The objective of tissue engineering is to induce tissue regeneration at damaged tissues or organs for medical therapy by making use of the self-healing potential of the living body. This tissue regeneration can be achieved with cells and the local environment which promotes their natural process of proliferation and differentiation. To build up the local environment of cell-induced tissue regeneration, it is important to develop drug delivery system (DDS) which allows bio-signal molecules (growth factors and genes) to deliver to the target cells for a certain period of time at a desired concentration. DDS technologies enhance and prolong the in vivo biological functions of bio-signal molecules for tissue regeneration. When applied to the site to be regenerated in surgically (surgical tissue engineering), DDS technology has achieved the regeneration of various tissues. The current chapter introduces a new concept of DDS-based tissue engineering for therapy of chronic fibrotic diseases. For this physical tissue engineering, fibrotic tissue is loosened or digested by the physical drug therapy to convert into an in vivo environment which can be naturally repaired by the regeneration potential of the surrounding healthy tissue. The DDS of bio-signal molecules facilitates the regeneration and repairing processes of disease fibrosis.