Next Generation Approaches for Cartilage Regeneration

Dear Colleagues, 

Osteoarthritis (OA) is a leading cause of disability in middle-aged and elderly populations globally. According to the World Health Organization, approximately 528 million people were affected by osteoarthritis in 2019—representing a 113% increase since 1990. With a current prevalence of around 15%, osteoarthritis cases are expected to rise due to aging populations, increasing obesity rates, and the growing incidence of joint injuries. Critically, no existing treatment can halt or reverse osteoarthritis  progression, and end-stage disease often requires invasive joint replacement, highlighting an urgent need for effective cartilage repair strategies. 

Cartilage was initially regarded as a tissue amenable to engineering, with early cell-based approaches designed to regenerate tissue that matches the mechanical, biological, and histological properties of native cartilage. However, decades of research have revealed persistent challenges: conventional engineering strategies lack long-term regenerative efficacy and exhibit poor cost-effectiveness compared to traditional interventions. To address these limitations, next-generation approaches for cartilage regeneration are now integrating biopharmaceutical principles—including biomaterials optimized to mimic native cartilage microenvironments, bioactive molecules (e.g., peptides, proteins, nucleic acids) that modulate chondrogenic signaling, and gene engineering strategies tailored to induce stable chondrogenic phenotypes. Additionally, mechanical stimulation is being leveraged to enhance the structural functionality of tissue-engineered constructs, while novel methods aim to recapitulate native cartilage developmental pathways—all with a focus on linking engineering design to therapeutic molecular mechanisms.

This Special Issue aims to compile cutting-edge research that bridges regenerative strategies for cartilage repair with biopharmaceutical innovation. We particularly emphasize work that highlights the therapeutic and molecular underpinnings of next-generation approaches: for example, the mechanism of action and pharmacological potential of bioactive molecules in chondrogenesis, the biopharmaceutical applications of stem cell/gene engineering (beyond structural tissue engineering), and how biomaterials enhance the delivery, stability, or efficacy of therapeutic interventions. We invite submissions of original research, review articles, and preclinical/clinical evaluation studies that advance understanding of the following: (1) molecular targets and signaling pathways governing cartilage development and repair; (2) design and optimization of biopharmaceutical-based approaches (e.g., peptide/protein/nucleic acid therapies, engineered cell products) for cartilage engineering; (3) preclinical validation of regenerative strategies with translational potential; (4) integration of biomaterials with therapeutic agents to improve cartilage repair outcomes.

I look forward to your valuable contributions that drive the translation of next-generation cartilage regeneration approaches into clinically impactful therapies.

Dr. Valeria Graceffa
Dr. Liam Morris
Guest Editors

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