High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells

BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

A biomimetic bi-layered tissue engineering scaffolds for osteochondral defects repair

Osteochondral defects are most commonly characterized by damages to both cartilage and underlying subchondral bone tissues,thus developing bi-layered scaffold that can concurrently regenerate these two specific lineages becomes challenge.In this study,the highly biomimetic bi-layered scaffolds were successfully prepared using human-like-collagen(HLC),hyaluronan(HA)and nano hydroxyapatite(HAP)particles,combined with"liquid phase synthesis"technology,freeze-drying and chemical crosslinking techniques,which was simulated the composition of natural extracellular matrix to repair osteochondral defects.This novel bilayer osteochondral graft had a seamlessly integrated layer structure,suitable pore size,high levels of porosity,and excellent mechanical properties.In vitro cell experiments of the bilayer scaffold indicated that the scaffold could promote the proliferation and adhesion of human bone marrow mesenchymal stem cells.In vivo osteochondral defects and micro-CT experiment revealed that bilayer scaffolds showed complete closure of the defect.Histology confirmed collagen and glycosaminoglycans were deposited in the new matrix of hyaline cartilage and bone in the bilayer scaffold group.Therefore,the developed bionic bilayer scaffold enhanced the regeneration of hyaline cartilage through subchondral bone formation and lateral host-tissue integration.In conclusion,this bilayer scaffold based on HLC could be used as the desired strategy for osteochondral defects regeneration.