*4.1.2 Adaptation of bone mass to load (lamellar and parallel-fibered bone deposition*

From the second month onwards, the microscopic architecture shifts towards either the well-known lamellar bone. Lamellar bone consists of parallel packing of the collagen fibrils with alternating course gives it the highest ultimate strength. Talking about its growth pattern it merely grows by apposition on a preformed solid base unlike the woven bone. This apposition can occur on 3 surfaces that can provide a solid base, viz., woven bone formed in the first period of osseointegration, preexisting or pristine bone surface and the implant surface.

#### *4.1.3 Adaptation of bone structure to load (bone remodeling*

Bone remodeling characterizes the last stage of osseointegration beginning around third month. With an initial high activity, it slows down again to later continue for life. In cortical and cancellous bone, remodeling occurs in discrete units, often called a bone multicellular unit, as proposed by Frost [33]. Remodeling starts with osteoclastic resorption, followed by lamellar bone deposition.

#### *Growth Factors and Dental Implantology DOI: http://dx.doi.org/10.5772/intechopen.101082*

However, initially osseointegration was conceived differently. The debate started with Collins (1954) who stated "Although histologically inert, an implanted object never becomes incorporated into the bone". Later in 1970 Southam et al. came up with their ideology that "When any metallic appliance is implanted in bone, a layer of fibrous tissue will always develop around the appliance which subsequently will never be as secure in the bone as it was at the time it was implanted".

It was believed by some authors like Jacobs (1976, 1977), Muster & Champy (1978) that a direct contact between implant and bone is possible only when implant is made up of ceramic. However, many researches done on implant biomaterial advocate use of various materials for osseointegration like stainless steel (Linder & Lundskog 1975), vitaltium (Klawitter & Weinstein 1974, Linder & Lundskog 1975, Weiss 1977), tantalum (Grundschober et al. 1980) and titanium (Branemark et al. 1969, 1977, Linder & Lundskog 1975, Karagianes et al. 1976, Schroeder et al. 1976, Juillerat & Kuffer 1977).

The point to note here is that titanium on contact with atmosphere instantaneously develops an oxide layer of about 100 A**°** thickness [TiO, Ti02, Ti,03 and Ti,O], thereby preventing a direct contact between bone and metal.

To further dissect the ultrastructure of the tissue adherent to the bone and implant in Osseo integrated implants, T. Albrektsson [34] investigated the interface zone between bone and implant using X-rays, SEM, TEM and histology.

Thirty-eight stable and integrated implants implanted in maxilla, mandible and temporal regions were removed for various reasons from 18 patients. The SEM study showed a dense adherent network of collagen fibers between titanium and bone. The pattern of the anchorage of collagen filaments to titanium appeared to be similar to that of Sharpey's fibers to bone. No wear products of titanium were seen in the bone or soft tissues in spite of implant loading times up to 90 months. The soft tissues were also closely adhered to the titanium implant, thereby forming a biological seal, preventing microorganism infiltration along the implant. This caused no adverse tissue effects. An intact bone-implant interface was analyzed by TEM, revealing a direct bone-to implant interface contact also at the electron microscopic level, thereby suggesting the possibility of a direct chemical bonding between bone and titanium.

#### **4.2 Osseointegration in compromised cases**

Any surgery on a human body requires a thorough understanding of the procedure as well as the systemic condition of the patient. Many times, we have encountered patients willing for an implant surgery with a compromised medical history. Researchers have always tried to find answers to.

Documentations of a comparative study by Moy et al. [35] done to evaluate the success and failure rate of dental implants on patients suffering with and without various risk factors, such as smoking, coronary artery disease, asthma, chronic steroid use, chemotherapy, head and neck radiation, diabetes, hypertension, and postmenopausal status suggest absence of any statistically significant difference between the two groups. However, when in the same study specific medical risk were evaluated, patient suffering from diabetes, history of head and neck irradiation and people with tobacco use showed significant increase in implant failure.

#### *4.2.1 Diabetes mellitus*

Diabetes mellitus impairs/delays normal healing hence plays a direct role on implant success rate. Thus, it has been mentioned as a relative contraindication to implant placement. Olson et al. [36] found that duration of diabetes and implant length were statistically significant predictors of implant failure. Diabetic patients face problems of delayed wound healing, increase in micro vascular and macro vascular disease, impaired response to infection, and susceptibility to periodontal disease.

In animal models, growth factors with vascular properties have been used by Kawaguchi [37] to evaluate wound healing. He reported that" rhbFGF shows to improve fracture healing in normal rats and rats with diabetes, facilitating the repair process in normal rats and improving the impaired healing ability in rats with diabetes". bFGF also has shown increased angiogenesis, decreased wound complications, and improved bone mineral density in rat healing sternal wounds [38]. It can be comprehended by this that angiogenic and osteoinductive properties of growth factors improve bony and soft-tissue wound healing thus playing an important role in patients with diabetes.

#### *4.2.2 Head and neck radiation*

Patients are living a longer and a good quality life after cancer resection surgeries and consequent rehabilitation. Prosthesis plays a major role for these patients in uplifting their confidence of self-image. Dental implants have served to improve the success of these prostheses compromising oral and facial structures.

Radiation has many deleterious effects, the most relevant to bony and soft-tissue healing being hypocellularity, hypovascularity, and hypoxemia. Thus, increasing the failure rate during the osteophyllic or osteoconductive phases of osseointegration.

Before beginning with application on human beings, growth factors loaded on suitable carriers are inserted in animals to delineate their effects in all possible conditions. One such study evaluated the effect of BMP-2 on irradiated and non-irradiated rabbits. The irradiation dose was 20 Gy of 6-MeV electron beams. After irradiation, hydroxyapatite discs coated with rBMP-2 were applied subperiosteally in the snout area. Histological analysis demonstrated that rBMP-2 was equally effective in bone formation in irradiated and non-irradiated tissue [39]. Two other studies also found improved bone regeneration after treatment with BMP-2 or BMP-3 in animal cranial bone defects.

Recent studies reveal a marked reduction in TGF- ß, PDGF, and bFGF expression in cortical and cancellous bones post radiation up to range of 60-70Gy. (T.L. Aghaloo et al., unpublished data). Local TGF- ß administration may overcome radiationinduced impaired wound healing by increasing wound breaking strength, possibly via an increase in the synthesis of type I collagen by fibroblasts.

Another study evaluated the effect of grafting material that was pretreated with bFGF. It was found to cause induction of angiogenesis and osseous healing of irradiated mandibular resection sites. Also active bone formation and re-establishment of mandibular contours occurred in the bFGF-treated rabbits, but control animals experienced sequestration, necrosis, and failure to heal [40].

#### *4.2.3 Smoking*

Smoking has shown a large role in peri-implant bone loss. This is attributed to the carbon monoxide; oxidating radicals, nitrosamines, and nicotine that are released during smoking. This nicotine plays havoc in the system of an individual. It causes a systemic increase in epinephrine and norepinephrine thereby decreasing blood flow,

increasing platelet aggregation, causing polymorphonuclear lymphocyte dysfunction, and increasing fibrinogen, hemoglobin, and thus blood viscosity.

Nicotine also causes local vasoconstriction from direct absorption into oral mucous membrane. This delays the wound healing. The effect of growth factors VEGF, bFGF, and BMP-2, −4, and − 6 gene expression is significantly inhibited, leading to suppression of bone healing and vascularity [41].

In animal studies, osteoinductive bovine bone protein plus autogenous bone grafting completely overcomes the inhibitory effect of nicotine [42].
