Bone healing after implantation

A successful implantation process is complete when the implant is safely secured to the bone, and functioning within the bone framework. In the past a special bone cement was used to “glue” the implant to the bone [1]; however, presently implants are manufactured in a way that allows the host bone to heal around the implant, securing it to its place [2]. This process is called “osseointegration”, or bone bonding [3].

Bones are constantly remodeling, meaning that the bone disassembles and re-builds itself; therefore, the surface of the implant must have certain surface topographies, containing pores and complex 3D characteristics, for the bone to bond to the implant surface [2]. This results in implant integration.
This is a short summary of the peri-implant bone healing process:

Primary implant fixation:

In order to ensure proper healing, the implant must be securely fixed to the host bone, allowing bone formation without causing too much movement [4,5]. Just as in the case of a fracture, wherein movement between broken edges of the fractured bone may impede the healing process [6-8], osseointegration is inhibited when the implant is not properly secured to the bone [9]. There is a delicate balance to implant placement, however, because a certain degree of space is required between the implant and the host bone in order for the bone to form properly [10,11].

Blood-implant contact:

The implantation process begins with a surgical procedure, which leads to a hemorrhage from the soft tissues surrounding the bone and ultimately, to the formation of a hematoma. The contact of blood and the foreign object – the implant – results in a variety of biological processes, such as inflammation, coagulation, and tissue formation, which are influenced by the surface chemistry and topography of the implant [12]. These processes create a monolayer of proteins, such as fibronectin and vitronectin, which can attach to the surface of the implant and interact with it, if the topography and chemistry of the implant are conducive to acceptance by the body [13,14]. These interactions between the implant and the proteinous monolayer create the basis for osseointegration and ossification (bone formation), and are crucial to proper healing of the wound and, ultimately, successful implantation.

Platelet activation and coagulation:

The first step towards healing is blood coagulation around the implant, which is controlled by the platelets [15]. Platelets are small cells that are activated by foreign objects, injured tissues, or signals released from other cells. Upon activation, the platelets secrete various molecules that interact with coagulation factors and begin the coagulation process [16] and express adhesion receptors that enable platelet-implant interaction [17]. These processes result in the formation of a clot [18, which will provide the conditions necessary for osteoconduction (recruitment of bone cells) [19]. The variety of cytokines, growth factors, and chemoattractants the clot contains encourage cell migration and adhesion [20-22].

The surface topography, as mentioned earlier, is one of the key factors in the success of these initial stages of bone formation. Studies have shown that roughened implant surfaces with nano-and-micro-topography display better activation than smooth surfaces [23]. Considering the importance of the clot formation to the migration of cells towards the implant and to the inflammation and osteoconduction processes, it is easy to understand why the surface topography and chemistry can have a great influence on successful healing [24,25].

Inflammation and angiogenesis:

The inflammatory response begins immediately following activation of the platelets and the coagulation process [16]. Immune cells arrive to the transplant area and trigger the release of cytokines [26]. These cytokines encourage inflammation, and appear to contribute to bone formation by inducing recruitment or maturation of bone cells [27]. Apart from the cytokines, another family of factors, called tissue growth factors β (TGF- β), are secreted; these factors further promote the formation on new bone, and improve healing of fractures and implantation wounds [28-33].
Bone cells, like all body cells, require consistent blood supply; therefore, angiogenesis (formation of new blood vessels) is crucial to the implant process, and angiogenic factors, such as VEGF, are secreted to induce new blood vessel growth [34-36].

The result of the inflammatory and engionenic processes is attraction and activation of bone cells, thereby creating the conditions needed for the formation of new bone around the implant.

Bone formation:

Attracted by the signaling molecules secreted in the area of the wound, mesenchimal cells arrive and differentiate into bone-building cells (osteoblasts) that begin to secrete matrix [37,38]. This matrix serves as cement, as well as a site for mineralization [39-41], so a calcified layer can be formed on the implant surface. This layer grows and expands, and the immature bone is then formed toward the implant and the surrounding tissues [42]. The growing immature bone also provides additional support to the implant [43]. After the wound is healed, the primary layer of bone on the implant surface dies and is absorbed, and the implant is anchored by bonding to the mature bone and the implant surface. If the implant surface features multi-dimensional complex topography then the bone can easily integrate into its surface, as opposed to smooth surfaces, where the bone simply grows around the implant [44]. If successful, the bone formation process ends with a strong fixation of the implant to the bone.

In summary, implantation triggers a cascade of events, starting with the formation of a hematoma, secretion of various factors, activation of platelets, and clot formation. This is followed by the arrival of immune cells, which induce inflammation. Later on, angiogenesis occurs, blood vessels grow toward the implant, and bone cells become mature and begin building the new bone. This results in a primary, immature bone formation on the implant surface, which is later on replaced by a mature bone. When the process is completed successfully, the implant is securely fixed in the host bone and functions as a natural extension of it.

References:

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