthroscopic surgery) or surgical therapies (abrasion arthroplasty, subchondral drilling, and microfracture) are aimed at alleviating pain and enhancing joint function; however, they are limited by their low efficacy [ 98 ], and intra-articular (IA) injection of ADSCs to repair damaged cartilage has potential as a suitable alternative.…”

Osteochondral Tissue Engineering: The Potential of Electrospinning and Additive Manufacturing

“…In spite of this, synthetic biomaterials have a very important shortcoming: their artificial and bioinert nature hinders cell recognition and attachment, due to the absence of natural ECM components that can guide these processes and enhance neotissue formation and organisation. This drawback has led to a growing number of studies focusing on the development of composites or blends containing both synthetic and naturally occurring elements so that the reproducibility and mechanical properties of artificial materials can be combined with cell-instructive ECM constituents [ 134 , 135 , 136 , 137 ].…”

“…As such, AM techniques have the immeasurable potential for precision medicine, since they enable mass customisation, generation of constructs with complex geometries, and the use of multiple biomaterials with variable physicochemical properties [ 326 ]. Depending on the specific AM methodology, natural [ 327 , 328 , 329 ] and/or synthetic [ 135 , 151 ] materials, as well as ceramics or metals [ 330 , 331 ], can be used in AM as resins or inks.…”

Artificial decellularized extracellular matrix improves the regenerative capacity of adipose tissue derived stem cells on 3D printed polycaprolactone scaffolds

“…4,5 However artificial tissue grafts created by means of tissue engineering and regenerative medicine can be a promising alternative. 6 The basic principle of manufacturing artificial, biologically activated replacement material Artificial decellularized extracellular matrix improves the regenerative capacity of adipose tissue derived stem cells on 3D printed polycaprolactone scaffolds is the combination of cells, growth factors, and biomaterials. 7 In order to achieve a physiological replacement, there are many requirements regarding features of applied biomaterials such as sufficient mechanical stability, shape maintenance, and degradability by the body.…”