**1. Introduction**

Repair and regeneration are one of the most complex multi-cellular physiological processes in human body. These are responsible for restitution of normal structure and function in the body. The complex biological course occurs in a cascade of events wherein the release and action of one chemical substance causes the release/inhibition of the other. The substances released in the course of action are chemical mediators causing migration, infiltration, proliferation, and differentiation of the cells to culminate in an inflammatory response, formation of a new tissue and finally wound closure [1]. The entire procedure is a well synchronized one regulated by a signaling network. This network is a self regulatory system controlled by several growth factors, cytokines and chemokines.

Growth factors are substances released by the body at various stages of tissue healing. Healing is a coordinated process that involves harmonized efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets [1]. Cytokines and Chemokines act by activating the migration of [mainly] inflammatory cells to the wound site up regulating their own production.

By definition inflammation is redness, swelling, pain, and/or a feeling of heat in an area of the body. This is a protective reaction of the tissues to injury, disease, or

irritation [2]. This reaction is exhibited by every cell of body in an attempt to control/ prevent the tissues from further injury. It also initiates recovery of the damaged tissues.

It is initiated in any cell of the body after a tissue injury. This injury can have various end results including death of the tissue to complete restoration of form and function. However, general injuries usually result in an intermediate outcome, i.e., partial tissue regeneration, fibrosis, and/or chronic inflammation [3].

Chronic wounds are defined as; 'defects that have not proceeded through orderly and timely repair to regain structural and functional integrity. Since any lesion has the potential to become chronic, chronic wounds are classified on the basis of their underlying cause'. Apart from compromised nutritional or immunological status and advanced age; vascular insufficiency, diabetes mellitus, and local-pressure effects are the major causes for wounds to become chronic non healing wounds [4].

When bone is subjected to trauma or an adverse stimulus, the resident cells release numerous cytokines, chemokines, and other substances that initiate local vasodilatation and efflux of inflammatory cells from the circulation. This terminates the adverse event and initiates the healing process [3]. Bone healing and bone formation is explained under 3 basic principles of: Osteoinduction, Osteogenesis and Osteoconduction.

Bone matrix stores growth factors that activate and maintain cellular processes during bone formation and healing. These growth factors are potent enough to accelerate bone formation and bone healing when applied locally to both intact and healing bone tissue. Normally, these proteins are produced by osteoblasts and incorporated into the extracellular matrix during bone formation, but many times, small amounts remain trapped into the matrix. Then these bone growth factors exhibit their effects by stimulating neighboring bone cells to proliferate and increase matrix protein synthesis [5–7].

Smoking, diabetes, or radiation therapy in patients with compromised local or systemic vascularity pose clinical challenge to bone grafts and dental implants due to impaired bone healing and an increase in peri implant complication [8, 9]. The success of dental implants essentially depends on adequate bone volume, density, and vascularity [10].

## **2. Cascade of wound healing**

It takes a well managed system to control the secretion and migration of mediators to their correct places. Also a self regulatory feedback system ensures inhibition of right molecules at the right time. As soon as an injury takes place, bleeding is induced, all organisms including humans evoke an immediate, programmed, nonantigen specific immune response to preserve the organism's integrity and re-establish homeostasis [3].

In the **Table 1** [1, 10] we can have a quick brush through the events involved and release of growth factors at specific time to initiate specific actions in a healing cascade in the body.

This outline of the flow or spontaneity of the release of the various growth factors at the wound site illustrate the importance of each factor that is released at a specified time. As completion of one episode initiate second one. Thus the beginning of this process requires an injury of any/all tissues in the body.

As we talk about dental implants, it is implicated that we implant a foreign body, that is inert enough not to cause any antigenic activity, into the bone after creating

**Table 1.**

*Sequential release of growth factors to initiate and terminate healing.*

an osteotomy site. This site preparation is a planned injury into the otherwise intact healthy bone (usually considered apt for implantation in ideal case).

Hence soon after the injury to the bone, starts the cascade of bone healing. We shall understand the physiology of bone healing before the healing around the implants.
