INTRODUCTION:

Bone is generally defined as a rigid organ that constitutes the vertebrae and skeleton. Bone is usually stereotyped as just a scaffolding material which holds the body together. However, a bone is a dynamic organ that continually undergoes remodeling and reshaping to withstand and adapt the local loads. Moreover, bone stores essential nutrients, minerals, and lipids. Bone provides an environment for the bone marrow to produce blood cells that nourish the body and also play a vital role in protecting the body against infections. These functions make the 206 bones of the human body as an organ that is essential to our daily existence¹. During the first year of life, almost 100% of the skeleton is replaced with new bone, while in adulthood the rate is close to 10% per year.

Remodeling enables bone to adopt functionality changes in loading. Maximum bone mass value is reached in the 30's. Generally, the loss of bone mass is age, gender and race dependent. For example, 50% of bone mass is lost by 80s, which is more significant in males than females and in black's than whites. Women lose an estimated 35% of their cortical bone and 50% of cancellous bone with age while its 2/3 of it in men².

Typically, about 0.7% of the human skeleton is resorbed and replaced by new healthy bone each day. Therefore, the average turnover of the entire skeleton occurs approximately entirely 142 days². This process is usually called as bone modeling, and which involves independent uncoupled action of osteoblasts and osteoclasts. Hence, bone is resorbed in some regions and added in the other areas. The other factor which influences the bone modelling process is the movement of teeth/tooth during orthodontic treatment. During which, the bone resorption takes place in the direction of tooth movement and vice versa in the opposite direction. However, the bone modeling process slows down substantially at the end of the growth spurt. Bone modelling influences the size and shape of the bone^3-6.

Bone remodeling:

Bone remodeling is a systematic and sequential process. Unlike bone modeling, this remodeling process is a coupled action of both osteoblasts and osteoclasts, which does not change the size and shape of the bone. Figure 1 describes the various steps involved in bone dynamics.

Depending upon the porosities, bone can be classified as cortical or compact bone and cancellous or trabecular bone. The porosities of host bone marrow have blood vessels, nerves, and various cell types. Marrow space is red as long as it actively produces red blood cells or a reserve population of mesenchymal stem cells and turns yellow when ages and is converted into fat storage site. Marrow is a highly osteogenic material which stimulates bone formation if placed in an extracellular skeletal location as done in bone grafting in the dental area^3,4,7.

Figure 1: Stages involved in bone dynamics

Cancellous bone, in addition to porosities, differs from the cortical bone with well-defined nutrient connections called “Haversian canals”. These canals are connected at right angles to volksman canals which are similar in structure but smaller in diameter than Haversian canals. Haversian systems are concentric circles, and they do not join geometrically. They are joined by mature bones which are not organised into Haversian systems. Instead, they are organised with lamellar bone joined to the Haversian system by a cemental line, known as interstitial lamella. Hematopoietic marrow and stem cells reside in between interstitial lamella. Each trabecula is lined by endostealosteoblasts and contains osteoid and lamellar bone, some of which may be organised into Haversian systems. The importance of this knowledge is the recognition that mature bone is viable vascular and yet more mineral dense⁴.

Based on the microstructure, various types of bones are produced during healing. They include woven/phase 1 bone, composite bone, and lamellar bone. Woven/phase 1 is highly mineralised, stronger and plays a significant role in healing. However, Woven/phase-1 lacks the lamellar structure and does not last long. Composite bone is transition bone in healing and has woven lattice filled with lamellar bone. Lamellar bone is the most abundant, mature, load-bearing bone in the body. Lamellar bone forms slowly; however, it is well organised and extremely strong of all types. Bundle bone is primary bone found around ligaments, and joints and that consists of striated interconnections with ligaments⁴.

Bone Grafts:

The bone graft is a piece of bone that is obtained either from a natural or artificial source which is used to replace the missing bone. In other words, it is a material to retrieve the lost bone in the most acceptable, technical and skillful manner so that the form and function can be restored⁶.

Applications of Bone Grafts:

In orthopedics, bone grafts are widely used in spinal fusion surgeries, bone and joint tuberculosis, fracture repair, to fill a cavity formed by the bone tumour, patella reconstruction, pubis symphysis reconstruction, scoliosis correction, occipital cervical fusion, degenerative spine disease and craniotomy.

In addition, bone grafts are also widely used in dentistry for various bone-related treatments. They include; treatment of bone loss, treatment of bony defects in periodontics, developmental bony defects, hasten healing and restore bone contour as a consequence of surgery of benign cysts or tumours, for implants, pre-prosthetic surgical procedures where minimal amount of bone is a prerequisite, defects in alveolar ridge, trauma, infection and/or congenital malfunctions^8,9.

