Gang Zhong

Mitochondria are the key biological generators of eukaryotic cells, controlling the energy supply while providing many important biosynthetic intermediates. Mitochondria act as a dynamic, functionally and structurally interconnected network hub closely integrated with other cellular compartments via biomembrane systems, transmitting biological information by shuttling between cells and tissues. Defects and dysregulation of mitochondrial functions are critically involved in pathological mechanisms contributing to aging, cancer, inflammation, neurodegenerative diseases, and other severe human diseases. Mediating and rejuvenating the mitochondria may therefore be of significant benefit to prevent, reverse, and even treat such pathological conditions in patients. The goal of this review is to present the most advanced strategies using mitochondria to manage such disorders and to further explore innovative approaches in the field of human mitochondria-based therapies.

The meniscus is a kind of fibrous cartilage structure that serves as a cushion in the knee joint to alleviate the mechanical load. It is commonly injured, but it cannot heal spontaneously. Traditional meniscectomy is not currently recommended as this treatment tends to cause osteoarthritis. Due to their good biocompatibility and versatile regulation, hydrogels are emerging biomaterials in tissue engineering. Hydrogels are excellent candidates in meniscus rehabilitation and regeneration because they are fine-tunable, easily modified, and capable of delivering exogenous drugs, cells, proteins, and cytokines. Various hydrogels have been reported to work well in meniscus-damaged animals, but few hydrogels are effective in the clinic, indicating that hydrogels possess many overlooked problems. In this review, we summarize the applications and problems of hydrogels in extrinsic substance delivery, meniscus rehabilitation, and meniscus regeneration. This study will provide theoretical guidance for new therapeutic strategies for meniscus repair.

Osteoarthritis (OA) is a severe, common chronic orthopaedic disorder characterised by a degradation of the articular cartilage with an incidence that increases over years. Despite the availability of various clinical options, none can stop the irreversible progression of the disease to definitely cure OA. Various mutations have been evidenced in the mitochondrial DNA (mtDNA) of cartilage cells (chondrocytes) in OA, leading to a dysfunction of the mitochondrial oxidative phosphorylation processes that significantly contributes to OA cartilage degeneration. The mitochondrial genome, therefore, represents a central, attractive target for therapy in OA, especially using genome editing procedures. In this narrative review article, we present and discuss the current advances and breakthroughs in mitochondrial genome editing as a potential, novel treatment to overcome mtDNA-related disorders such as OA. While still in its infancy and despite a number of challenges that need to be addressed (barriers to effective and site-specific mtDNA editing and repair), such a strategy has strong value to treat human OA in the future, especially using the groundbreaking clustered regularly interspaced short palindromic repeats (CRIPSR)/CRISPR-associated 9 (CRISPR/Cas9) technology and mitochondrial transplantation approaches.

Meniscal injuries have poor intrinsic healing capability and are associated with the development of osteoarthritis. Decellularized meniscus extracellular matrix (mECM) has been suggested to be efficacious for the repair of meniscus defect. However, main efforts to date have been focused on the concentration, crosslinking density and anatomical region dependence of the mECM hydrogels on regulation of proliferation and differentiation of adult mesenchymal stem cells (MSCs) in vitro 2D or 3D culture. A systematic investigation and understanding of the effect of mECM on encapsulated MSCs response and integrative meniscus repair by in vivo rat subcutaneous implantation and orthotopic meniscus injury model will be highly valuable to explore its potential for clinical translation. In this study, we investigated the in situ delivery of rat BMSCs in an injectable mECM hydrogel to a meniscal defect in a SD rat model. Decellularized mECM retained essential proteoglycans and collagens, and significantly upregulated expression of fibrochondrogenic markers by BMSCs versus collagen hydrogel alone in vitro 3D cell culture. When applied to an orthotopic model of meniscal injury in SD rat, mECM is superior than collagen I scaffold in reduction of osteophyte formation and prevention of joint space narrowing and osteoarthritis development as evidenced by histology and micro-CT analysis. Taken together, these results indicate mECM hydrogel is a highly promising carrier to deliver MSCs for long-term repair of meniscus tissue, while preventing the development of osteoarthritis.