Tissue-Engineered Cartilage: The Crossroads of Biomaterials, Cells and Stimulating Factors

Abstract

Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering.

HIF-1α as a Regulator of BMP2-Induced Chondrogenic Differentiation, Osteogenic Differentiation, and Endochondral Ossification in Stem Cells

“…In addition, the application of transplantation techniques, such as osteochondral autologous transplantation and autologous chondrocyte implantation, are limited by insufficient amounts of healthy non-weight-bearing joint cartilage, donor site morbidity, loss of chondrocytic phenotypes during expansion, and immunological reactions [2,3]. As a result, the use of stem cells and gene enhancement to engineer cartilage has become a viable alternative to other cartilage repair methods [1,2,4]. …”

“…Joint cartilage defects resulting from degenerative disorders or traumatic injuries are difficult to treat due to the cartilage's limited capacity for self repair [1]. Numerous surgical methods have been applied in an effort to repair cartilage, reduce joint pain, and improve joint function, primarily marrow stimulating techniques and transplantation techniques [2].…”

Protein-based injectable hydrogels towards the regeneration of articular cartilage

“…bone marrow, adipose tissue, synovium, periosteum, umbilical cord vein or placenta. They also have a high expansion capacity in vitro and can be differentiated into chondrocytes under the appropriate conditions [18]. Fibroblasts are also being studied, since they can be directed towards a chondrocytic phenotype when cultured in the right conditions [19].…”

“…However, more trials need to be done to assess whether their behavior is as good as the TGF-β factors. Other growth factors currently under study are: the Fibroblast Growth Factor (FGF), Insulin Growth Factors (IGFs), the Wingless (Wnt) family and Hedgehog family [14], [18]. Other approaches aim to mediate in OA by inhibiting inflammatory mediators (IL-1 and TNF-α) or other substances that play a role in cartilage degeneration (MMPs, ADAMTS-4 and ADAMTS-5) [14].…”

“…Other approaches aim to mediate in OA by inhibiting inflammatory mediators (IL-1 and TNF-α) or other substances that play a role in cartilage degeneration (MMPs, ADAMTS-4 and ADAMTS-5) [14]. The gene therapy approach is focused on manipulating progenitor cells and chondrocytes to locally express genes that encode specific growth factors, which will enhance osteochondral repair [12], [18].…”