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Osteoarthritis (OA) is a prominent cause of disability, and has severe social and economic ramifications across the globe. The main driver of OA’s pervasiveness is the fact that no current medical interventions exist to reverse or even attenuate the degeneration of cartilage within the articular joint. Crucial for cell-to-cell communication, extracellular vesicles (EVs) contribute to OA progression through the delivery of bioactive molecules in the inflammatory microenvironment. By repurposing this acellular means of signal transmission, therapeutic drugs may be administered to degenerated cartilage tissue in the hopes of encouraging regeneration. Positive outcomes are apparent in in vivo studies on this subject; however, for this therapy to prove itself in the clinical world, efforts towards standardizing the characterization, application, biological contents, and dosage are essential.

Chitosan (CS), a biopolymer, holds significant potential in bone regeneration due to its biocompatibility and biodegradability attributes. While crustacean-derived CS is conventionally used in research, there is growing interest in fungal-derived CS for its equally potent properties in bone regenerative applications. Here, we investigated the physicochemical and biological characteristics of fungal (MDC) and crustacean (ADC)-derived CS scaffolds embedded with different concentrations of tricalcium phosphate minerals (TCP), i.e., 0(wt)%: ADC/MDC-1, 10(wt)%: ADC/MDC-2, 20(wt)%: ADC/MDC-3 and 30(wt)%: ADC/MDC-4. ADC-1 and MDC-1 lyophilised scaffolds lacking TCP minerals presented the highest zeta potentials of 47.3 ± 1.2 mV and 55.1 ± 1.6 mV, respectively. Scanning electron microscopy revealed prominent distinctions whereby MDC scaffolds exhibited striation-like structural microarchitecture in contrast to the porous morphology exhibited by ADC scaffold types. With regard to the 4-week scaffold mass reductions, MDC-1, MDC-2, MDC-3, and MDC-4 indicated declines of 55.98 ± 4.2%, 40.16 ± 3.6%, 27.05 ± 4.7%, and 19.16 ± 5.3%, respectively. Conversely, ADC-1, ADC-2, ADC-3, and ADC-4 presented mass reductions of 35.78 ± 5.1%, 25.19 ± 4.2%, 20.23 ± 6.3%, and 13.68 ± 5.4%, respectively. The biological performance of the scaffolds was assessed through in vitro bone marrow mesenchymal stromal cell (BMMSCs) attachment via indirect and direct cytotoxicity studies, where all scaffold types presented no cytotoxic behaviours. MDC scaffolds indicated results comparable to ADC, where both CS types exhibited similar physiochemical properties. Our data suggest that MDC scaffolds could be a potent alternative to ADC-derived scaffolds for bone regeneration applications, particularly for 10(wt)% TCP concentrations.

Osteoarthritis (OA) is a degenerative joint disease, causing impaired mobility. There are currently no effective therapies other than palliative treatment. Mesenchymal stromal cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) have shown promise in attenuating OA progression, promoting chondral regeneration, and modulating joint inflammation. However, the precise molecular mechanism of action driving their beneficial effects has not been fully elucidated. In this study, we analyzed MSC-EV-treated human OA chondrocytes (OACs) to assess viability, proliferation, migration, cytokine and catabolic protein expression, and microRNA and mRNA profiles. We observed that MSC-EV-treated OACs displayed increased metabolic activity, proliferation, and migration compared to the controls. They produced decreased proinflammatory (Il-8 and IFN-γ) and increased anti-inflammatory (IL-13) cytokines, and lower levels of MMP13 protein coupled with reduced expression of MMP13 mRNA, as well as negative microRNA regulators of chondrogenesis (miR-145-5p and miR-21-5p). In 3D models, MSC-EV-treated OACs exhibited enhanced chondrogenesis-promoting features (elevated sGAG, ACAN, and aggrecan). MSC-EV treatment also reversed the pathological impact of IL-1β on chondrogenic gene expression and extracellular matrix component (ECM) production. Finally, MSC-EV-treated OACs demonstrated the enhanced expression of genes associated with cartilage function, collagen biosynthesis, and ECM organization and exhibited a signature of 24 differentially expressed microRNAs, associated with chondrogenesis-associated pathways and ECM interactions. In conclusion, our data provide new insights on the potential mechanism of action of MSC-EVs as a treatment option for early-stage OA, including transcriptomic analysis of MSC-EV-treated OA, which may pave the way for more targeted novel therapeutics.

