Materials for Surgery

A material for surgery is a material used to fill bone defects resulting from the surgical removal of bone cancer.

Materials for surgery includes transplant materials (bone grafts), biological materials, and synthetic bone substitutes.

1.4.1.1 Transplant Materials (Bone Grafts)

Bone grafting is a surgical procedure that uses transplanted bone to repair and rebuild diseased or damaged bones [65].

Osteogenesis, osteoinduction, osteoconduction and osteointegration are the four most important characteristics that a bone graft should have [66].

Osteogenesis is the formation of new bone beginning with osteoprogenitor cells that are in the graft, which survive the transplant, proliferate and differentiate into osteoblasts and eventually to osteocytes [67].

Osteoinduction is the stimulation and the recruitment of nearby undifferentiated mesenchymal stem cells to the graft site, which differentiate into chondrocytes and osteoblasts [68]. This process is mediated by a signaling cascade and the activations of some intra and extracellular receptors, the most important of which are part of the TGF-beta superfamily [68].

Osteoconduction is the ability to allow the growth of vascular tissue and the creation of a new Haversian systems into the architecture of the graft material [66].

Osteointegration is the connection between the host bone and the graft material without an intervening layer of fibrous tissue [69].

The three kinds of bone graft are autograft, allograft and xenograft (Figure 14).

Figure 14: Bone grafts: (a) Cortical strut autograft from fibula in a proximal humeral non-union treated by ORIF [63]. (b) Allograft got from a banked femoral head [63]. (c) Acetabular bone defect filled with bovine bone xenograft in chips [63].

Autograft is considered the gold standard of bone grafting because it exhibits all of the four desired characteristics mentioned above (osteogenesis, osteoinduction, osteoconduction and osteointegration [67], [66]), and elicits no immune response in the patient (Figure 14a).

It consists in using the bone obtained from the same patient receiving the graft. The bone is usually taken from non-essential bones such as the iliac crest, the fibula, the ribs [63].

However, autograft bone has also some disadvantages related to the morbidity at the donor site and the availability of the tissue. The operation could led post-operative pain and complications including creation of hematoma, blood loss, nerve damage, infection, arterial damage, fracture, aesthetic deformity [67].

Allograft is the most used bone substitute (Figure 14b). It is a graft picked up from a member of the same species as the host but genetically different [66].

It is taken from either living donors or nonliving donors and it is handled in a bone bank [63].

It can be used fresh, frozen, freeze-dried, mineralized and demineralized [66].

The cortical bone is prepared in the form of chips, granules and wedges, while the cancellous bone is in the form of powder [66].

Allograft poses the risk of transmitting viral diseases, but it is almost eliminated through tissue processing and sterilization. However, with these treatments, graft’s mechanical and biological properties are weakened [67].

Allograft is osteconductive and slightly osteoinductive, but it has not osteogenic characteristics because tissue processing reduces the host’s immune response and consequently there are not viable cells to donate osteogenic qualities [63], [67].

Xenograft is collected from a genetically different species than the host (Figure 14c) [66].

Bovine bone is the most used xenograft [66]. The bone is lyophilized, or demineralized and deproteinized, and then distributed as a calcified matrix [63].

Another common xenograft is coralline hydroxyapatite, which is generated from ocean coral [66].

Initially it is mainly composed of calcium carbonate, then it is processed to remove most of the organic content, and finally a calcium phosphate skeleton is achieved [66].

Others xenografts used are chitosan, gusuibu and red algae [66].

1.4.1.2 Biological Materials

Biological graft materials include demineralized bone matrix and collagen (Figure 15).

Figure 15: (a) Demineralized bone matrix [63]. (b) Collagen [70].

Demineralized bone matrix (DBM) is obtained by decalcification of the cortical bone, which is processed to reduce the infection potential and immunogenic response of the host (Figure 15a) [67].

The DBM retains the trabecular structure of the original tissue, and acts as an osteoconductive scaffold despite the removal of the mineral phase caused a decrease in structural strength [67].

DBM is more osteoinductive than allograft because growth factors are more available. However, DBM is more used as a bone graft extender than as a bone graft substitute [67].

Collagen promotes mineral deposition, vascular ingrowth, and growth factor binding, offering a favour environment to bone regeneration (Figure 15b) [67]. However, collagen may lead potential immunogenicity and offers minimal structural support [67].