Bone grafts may be used to encourage the healing of un-united fractures, to spread union at osteotomy sites to restore the continuity of bone, to replace the excised segments of mandible or maxilla. Bone grafts can also be used as an onlay to restore the bone contour or to increase the thickness of the bone in areas of severe atrophy post-extraction. They may also be used in the bony defects; due to trauma or infection, that require to place implants in strategic sites for functional and esthetic success. They may also be responsible for speed healing to refill a peri-implant defect due to peri-implantitis, for horizontal or vertical augmentation of the mandible¹⁰.

Mechanisms of bone growth and the role of bone grafts:

Various Mechanisms of bone growth are Osteoconduction, Osteoinduction and Osteogenesis. Osteoconduction provides a matrix for new bone growth. Osteoinduction is where growth factors encourage mesenchymal cells to differentiate into osteostic lineages. Osteogenesis means transplanted osteoblasts and periosteal cells directly produce bone^11,12.

Irrespective of the type and amount of graft material incorporated, all the grafts undergo specific steps in common¹³.

Step 1- Hematoma formation (release of cytokines and growth factors)

Step 2- Inflammation (development of fibrovascular tissue)

Step 3- Vascular in growth (often extending Haversian canals)

Step 4- Focal resorption of the graft

Step 5- Intramembraneous and/or endochondreal bone formation on the graft surface.

Bone grafts are classified into two types, including bone-derived materials and non-osseous materials. The classification of bone grafts was detailed in figure 2.

Autografts:

Egosseos-coagulum, bone blend, bone swagging, bone harvested from posterior ilium, costochondral rib, cranium, mandibular block, tibia and microvascular free bone flaps are few examples of autografts^1,14-19.

The autografts form the bone either through osteoconduction, osteoinductive or by osteogenic effects. It has been observed that the rate of bone formation was increased when autografts were used in combination with platelet-rich plasma (PRP) or plasma rich fibrins (PRFs) or with bone morphogenic proteins (BMPs). In addition, the combination of bone grafts with BMPs also enhances the compatibility with the host bone^20,21. The shrinkage that is observed after placing the graft is around 30% depending upon the defect and condition being used. The advantages associated with autografts include, they contain viable osteoblasts, provide additional surface for the interaction of cellular and vascular elements, no associated graft rejection or integration or both of placed graft takes place. The disadvantages of autografts are they require additional surgical site leading to pain and soreness, large defects cannot be covered, poor surgical visibility (osseous coagulum) and technically difficult (bone swaging)^6,9,11,19.

Allografts:

Examples of allografts include DFDBA (Demineralised freezed dried bone allograft), FDBA (freezed dried bone allograft). The bone formation is both by osteoinduction and osteoconduction. The various advancements which have been seen are FDBA in combination with autografts, injectable and mouldable forms, and blend of mineralised and demineralised allografts. These advancements have shown promising results. The graft rejection is due to the granulocyte’s interaction between the graft and host. Thus, marrow cells must be removed in order to enhance the compatibility of the graft with the host. The shrinkage observed is 30%. The advantages of allografts include, they are useful in filling large defects, they can be stored and used later and no requirement of the second surgical site. The disadvantages include, they require compatible donor, sophisticated lab procedures, the possibility of disease transmission, antigenicity and immunological reactions^{1,6,9,11,12,19}.

Figure 2: Classification of Bone grafts

Xenografts:

Examples of xenografts are Kiel bone, calf bone, and corals.

The bone formation is generally via osteoconduction, but the potential is low. Hence, various attempts have been made to increase the possibility of bone formation. They are autogenous spongia in combination with bovine-derived bone, autogenous bone combined with deproteinised bovine bone, bovine-derived hydroxyapatite (HA) with cell binding polypeptide. Like in allografts, the xenograft and the host compatibility can be enhanced by the removal of marrow cells from the graft. The xenografts are useful in filling large defects, they are readily available, and require no other morbidity site. However, placement of xenografts needs elaborated lab procedures; they show immunological reactions and have more ethical issues^{1,6,9,11,12,19}.

Alloplast:

Examples of alloplasts arehydroxyapatite crystals, tricalcium phosphate, and bioactive glass.

The new bone formation is through osteoconduction. The various modifications are continuing for better results with porous ceramic composite grafts, tri-calcium phosphate, biphasic calcium phosphate, implant bone grafts are few to mention. The alloplasts show excellent tissue compatibility, and they do not elicit any inflammation, large defects can be filled using them, and also require no second surgical site. However, they are less potential for host bone regeneration and require elaborated lab procedures^{1,6,9,11,12,19}.