Bone void-filling cements are one of the preferred materials for managing irregular bone voids, particularly in the geriatric population who undergo many orthopedic surgeries. However, bone marrow mesenchymal stem/stromal cells (BM-MSCs) of older-age donors often exhibit reduced osteogenic capacity. Hence, it is crucial to evaluate candidate bone substitute materials with BM-MSCs from the geriatric population to determine the true osteogenic potential, thus simulating the clinical situation. With this concept, we investigated the osteogenic potential of shell nacre cement (SNC), a bone void-filling cement based on shell nacre powder and ladder-structured siloxane methacrylate, using older donor BM-MSCs (age > 55 years) and young donor BM-MSCs (age < 30 years). Direct and indirect cytotoxicity studies conducted with human BM-MSCs confirmed the non-cytotoxic nature of SNC. The standard colony-forming unit-fibroblast (CFU-F) assay and population doubling (PD) time assays revealed a significant reduction in the proliferation potential (p < 0.0001, p < 0.05) in older donor BM-MSCs compared to young donor BM-MSCs. Correspondingly, older donor BM-MSCs contained higher proportions of senescent, β-galactosidase (SA-β gal)-positive cells (nearly 2-fold, p < 0.001). In contrast, the proliferation capacity of older donor BM-MSCs, measured as the area density of CellTrackerTM green positive cells, was similar to that of young donor BM-MSCs following a 7-day culture on SNC. Furthermore, after 14 days of osteoinduction on SNC, scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS) showed that the amount of calcium and phosphorus deposited by young and older donor BM-MSCs on SNC was comparable. A similar trend was observed in the expression of the osteogenesis-related genes BMP2, RUNX2, ALP, COL1A1, OMD and SPARC. Overall, the results of this study indicated that SNC would be a promising candidate for managing bone voids in all age groups.

Aging and age-related changes impact the quality of life (QOL) in elderly with a decline in movement, cognitive abilities and increased vulnerability towards age-related diseases (ARDs). One of the key contributing factors is cellular senescence, which is triggered majorly by DNA damage response (DDR). Accumulated senescent cells (SCs) release senescence-associated secretory phenotype (SASP), which includes pro-inflammatory cytokines, matrix metalloproteinases (MMPs), lipids and chemokines that are detrimental to the surrounding tissues. Chronic low-grade inflammation in the elderly or inflammaging is also associated with cellular senescence and contributes to ARDs. The literature from the last decade has recorded the use of platelet rich plasma (PRP) to combat senescence and inflammation, alleviate pain as an analgesic, promote tissue regeneration and repair via angiogenesis—all of which are essential in anti-aging and tissue regeneration strategies. In the last few decades, platelet-rich plasma (PRP) has been used as an anti-aging treatment option for dermatological applications and with great interest in tissue regeneration for orthopaedic applications, especially in osteoarthritis (OA). In this exploration, we connect the intricate relationship between aging, ARDs, senescence and inflammation and delve into PRP’s properties and potential benefits. We conduct a comparative review of the current literature on PRP treatment strategies, paying particular attention to the instances strongly linked to ARDs. Finally, upon careful consideration of this interconnected information in the context of aging, we suggest a prospective role for PRP in developing anti-aging therapeutic strategies.

Periodontitis and diabetes mellitus (DM) are two of the most common and challenging health problems worldwide and they affect each other mutually and adversely. Current periodontal therapies have unpredictable outcome in diabetic patients. Periodontal tissue engineering is a challenging but promising approach that aims at restoring periodontal tissues using one or all of the following: stem cells, signalling molecules and scaffolds. Mesenchymal stem cells (MSCs) and insulin-like growth factor (IGF) represent ideal examples of stem cells and signalling molecules. This review outlines the most recent updates in characterizing MSCs isolated from diabetics to fully understand why diabetics are more prone to periodontitis that theoretically reflect the impaired regenerative capabilities of their native stem cells. This characterisation is of utmost importance to enhance autologous stem cells based tissue regeneration in diabetic patients using both MSCs and members of IGF axis.

Bone marrow (BM) is a reliable source of multipotent mesenchymal stromal cells (MSCs), which have been successfully used for treating osteonecrosis. Considering the functional advantages of BM-MSCs as bone and cartilage reparatory cells and supporting angiogenesis, several donor-related factors are also essential to consider when autologous BM-MSCs are used for such regenerative therapies. Aging is one of several factors contributing to the donor-related variability and found to be associated with a reduction of BM-MSC numbers. However, even within the same age group, other factors affecting MSC quantity and function remain incompletely understood. For patients with osteonecrosis, several underlying factors have been linked to the decrease of the proliferation of BM-MSCs as well as the impairment of their differentiation, migration, angiogenesis-support and immunoregulatory functions. This review discusses the quality and quantity of BM-MSCs in relation to the etiological conditions of osteonecrosis such as sickle cell disease, Gaucher disease, alcohol, corticosteroids, Systemic Lupus Erythematosus, diabetes, chronic renal disease and chemotherapy. A clear understanding of the regenerative potential of BM-MSCs is essential to optimize the cellular therapy of osteonecrosis and other bone damage conditions.