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Newts can regenerate functional elbow joints after amputation at the joint level. Previous studies have suggested the potential contribution of cells from residual tendon tissues to joint cartilage regeneration. A serum‐free tissue culture system for tendons was established to explore cell dynamics during joint regeneration. Culturing isolated tendons in this system, stimulated by regeneration‐related factors, such as fibroblast growth factor (FGF) and platelet‐derived growth factor, led to robust cell migration and proliferation. Moreover, cells proliferating in an FGF‐rich environment differentiated into Sox9‐positive chondrocytes upon BMP7 introduction. These findings suggest that FGF‐stimulated cells from tendons may aid in joint cartilage regeneration during functional elbow joint regeneration in newts. [ABSTRACT FROM AUTHOR]

Background: Cranial cruciate ligament disease is one of the leading causes of pelvic limb claudication in canines and osteoarthritis in the stifle joint. Historically, studies have focused on surgical options to improve the stability of the stifle joint, although none of the techniques described in the literature prevents the development of osteoarthritis. Aim: This study aimed at proving the presence of osteoarthritis at the time of diagnosis of cranial cruciate ligament rupture, as well as evaluating the benefits of administering diacerein or chondroprotective coadjuvants to the extracapsular fabelo-tibial technique. Methods: Seventeen dogs aged between 2 and 8, weighing more than 25 kg, with no predilection for breed or sex, were operated on using this technique. These were divided into three groups: Diacerein (DAR), Chondroprotector (CP), and Control. The animals were treated for 90 days and controlled clinically, radiologically, and using multidimensional scales for pain and quality of life. The statistical analysis used was descriptive and through non-parametric tests. Results: All patients had some degree of osteoarthritis at the beginning of the study associated with the presence of pain. The treated groups improved the claudication scores; however, the changes were significant for the diacerein group. The pain score improved in all animals, including those in the Control group; however, the differences were significant only in the treated groups. On the other hand, no significant differences were detected in the radiological studies, so it would be convenient to perform this study over more than 90 days. Conclusion: The surgical treatment accompanied by drugs that act on the degradation of articular cartilage has better clinical results. [Open Vet J 2023; 13(3.000): 297-306]

Cartilage damage affects millions of people worldwide. Tissue engineering strategies hold the promise to provide off‐the‐shelf cartilage analogs for tissue transplantation in cartilage repair. However, current strategies hardly generate sufficient grafts, as tissues cannot maintain size growth and cartilaginous phenotypes simultaneously. Herein, a step‐wise strategy is developed for fabricating expandable human macromass cartilage (macro‐cartilage) in a 3D condition by employing human polydactyly chondrocytes and a screen‐defined serum‐free customized culture (CC). CC‐induced chondrocytes demonstrate improved cell plasticity, expressing chondrogenic biomarkers after a 14.59‐times expansion. Crucially, CC‐chondrocytes form large‐size cartilage tissues with average diameters of 3.25 ± 0.05 mm, exhibiting abundant homogenous matrix and intact structure without a necrotic core. Compared with typical culture, the cell yield in CC increases 2.57 times, and the expression of cartilage marker collagen type II increases 4.70 times. Transcriptomics reveal that this step‐wise culture drives a proliferation‐to‐differentiation process through an intermediate plastic stage, and CC‐chondrocytes undergo a chondral lineage‐specific differentiation with an activated metabolism. Animal studies show that CC macro‐cartilage maintains a hyaline‐like cartilage phenotype in vivo and significantly promotes the healing of large cartilage defects. Overall, an efficient expansion of human macro‐cartilage with superior regenerative plasticity is achieved, providing a promising strategy for joint regeneration. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common degenerative joint disorder affecting millions worldwide, leading to pain, disability, and decreased quality of life. In recent years, there has been increasing interest in biological therapies, particularly platelet-rich plasma (PRP), as an alternative treatment for OA. This review explores the current evidence supporting PRP use in OA management, examining its mechanism of action, clinical outcomes, and future directions. PRP has shown promise in promoting tissue regeneration, reducing inflammation, and delaying the progression of OA. While short-term results are favorable, further research is necessary to determine its long-term efficacy and optimal application protocols. [ABSTRACT FROM AUTHOR]

