The musculoskeletal (MS) system consists of bone, cartilage, tendon, ligament, and skeletal muscle, which forms the basic framework of the human body. This system plays a vital role in appropriate body functions, including movement, the protection of internal organs, support, hematopoiesis, and postural stability. Therefore, it is understandable that the damage or loss of MS tissues significantly reduces the quality of life and limits mobility. Tissue engineering and its applications in the healthcare industry have been rapidly growing over the past few decades. Tissue engineering has made significant contributions toward developing new therapeutic strategies for the treatment of MS defects and relevant disease. Among various biomaterials used for tissue engineering, natural polymers offer superior properties that promote optimal cell interaction and desired biological function. Natural polymers have similarity with the native ECM, including enzymatic degradation, bio-resorb and non-toxic degradation products, ability to conjugate with various agents, and high chemical versatility, biocompatibility, and bioactivity that promote optimal cell interaction and desired biological functions. This review summarizes recent advances in applying natural-based scaffolds for musculoskeletal tissue engineering.

This study aimed to investigate the regenerative effect of decellularized osteochondral ECM xenograft in combination with various biological products in an osteochondral (OC) defect. OC tissue from the sheep femur were obtained and decellularized. The decellularized ECM (dECM) was combined with either platelet-rich fibrin (PRF), amniotic membrane extract (AME), or rabbit bone marrow-derived mesenchymal stromal cells (rBMSCs). The hybrid dECM-biological products were then utilized for the treatment of rabbit OC critical size defects. The regenerative potential of different groups was compared using; MRI, macroscopic assessment, histopathology, and histomorphometry. All characterizations analysis verified successful decellularization.Three months post-surgery, macroscopic findings indicated that dECM was better compared to controls. Also, dECM in combination with AME, PRF, and rBMSCs showed enhanced OC regeneration compared to only dECM (AME: +100%, PRF: +61%, rBMSCs: +28%). In particular, the dECM+AME group results in the best integration of new cartilage into surrounding cartilage tissue. The histomorphometric evaluations demonstrated enhancement in new cartilage formation and bone tissue (86.5 ± 5.9% and 90 ± 7.7%, respectively) for the dECM+AME group compared to other groups. Furthermore, histological results for the dECM+AME elucidated a mature hyaline cartilage tissue that covered the new and symmetrically formed subchondral bone, exhibiting a significantly higher regenerative effect compared to all other treated groups. This finding was also confirmed with MRI images. The current study revealed that in addition to the benefits of dECM alone, its combination with AME indicated to have a superior regenerative effect on OC regeneration. Overall, dECM+AME may be considered a suitable construct for treating knee OC injuries.