Collagen is not a valid graft material but, when coupled with bone morphogenetic proteins, osteoprogenitor precursors, or hydroxyapatite, it improves notably graft properties [67].

1.4.1.3 Synthetic Bone Substitutes

Synthetic bone substitutes are biocompatible and induce minimal fibrotic changes. They support new bone formation and undergo remodelling. In addition, they have similar toughness, modulus of elasticity, and compressive strength to that of the bone being replaced [66].

Synthetic bone substitutes are less painful, require less operating time, and lead to less blood loss than bone grafts [63].

They also have some disadvantages such as low resorption, difficulty in handling, and the possible development of an inflammatory reaction from a foreign body [67].

The most common synthetic bone substitutes are ceramics bone substitutes, calcium phosphate cements (CPCs), calcium sulphate (CS), synthetic polymers, bioactive glasses (BGs), and glass ionomer cements (Figure 16).

Figure 16: (a) Bone substitute of hydroxyapatite and tricalcium phosphate [71]. (b) CPCs [72]. (c) Calcium sulphate [73]. (d) Bone substitute containing PEG [74]. (e) Bioactive glass granules (BonAlive^®) [75]. (f) Glass ionomer cement [76].

Ceramics bone substitutes are calcium-based replacements, a blend of HA and tricalcium phosphate (TCP) (Figure 16a). HA is a mineral approximately inert that is maintained in vivo for long periods of time, while TCP, that is the HA amorphous phase, is biodegraded within 6 weeks of its implant [63]. HA has high mechanical strength, while TCP possesses poor mechanical qualities [63].

The most used ceramic bone substitute is a biphasic calcium phosphate that combines 60–40% HA with 40–60% TCP in order to achieve a balance regarding bone resorption and mechanical support [63]. For bone ingrowth, macroporosity of about 100–400 𝜇m and interconnected porosity are required [63]. HA-TCP are obtainable in form of blocks, granules, and injectable kits [63].

The main limit of ceramic bone substitutes is the strength, which varies between 10 and 60 MPa, and is much lower than the compression strength of the cortical bone, which, as already mentioned, is between 130 and 200 MPa [63].

Calcium phosphate cements are white powders, consisting of calcium phosphate, that when blended with a liquid, create a cement which can be modelled during surgery to adjust the silhouette of bone loss (Figure 16b). In 20 minutes, the cement hardens and forms nanocrystalline hydroxyapatite [63].

The cement is biocompatible, osteoconductive, and with time it is reabsorbed and replaced with new bone [63]. However, it is very fragile, so it is not used for load-bearing applications [63].

Calcium sulphate deserves to be mentioned, since it allows an adequate gap filler, provides for vascular ingrowth, and resorbs fast and totally (Figure 16c) [63].

Synthetic polymers are divided into degradable and non-degradable types. Degradable polymers have the double advantage of improving healing and being completely absorbed by the body [63].

The most used synthetic polymers are polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), and polyethylene glycol (PEG) (Figure 16d) [63].

Bioactive glasses are very beneficial materials since they generate both conductive and osteo-productive events [77]. Bioactive glasses are able to promote the growth of bone cells [78], and to bond strongly with hard and soft tissues [79], [80].

BGs, after being implanted, undergo specific reactions, leading to the formation of an amorphous calcium phosphate (ACP) or HA phase on the glass surface, which is responsible for their strong bonding with the surrounding tissue [80]. In addition, BGs release ions that activate expression of osteogenic genes [81], and foster angiogenesis [82].

The degradation rate of bioactive glass can be adjusted, by controlling the chemical composition of the glass, to match that of bone ingrowth and remodelling [83].

The structure and chemistry of BGs can be customized by changing either composition, or manufacturing technique [83].

For all these reasons, bioactive glasses are considered very promising materials as bone substitutes (Figure 16e). They will be discussed in more detail in Chapter 2.

Glass ionomer cements are composed of calcium/aluminium/fluorosilicate glass powders, blended with polycarboxylic acid to obtain a porous cement paste (Figure16f). The paste takes 5 minutes to harden, after which it is insoluble in water [67].

They have a compressive strength and modulus of elasticity similar to that of the cortical bone. They are biocompatible, and their porous structure promotes osteoconduction, and subsequently bone ingrowth. These cements aren’t resorbable, and therefore they aren’t replaced by bone [67].