Abstract Cartilage damage affects millions of people worldwide. Tissue engineering strategies hold the promise to provide off‐the‐shelf cartilage analogs for tissue transplantation in cartilage repair. However, current strategies hardly generate sufficient grafts, as tissues cannot maintain size growth and cartilaginous phenotypes simultaneously. Herein, a step‐wise strategy is developed for fabricating expandable human macromass cartilage (macro‐cartilage) in a 3D condition by employing human polydactyly chondrocytes and a screen‐defined serum‐free customized culture (CC). CC‐induced chondrocytes demonstrate improved cell plasticity, expressing chondrogenic biomarkers after a 14.59‐times expansion. Crucially, CC‐chondrocytes form large‐size cartilage tissues with average diameters of 3.25 ± 0.05 mm, exhibiting abundant homogenous matrix and intact structure without a necrotic core. Compared with typical culture, the cell yield in CC increases 2.57 times, and the expression of cartilage marker collagen type II increases 4.70 times. Transcriptomics reveal that this step‐wise culture drives a proliferation‐to‐differentiation process through an intermediate plastic stage, and CC‐chondrocytes undergo a chondral lineage‐specific differentiation with an activated metabolism. Animal studies show that CC macro‐cartilage maintains a hyaline‐like cartilage phenotype in vivo and significantly promotes the healing of large cartilage defects. Overall, an efficient expansion of human macro‐cartilage with superior regenerative plasticity is achieved, providing a promising strategy for joint regeneration.

Background: Cranial cruciate ligament disease is one of the leading causes of pelvic limb claudication in canines and osteoarthritis in the stifle joint. Historically, studies have focused on surgical options to improve the stability of the stifle joint, although none of the techniques described in the literature prevents the development of osteoarthritis. Aim: This study aimed at proving the presence of osteoarthritis at the time of diagnosis of cranial cruciate ligament rupture, as well as evaluating the benefits of administering diacerein (DAR) or chondroprotective coadjuvants to the extracapsular fabelo-tibial technique. Methods: Seventeen dogs aged between 2 and 8, weighing more than 25 kg, with no predilection for breed or sex, were operated on using this technique. These were divided into three groups: DAR, Chondroprotector (CP), and Control. The animals were treated for 90 days and controlled clinically, radiologically, and using multidimensional scales for pain and quality of life. The statistical analysis used was descriptive and through non-parametric tests. Results: All patients had some degree of osteoarthritis at the beginning of the study associated with the presence of pain. The treated groups improved the claudication scores; however, the changes were significant for the DAR group. The pain score improved in all animals, including those in the Control group; however, the differences were significant only in the treated groups. On the other hand, no significant differences were detected in the radiological studies, so it would be convenient to perform this study over more than 90 days. Conclusion: The surgical treatment accompanied by drugs that act on the degradation of articular cartilage has better clinical results. [ABSTRACT FROM AUTHOR]

Due to the absence of nerves and blood vessels in articular cartilage, its regeneration and repair present a significant and complex challenge in osteoarthritis treatment. Developing a specialized physical and chemical microenvironment supporting cell growth has been difficult in cartilage grafting, especially when aiming for comprehensive biomimetic solutions. Based on previous research, we have designed a tissue-engineered decellularized living hyaline cartilage graft (dLhCG). The study developed a method to improve the hydrophilicity and stiffness of scaffolds by employing chemical grafting techniques and designed a decellularized hyaline cartilage phenotype matrix scaffold for tissue engineering. Here, we reported a method using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride /N-hydroxysuccinimide (EDC/NHS) to achieve the grafting of chondroitin sulfate (CS) onto dLhCG, ultimately producing a tissue-engineered hyaline cartilage graft with the CS (dLhCG/CS). Young's modulus measurements revealed that the cross-linked scaffolds exhibited enhanced mechanical properties. We implanted the cross-linked dLhCG/CS scaffolds into the trochlear region of rat joints and evaluated their functionality through histological analysis and biomechanical tests. After 12 weeks, the dLhCG/CS scaffolds demonstrated excellent bioinductive activity comparable to dLhCG. The regenerated tissue effectively maintained a hyaline cartilage phenotype and exhibited similar mechanical properties, playing a crucial role in cartilage regeneration., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Amputation injuries in mammals are typically non-regenerative; however, joint regeneration is stimulated by BMP9 treatment, indicating the presence of latent articular chondrocyte progenitor cells. BMP9 induces a battery of chondrogenic genes in vivo, and a similar response is observed in cultures of amputation wound cells. Extended cultures of BMP9-treated cells results in differentiation of hyaline cartilage, and single cell RNAseq analysis identified wound fibroblasts as BMP9 responsive. This culture model was used to identify a BMP9-responsive adult fibroblast cell line and a culture strategy was developed to engineer hyaline cartilage for engraftment into an acutely damaged joint. Transplanted hyaline cartilage survived engraftment and maintained a hyaline cartilage phenotype, but did not form mature articular cartilage. In addition, individual hypertrophic chondrocytes were identified in some samples, indicating that the acute joint injury site can promote osteogenic progression of engrafted hyaline cartilage. The findings identify fibroblasts as a cell source for engineering articular cartilage and establish a novel experimental strategy that bridges the gap between regeneration biology and regenerative medicine. [ABSTRACT FROM AUTHOR]