Choice and selection of the bone grafts:

The choice and the selection of the bone grafts are solely by the dentist/surgeon. However, it will be wise to consider the patients’ choice as the people in most of the countries are with diversified religious beliefs, ethical practices and people with compellingly different opinions and theories. For example, a Hindu orthodox priest may not agree for a bovine-derived material to be inserted into his body. Similarly, a Muslim priest may not accept a porcine-derived material, and also a Jain would never allow an animal-derived material from being used upon him/her. The choice and selection of bone grafts depend not only on religious beliefs but also depends on individual decisions. Some Females may not like an animal to be sacrificed for fulfilling their needs, while some may be particular the animal isn't harmed, while some accept it only if their dentist/surgeon suggests it to be the best for them. Hence, patients’ opinions even have to be taken care of before the procedure is carried out^2,20-22.

Methods to assess the success of the bone grafts:

Assessment is one of the most exciting and crucial aspects to the clinician as it decide the success of the grafts, and that is usually done by a non-invasive method. Hence, clinicians cannot differentiate between the necrotic bone, viable bone graft and cortical bone. Newer modalities like Densitometric assessment of x-ray film, arteriograms are complementary to a conventional radiograph. Other advanced modalities like Technetium bone scans, which depends on graft revascularisation (a basic sign of vital tissue) are more reliable. CT scans, 3-Dimensional reformatting technique, Biopsies and histological evaluation can be done if the site of graft is exposed surgically for other reasons are also frequently adopted. The experimental method of tetracycline labelled with fluorescent lightening has been used to access the viability of bone is promising but still not yet translated to clinics^23-27.

Newer technologies:

3-D bone printing using nanotechnology:

Engineers have developed 3-D printable ink that produces a synthetic bone implant that rapidly induces bone regeneration and growth. This hyperplastic bone material can be easily customised. The structure majorly is composed of hydroxyapatite yet hyper-plastic, robust and porous at the nano, micro and macro levels. The high concentration of HA creates an environment that induces rapid bone regeneration. Antibiotics and different growth factors can also be combined to avoid post-surgical infections and enhance bone growth respectively^28,29.

Tissue-engineered bone using autologous progenitor cells:

It is a process which enables one to establish a “mini bio-reactor” in a patient’s own body. This is done by inserting biodegradable polymer scaffolding material and BMPs introduced in the patient’s own body to attract the stem cells resulting in the generation of bone tissue in a few days. It may be possible in the near future that a physician will be able to inject the scaffolding material with ideal protein into the place where the bone growth is required or to be repaired. The advantages of this procedure include it requires less surgical time, more patient comfort and less surgical cost³⁰.

Engineered bone grafts:

Researchers have engineered living bone tissue to repair bone loss. The researchers seeded a scaffold with stem cells from the host, which were taken from the host's adipose tissue since it was easier and more practical to extract than marrow cells, and it also provided an adequate quantity of cells. This engineered tissue was later placed inside a bioreactor to grow for about three weeks. Thus, a bone graft was engineered and can be implanted in the area of interest^31-33.

Irrespective of the type of the graft, the perfect techniques and technology are used a little amount of graft shrinkage is observed. In this regard, an oversized graft is to be preferred to compensate this volumetric shrinkage. Embryologically similar origin areas have less shrinkage compared with non-embryologically similar origin³⁴. The shrinkage, even though embryologically similar, can also be seen if the contour is different. Cancellous cellular marrow grafts have less shrinkage than cortical grafts but don't have any structural stability. However, it can be compensated by using externally stabilised membranes^10,34. Each bone defect type has its healing characteristics, healing potential, and risk of complications^4,35. It is unlikely that a bone grafting material that is ideal for all indications will be identified³⁵.

CONCLUSION:

Thus, bone grafting is a procedure to replace and/or regenerate what is lost due to various reasons such as trauma, long span edentulous area, fractures, periodontal problems and many more. Among all the grafts available, autografts are considered to be the gold standard. The main advantage of this graft is the absence of graft rejection, reduced risk of disease transmission and better bone formation. The main disadvantage is the second surgical site. Many at times, the second surgical site requires a longer time to heal, and even soreness is observed. Stereotypic thought of graft rejection due to B or T lymphocytes is wrong; rather, it is due to the interaction between the granulocytes of graft and host tissue. The current research is focused on alloplast as it seems to provide promising outcomes. Furthermore, it also solves the maximum disadvantages associated with autografts. The research is still ongoing, and the advancements such as growth factor encapsulation, implantable bone graft materials, porous ceramic composite bone graft and polymeric filler defects are worth mentioning. However, the success of the grafting procedure depends upon the type of defect, the type of graft, the site where it is placed, aseptic conditions, and the skill of the clinician. It also depends upon the individual’s general health, habits, maintenance etc. Thus, we can say that bone grafts are a solution to replenish what is lost.

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Received on 12.06.2019 Modified on 19.12.2019

Research J. Pharm. and Tech. 2021; 14(11):6101-6105.

DOI: 10.52711/0974-360X.2021.01060