**Conflict of interest**

The process of wound healing is strongly influenced by the role of migration and proliferation of fibroblasts in the injury site. Indeed fibroblast is one part of ECM. The proliferation of fibroblasts determines the outcome of wound healing. Fibroblasts will produce collagen that will link to the wound, and fibroblasts will also affect the process of reepithelialization that will close the wound. Fibroblasts will produce type III collagen during proliferation and facilitate wound closure. During proliferation stage, fibroblasts proliferation activity is higher due to the presence of TGFstimulated fibroblasts to secrete bFGF. The higher number of fibroblasts also induces increasing of collagen synthesis. Collagen fiber is the major protein secreted by fibroblast, composed of extracellular matrix to replace wound tissue strength and function. Collagen fibers deposition was significant on 8–10 days after injury. The number of fibroblasts increases significantly, in cor-

Mesenchymal stem cell conditioned medium (MSCM) can be defined as secreted factor that referred to as secretome, microvesicle, or exosome without the stem cells which may found in the medium where the stem cells are growing. The use of MSCM as cell-free therapy has more significant advantages in comparison to the use of stem cells, mainly to avoid the need of HLA matching between donor and recipient as a consequence to decrease the chance of transplant rejection. Additionally, MSCM is more easy to produce and save in large quantity. The presence of human umbilical mesenchymal conditioned medium (HU-MSCM), will accelerate curing of the acute and chronic incision and/or burn wound by increasing the number of myofibroblasts and encouraging the expression of VEGF, TGF, bFGF, and also PDGF to promote wound closure. Recently, it has been mentioned that widespread neuronal cell death in the neocortex and hippocampus is an ineluctable concomitant of brain aging caused by diseases and injuries. However, recent studies suggest that neuron death also occurs in functional aging and it seems in related to an impairment of neocortical and hippocampal functions during aging processes. Data from WHO and Alzheimer report show increasing number of people suffering from dementia along with aging. Profoundly understanding the role of extracellular matrix (ECM) in influencing neurogenesis has presented novel strategies for tissue regeneration (**Figure 5**). Central nervous system injury because of stroke vascular and amyloid plaque accumulation as the effect of Alzheimer's diseases may cause the disturbance astrocytes, fibroblasts, and oligodendrocyte precursors cell proliferation which may form a glial scar [8, 9]. Within this glial scar, upregulated proteoglycans like CSPGs and changes in sulfation patterns within the

To solve the problem, some manipulation on the intrinsic extracellular matrix by using traditional herb such as *Ocimum sanctum* extract was already done. In the in vivo and in vitro model using human brain microvascular endothelial cells (HBMECs) which mimics bloodbrain barrier, the treatment of the extract may promote the cell proliferation on the hippocampus area and HBMECs in the condition upregulation of choline acetyltransferase (ChAT) enzyme [11, 12]. In addition, there is also a chance to use nanometer-sized scaffolds in the presence of other substrates such as vascular endothelial growth factor or hyaluronic acid with laminin. This scaffold may conduct a way to the regenerative capacity and functional recovery of the CNS to reconstruct formed cavities and reconnect neuronal processes. Thus, the artificial scaffold functions to enhance the communication between cells, allowing for

relation with the presence of an abundance of bFGF on 8–10 days after wounding.

70 Tissue Regeneration

ECM result in the building of regeneration inhibition [10].

The authors declare there is no conflict of interest.