Additive manufacturing (AM) is a promising method for fabricating customized and anatomically correct surgical implants. Advancement in design and the AM of joint replacement implants has mainly targeted implants for large joint replacement while progress in small joint replacements has been limited. This study describes a method for fabrication of porous biodegradable ceramic "templates" for use in preparing small joint implants such as the proximal interphalangeal (PIP) finger joint by combining powder-bed binder jetting (PBBJ) AM plus post-process sintering. A proposed PIP template design was selected using finite element analysis (FEA) to predict a suitable design for reliable fixation of the implant to host bone through bone ingrowth while providing necessary mechanical properties to avoid implant fracture during anticipated in vivo functional loading. Calcium polyphosphate (CPP) ceramic powder was selected for fabrication of the porous biodegradable ceramic templates intended to degrade in vivo in time to be replaced by bone while retaining a mature articular cartilage layer anchored to the intended joint bearing surface thereby achieving whole joint regeneration. For the AM build-up, density and mechanical strength of porous AM-made samples were optimized by varying the binder saturation level in the PBBJ process. Using the preferred design and processing conditions, PIP joint templates were made and subjected to preliminary fatigue testing to demonstrate survival under anticipated in vivo functional loading conditions. The study has demonstrated the potential of this novel approach for the preparation of implants for use in small digit joint regeneration. [ABSTRACT FROM AUTHOR]

Increasing research attention has focused on the use of stem cells (SCs) in regenerative and reparative medicine. Adipose-derived regenerative cells (ADRCs) are a relatively cheap and ethical source of SCs. Temporomandibular disorders (TMDs) have been reported with rising incidence over recent decades. The main aims of this study were to evaluate the effects of ADRCs application on the healing of both soft and hard temporomandibular joint (TMJ) tissues, and to assess the possible utilization of ADRCs in TMD treatment. We investigated the effects of human ADRCs on the healing of TMJ defects in immunodeficient rabbits. With no prior cultivation, ADRCs were applied to a surgically created defect in the cartilage of a rabbit TMJ. The healing process and inflammatory response were examined. Our results indicated that ADRCs supported repair processes in soft tissues. However, ADRC treatment induced a significant immune response in both soft and hard tissues, with hard tissues showing a higher level of bone remodelling. Non-differentiated ADRCs can be a promising tool for regenerative medicine of TMJ; however, deeper understanding of their effect on the cellular level is needed. [ABSTRACT FROM AUTHOR]

Background: Cranial cruciate ligament disease is one of the leading causes of pelvic limb claudication in canines and osteoarthritis in the stifle joint. Historically, studies have focused on surgical options to improve the stability of the stifle joint, although none of the techniques described in the literature prevents the development of osteoarthritis., Aim: This study aimed at proving the presence of osteoarthritis at the time of diagnosis of cranial cruciate ligament rupture, as well as evaluating the benefits of administering diacerein (DAR) or chondroprotective coadjuvants to the extracapsular fabelo-tibial technique., Methods: Seventeen dogs aged between 2 and 8, weighing more than 25 kg, with no predilection for breed or sex, were operated on using this technique. These were divided into three groups: DAR, Chondroprotector (CP), and Control. The animals were treated for 90 days and controlled clinically, radiologically, and using multidimensional scales for pain and quality of life. The statistical analysis used was descriptive and through non-parametric tests., Results: All patients had some degree of osteoarthritis at the beginning of the study associated with the presence of pain. The treated groups improved the claudication scores; however, the changes were significant for the DAR group. The pain score improved in all animals, including those in the Control group; however, the differences were significant only in the treated groups. On the other hand, no significant differences were detected in the radiological studies, so it would be convenient to perform this study over more than 90 days., Conclusion: The surgical treatment accompanied by drugs that act on the degradation of articular cartilage has better clinical results., Competing Interests: The Authors declare that there is no conflict of interest.

