Review
Special Issue: Celebrating 30 years of biotechnology
Extracellular matrix scaffolds for cartilage and bone regeneration

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Regenerative medicine approaches based on decellularized extracellular matrix (ECM) scaffolds and tissues are rapidly expanding. The rationale for using ECM as a natural biomaterial is the presence of bioactive molecules that drive tissue homeostasis and regeneration. Moreover, appropriately prepared ECM is biodegradable and does not elicit adverse immune responses. Successful clinical application of decellularized tissues has been reported in cardiovascular, gastrointestinal, and breast reconstructive surgery. At present, the use of ECM for osteochondral tissue engineering is attracting interest. Recent data underscore the great promise for future application of decellularized ECM for osteochondral repair. This review describes the rationale for using ECM-based approaches for different regenerative purposes and details the application of ECM for cartilage or osteochondral repair.

Highlights

ā–ŗ Extracellular matrix scaffolds provide a bioactive platform for tissue regeneration. ā–ŗ Osteochondral defect repair remains a great orthopedic and socioeconomic burden. ā–ŗ We describe cartilage and bone decellularization and possible future directions. ā–ŗ Extracellular matrix scaffolds hold great promise for osteochondral defect repair.

Section snippets

The need for improved repair of osteochondral defects

Joint injuries are common in the young and active population and often result in cartilage or osteochondral lesions. If untreated, these defects lead to joint swelling, pain, and serious restrictions in daily activities and can eventually progress towards osteoarthritis (OA), of which the only end-stage, salvaging therapy is artificial joint replacement. Over 151 million people suffer from OA worldwide [1], representing a huge clinical and socioeconomic burden. Established OA is notoriously

ECM-based regenerative medicine

All tissues are composed of cells surrounded by ECM that consists of a unique and tissue-specific 3D environment of structural and functional molecules secreted by the resident cells [14]. There is reciprocal interaction between cells and ECM; cellular products, including proteinases, modify the ECM, and ECM-incorporated growth factors and cytokines act as functional cues, steering the metabolic and secretory activity of cells. This situation becomes even more complex because the intricate

Application of ECM-based scaffolds to treat osteochondral defects

Treatments during which osteochondral plugs, taken either from a non-load-bearing region of the joint (mosaicplasty) or from a donor (allogeneic osteochondral grafting), are used to fill the defect can theoretically be considered ECM-based strategies because they imply the direct implantation of cartilage and bone matrix (Figure 1). However, the use of seeded or unseeded ECM-based scaffolds is a new and emerging approach within the field of cartilage tissue engineering, supported by a slowly

Future perspectives for ECM-based scaffolds for osteochondral repair

The use of decellularized ECM is gaining ground within the field of cartilage tissue engineering and may prove to be of great potential because it allows for multifactorial mimicry that has not yet been achieved by man-made biomaterials. The approach is still relatively underexplored and extensive research is required to understand the biologic responses to ECM scaffolds within the joint environment and to optimize the decellularization techniques and ultimately the final repair tissue. There

Concluding remarks

ECM scaffolds have shown great promise within the field of tissue engineering and are now being developed specifically for cartilage repair. Decellularized ECM-based scaffolds may solve many problems associated with the matrix-based approaches currently used for the repair of cartilage or osteochondral defects, such as osteochondral allografting and mosaicplasty. This approach may lead to the development of the ideal cartilage or osteochondral scaffold, providing the injured site with the right

Glossary

Allograft
graft obtained from a donor of the same species.
bFGF
basic fibroblast growth factor; involved in angiogenesis, wound healing, and embryonic development.
EGF
epidermal growth factor; stimulates proliferation and differentiation.
IGF
insulin-like growth factor; regulates cellular proliferation and apoptosis.
Mosaicplasty
surgical procedure during which a defect is filled with osteochondral plugs taken from a non-load-bearing region of the joint.
Osseous phase
bone compartment.
Proteoglycans

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