The Emerging Use of ASC/Scaffold Composites for the Regeneration of Osteochondral Defects

Abstract

Articular cartilage is composed of chondrocytes surrounded by a porous permeable extracellular matrix. It has a limited spontaneous healing capability post-injury which, if left untreated, can result in severe osteochondral disease. Currently, osteochondral (OC) defects are treated by bone marrow stimulation, artificial joint replacement, or transplantation of bone, cartilage, and periosteum, while autologous osteochondral transplantation is also an option; it carries the risk of donor site damage and is limited only to the treatment of small defects. Allografts may be used for larger defects; however, they have the potential to elicit an immune response. A possible alternative solution to treat osteochondral diseases involves the use of stromal/stem cells. Human adipose-derived stromal/stem cells (ASCs) can differentiate into cartilage and bone cells. The ASC can be combined with both natural and synthetic scaffolds to support cell delivery, growth, proliferation, migration, and differentiation. Combinations of both types of scaffolds along with ASCs and/or growth factors have shown promising results for the treatment of OC defects based on in vitro and in vivo experiments. Indeed, these findings have translated to several active clinical trials testing the use of ASC-scaffold composites on human subjects. The current review critically examines the literature describing ASC-scaffold composites as a potential alternative to conventional therapies for OC tissue regeneration.

Adipose-derived stem cell-based optimization strategies for musculoskeletal regeneration: recent advances and perspectives

“…In musculoskeletal tissue engineering, scaffold materials include organic and inorganic sources, such as natural polymers (e.g., fibrin, hyaluronic acid, chitosan, collagen, alginate, and silk fibroin), inorganic materials (e.g., hydroxyapatite, tricalcium phosphate, glass ceramics, and titanium), and synthetic biodegradable polymers [e.g., polycaprolactone, polylactic acid (PLA), polyglycolic acid, and polylactic-co-glycolic acid (PLGA)] [ 58 , 59 ]. Novel synthetic scaffolds can be fabricated from different biomaterials, such as natural and synthetic polymers or inorganic ceramics and polymers, thereby eliminating the disadvantages of conventional scaffolds while enhancing their properties, including mechanical strength, porosity, wettability, angiogenic potential, and cell-material interactions required for tissue regeneration [ 60 , 61 ].…”

“…The combination of ADSCs with novel biomaterials or matrix proteins is being investigated as potential optimization strategies for cartilage regeneration. Biomaterials and matrix proteins can create a niche microenvironment that enhances the delivery, migration, proliferation, and differentiation of ADSCs [ 59 ]. As natural polymers, hyaluronic acid combined with allogeneic ADSCs efficiently promoted cartilage regeneration and prevented osteoarthritis progression in sheep [ 116 , 117 ].…”

Adipose-Derived Mesenchymal Stromal Cells: A Tool for Bone and Cartilage Repair

“…Depending on the anatomical region from which the adipose sample is taken, some differences have been reported. For example, a greater number of cells can be isolated from the adipose tissue of the arm, whereas cells with excellent plasticity can be obtained from the groin area [20]. Many studies have been carried out on adipose tissue contained in the lipoaspirate that is available after liposuction and would be otherwise discarded.…”

“…It is important to underline that ASCs have a low immunological reactivity, thanks to the absence or low expression of immunogenic surface antigens (CD40, CD40L, CD80 and CD86) and major histocompatibility complex II. This low immunological reactivity also makes them suitable for allogeneic use [20]. In addition, ASCs are able to modulate T and B cell activity and exert anti-inflammatory effects [36].…”

“…On the other hand, many more nonmetallic scaffolds have been designed, each of them characterized by different advantages and disadvantages. Examples of these scaffolds include the acellular matrix, coralline scaffolds, natural or synthetic polymers and hybrid scaffolds [20,58,59]. Ideal scaffolds should be degradable and biocompatible and mimic as closely as possible the physiological microenvironment of the target tissue.…”