Abstract: Synovial joints are among the most important structures that give us complex motor abilities as humans. Degenerative joint diseases, such as arthritis, cause loss of normal joint functioning and affect over 40 million people in the USA and approximately 350 million people worldwide. Therapies based on regenerative medicine hold the promise of effectively repairing or replacing damaged joints permanently. Here, for the first time, we introduce a model for synovial joint regeneration utilizing the chick embryo. In this model, a block of tissue that contains the prospective elbow is excised, leaving a window with strips of anterior and posterior tissue intact (window excision, WE). In contrast, we also slice out the same area containing the elbow and the distal piece of the limb is pinned back onto the stump (slice excision, SE). Interestingly, when the elbow is removed via WE, regeneration of the joint takes place, whereas the elbow joint does not regenerate following SE. In order to investigate whether the regeneration response recapitulates the developmental program of forming joints, we used GDF-5 and Autotaxin (Atx) as joint tissue specific markers, and Sox-9 and Col-9 as cartilage markers for in situ hybridization on sections at different time points after WE and SE surgeries. Re-expression of GDF-5 and Atx is observed in the WE samples by 60h after surgery. In contrast, the majority of the samples that underwent SE surgery did not express GDF-5 and Atx. Also, in SE fusion of cartilage elements takes place and the joint interzone does not form. This is indicated by continuous Col-9 expression in SE limbs, whereas Col-9 is downregulated at the joint interzone in the regenerating WE samples. This order and pattern of gene expression observed in regenerates is similar to the development of a joint suggesting that regeneration recapitulates development at the molecular level. This model defines some of the conditions required for inducing joint regeneration in an otherwise nonregenerating environment. This knowledge can be useful for designing new therapeutic approaches for joint loss or for conditions affecting joint integrity in humans. [Copyright &y& Elsevier]

Amputation injuries in mammals are typically non-regenerative; however, joint regeneration is stimulated by BMP9 treatment, indicating the presence of latent articular chondrocyte progenitor cells. BMP9 induces a battery of chondrogenic genes in vivo, and a similar response is observed in cultures of amputation wound cells. Extended cultures of BMP9-treated cells results in differentiation of hyaline cartilage, and single cell RNAseq analysis identified wound fibroblasts as BMP9 responsive. This culture model was used to identify a BMP9-responsive adult fibroblast cell line and a culture strategy was developed to engineer hyaline cartilage for engraftment into an acutely damaged joint. Transplanted hyaline cartilage survived engraftment and maintained a hyaline cartilage phenotype, but did not form mature articular cartilage. In addition, individual hypertrophic chondrocytes were identified in some samples, indicating that the acute joint injury site can promote osteogenic progression of engrafted hyaline cartilage. The findings identify fibroblasts as a cell source for engineering articular cartilage and establish a novel experimental strategy that bridges the gap between regeneration biology and regenerative medicine., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Hyperacute serum (HAS) is a blood derivative product that promotes the proliferation of various cell types and controls inflammation in vitro. The aim of this study is to investigate the regenerative potential of different formulations of HAS, including lyophilized and hyaluronic acid combined versions, to obtain a stable and standardized therapeutic in osteoarthritis (OA), which may be able to overcome the variability limitations of platelet-rich plasma (PRP). Primary human osteoarthritic chondrocytes were used for testing cellular viability and gene expression of OA-related genes. Moreover, a co-culture of human explants of cartilage, bone and synovium under inflammatory conditions was used for investigating the inflammatory control capacities of the different therapeutics. In this study, one formulation of lyophilized HAS achieved the high cell viability rates of liquid HAS and PRP. Gene expression analysis showed that HAS induced higher Col1a1 expression than PRP. Cytokine quantification from supernatant fluids revealed that HAS treatment of inflamed co-cultures significantly reduced levels of IL-5, IL-15, IL-2, TNFα, IL-7 and IL-12. To conclude, lyophilized HAS is a stable and standardized therapeutic with high potential in joint regeneration. [ABSTRACT FROM AUTHOR]