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Cartilage repair and regeneration

Articular cartilage can be damaged by trauma or degraded by different forms of arthritis. Once damaged, cartilage is challenging to repair and currently impossible to fully regenerate. Advances including the discovery of new types of skeletal stem cells and the introduction of gene therapy approaches to repair damaged cartilage are placing cartilage repair and regeneration in the spotlight.

This Collection contains Research, Reviews and News articles from several Nature journals that cover the latest advances in basic cartilage research, as well as insights into cartilage repair and potential regeneration strategies.

News and Comment

Cartilage has a limited healing capacity; however, studies into the basic biological characteristics, formation and structural maintenance of the cartilage collagen network are providing explanations for the failure of current therapeutic approaches, urging us to rethink our approach to the regeneration of articular cartilage.

Comment | | Nature Reviews Rheumatology

Bone elongation requires the maintenance of a growth plate of cartilage. Two studies have now identified stem cells specific to this structure that give rise to both cartilage cells and bone-marrow stem cells.

News & Views | | Nature

After more than 25 years of development, arthritis gene therapy is finally entering clinical practice. In South Korea, a gene therapeutic has been approved for the treatment of osteoarthritis, and other gene therapeutics are in the pipeline elsewhere. Genetic medicines for arthritis should enter the rheumatological armamentarium in the foreseeable future.

Comment | | Nature Reviews Rheumatology

Regeneration of articular cartilage has been a long-standing challenge in the field of regenerative medicine. In the past 2 years, several studies have genetically identified the presence of stem cells in the surface of articular cartilage, but questions remain as to the healing properties of these cells.

News & Views | | Nature Reviews Rheumatology

Like the mythical eagle devouring Prometheus's liver as fast as it regrew, chronic inflammation hinders cartilage regeneration in inflammatory arthritis. Using stem cells engineered to secrete anti-inflammatory molecules in response to local inflammatory factors could provide a way to keep the eagle at bay as the stem cells differentiate into chondrocytes.

News & Views | | Nature Reviews Rheumatology

Reviews

Intra-articular therapies for knee osteoarthritis (OA) are causing excitement among clinicians and patients, but care should be taken when choosing which therapy to use. In this Review, Vangsness and colleagues critically appraise current and future intra-articular therapies for knee OA.

Review Article | | Nature Reviews Rheumatology

In this Review, the role of canonical Wnt signalling in articular cartilage is discussed, along with the regulatory mechanisms that exist to fine-tune Wnt signalling and the rationale for developing drugs that modulate Wnt signalling for the treatment of joint diseases such as osteoarthritis.

Review Article | | Nature Reviews Rheumatology

Research and Protocols

Arthroplasty is the main clinical option for the treatment of osteoarticular lesions, but has limited efficacy. Here, the authors use a wound dressing with autologous mesenchymal stromal cells, functionalised for local BMP2 delivery, and show feasibility and safety in standardised preclinical tests in animal models, suggesting suitability for use in clinical trials.

Article | Open Access | | Nature Communications

Priti Prasanna Maity et al. develop a method for high-yield isolation of type II collagen from the Capra hircus ear cartilage, a commonly available biowaste product. Using mass spectrometry they mapped the positions of hydroxyproline within the collagen II alpha chain; this methodology facilitates isolation and characterization of this biomedical resource.

Article | Open Access | | Communications Biology

Clonal genetic tracing is used to demonstrate that, in mice, longitudinal bone growth during fetal and neonatal periods relies on the gradual consumption of chondroprogenitors, whereas in adults, a stem cell niche is formed allowing renewing of chondroprogenitors and leading to formation of large, stable monoclonal columns of chondrocytes.

Letter | | Nature

Tools to investigate a wide range of 3D microenvironmental parameters are important for understanding and controlling cell fate. Here, the authors develop hydrogels with orthogonal biochemical gradients and use this screening system to identify microenvironments that induce mesenchymal stem cell chondrogenesis.

Article | Open Access | | Nature Communications

Dense connective tissues do not easily heal, in part due to a low supply of reparative cells. Here, the authors develop a fibrous scaffold for meniscal repair that sequentially releases collagenase and a growth factor at the injury site, breaking down the extracellular matrix and recruiting endogenous cells.

Article | Open Access | | Nature Communications

Natural materials such as cartilage and skin have a combination of toughness (meaning they are hard to fracture) and stiffness (meaning they are resistant to bending) that is difficult to emulate in synthetic hydrogels. Previously reported tough hydrogels owed their toughness to their ability to deform by stretching, but they lacked stiffness. Here Joerg Tiller and colleagues create hydrogels that are both tough and stiff by generating in situ amorphous calcium phosphate nanoparticles that are homogenously distributed throughout the hydrogel matrix. The resulting structures are tougher than most water-swollen synthetic hydrogels, and are stiffer than their natural counterparts. The highly filled composite materials can even be designed to be optically transparent, and they remain stretchable even when notched with a razor blade. The researchers attribute the stiffness of these materials to the formation of a percolated network of the calcium phosphate nanoparticles throughout the hydrogel.

Letter | | Nature