The basic unit of bone is an osteon, which is made up of concentric lamellae of compact bone surrounded by a Haversian canal. There are two components to bone, cortical and trabecular. Cortical bone is dense and surrounds the marrow space, making up 80% of the skeleton. Trabecular or cancellous bone consists of plates and rods which are arranged in a honeycomb like interconnected network and interspersed …show more content…
within the bone marrow. [2]
Bone formation and remodelling takes approximately 4 to 6 months and is primarily facilitated by its cellular units; osteoblasts, osteoclasts, osteocytes. Osteogenesis is the process of new bone formation by osteoblasts, which are polarised, mononuclear cells originating from mesenchymal osteoprogenitor cells. They are responsible for producing bone collagen, proteins, and the regulation of osteoclasts. They also express pro-osteogenic agents such as osteocalcin.[3]
Osteoclasts are large, multinuclear cells that are derived from haematopoietic progenitor cells. They are involved in the degradation and resorption of bone matrix and mineral. Osteoclast activity is regulated through osteoprotegrin and calcitonin.
Osteocytes are mature osteoblasts that line the bone surface or become embedded in bone matrix pits called lacunae. They form the majority of bone and act as mechano-sensors, converting mechanical loading stimulus into biochemical signals and play a critical role in maintaining the balance of osteoblast activity. Osteocytes are also capable of intercellular signalling through cytoplasmic extensions within the canalicular network. [1, 2]
Osteoinduction is the process by which mesenchymal stem cells and osteoprogenitor cells are induced by signalling and gene expression factors such as bone morphogenetic proteins to differentiate into osteoblasts.
Osteoconduction is the physical ability of a bone graft to allow bone cell attachment and proliferation on its surface, acting as a scaffold for bone healing.
[4]
1.2 Bone Grafting
Bone grafting is the procedure of using bone tissue to repair, restore, and remodel bone that may have been lost due to disease or trauma. A bone graft, however, does not need to be made only from human derived bone tissue. It is defined as any implanted material that promotes bone healing through osteogenesis, osteoinduction, or osteoconduction, by itself or when used in conjunction with other materials. [5, 6]
Bone grafts can be sorted into several categories; autografts, allografts, xenografts, synthetic grafts, and tissue engineered grafts. Each have their own distinct advantages and disadvantages and their application depends on factors such as defect size, shape, viability, handling, resorption rate, bioactive properties, composition, biomechanical properties, side effects, ethical issues, and cost. [5]
Clinically, bone grafts are mostly used as a means of fracture fixation, especially in spinal fusion, dental implant, and joint replacement surgery such as total knee and hip replacement surgery.
1.3 …show more content…
Autografts
Autografts are generally regarded by the orthopaedic community to be the gold standard in treatments involving bone grafts. An autograft is bone tissue sourced from the patient themselves and transplanted to the required site. They are considered to be ideal because of their histo-compatibility, abundance in viable osteogenic cells, and an osteoconductive bone matrix with growth factors. The bone tissue for autografts can be harvested from non-essential bones, such as the chin, mandible, ribs, fibula or more commonly, the iliac crest. [7] Autografts can be cortical, cancellous, or cortico-cancellous. Cortical grafts are mainly osteoconductive and provide immediate mechanical support to the surrounding tissue while cancellous grafts offer greater osteoinductive properties but poor immediate mechanical support, taking up to a year to reach the same strength as a cortical graft. (Redacted)
The main disadvantages of autografts stem from the issue of pain and morbidity associated with the donor site, which could pose further risks such as fractures, hematomas, infections or neurovascular injury. It is also harder to perform in paediatric patients due to the increased likelihood of fractures or other complications. [7]
1.4 Allografts
Allografts or banked bone are bone tissue obtained from living donors, commonly from total hip replacement recipients, or alternatively, human cadavers. Like autografts, allografts can also be cortical, cancellous, or cortico-cancellous. Allografts’ main advantage stems from their ready availability in various shapes and sizes, and can be processed as mineralised or demineralised and they also don’t carry a morbidity risk to donor sites. [5, 7]
Allografts have a great number of disadvantages, mostly due to their potential to elicit a graft-vs-host immune response within the recipient patient. Also, due to the increased risk of infection, allografts require sterilisation through gamma irradiation, which leads to poor biomechanical strength and degradation of proteins. Hence, the allogenic bone tissue is mostly osteoconductive but not very osteoinductive due to the lack of viability in growth factors and proteins, lost during sterilisation. [6]
1.5 Xenografts
Xenografts are any bone tissue sourced from non human biological sources, often coral, bovine or porcine. Xenografts offer a low cost, high availability option to bone grafting with good osteoconductive properties. They are also easily stored, usually distributed as a calcified matrix.
Infections and zoonotic diseases are a major concern with xenografts and similar to allografts, xenografts lose most of their osteogenic and osteoinductive properties during the sterilisation process. Clinically, xenografts have performed well in dentistry but poorly in orthopaedic applications. [6]
1.6 Synthetic Bone Graft Substitutes
There are an evergrowing number of bone graft substitutes that aim to provide readily available alternatives to bone tissue. They’re produced in most shapes and sizes, such as chips, ganules, putty and injectable paste. Common materials include ion-substituted bioceramics, calcuim phosphate and calcium sulphate cements, and polymer-based bone graft substitutes. 1.2 Clinical Need
There is a significant need in the orthopaedic industry for improvements to bone healing and fracture management. Each year, hip, knee, and vertebral fractures costs the US health industry over $30 billion [8]. Of the 3 million orthopaedic surgical procedures performed annually, about 1.5 million in the US and 2.2 million worldwide involves bone grafting in some form as a method of repairing bone defects, facilitating implant fixation, and enhancing the regeneration procedure [5, 9]. After blood transfusions, bone is the second most frequent tissue to be transplanted [7].
About 480,000 spinal fusions are performed in the US each year and an estimated 5-35% of patients experience impaired healing post-surgery, causing pseudoarthrosis or non-union of bone. Joint replacements, primarily, hip and knee, also present a large proportion, with almost 750,000 surgeries being performed in the US and 1.2 million worldwide. Of these, 10% of joint replacements undergo revision surgery, with a majority being caused due to mechanical loosening and osteolysis [5, 10].
As life expectancy increases, it is expected that there will be a greater need for solutions to the current problems facing bone grafts. Although autografts remain as the ideal gold standard graft in terms of their biomechanical properties, bone growth factors, and low risk of adverse reaction, due to their associated site morbidity, there exists a niche in bone graft engineering to produce bone substitutes that mimic natural grafts.
Section 2: Bone Graft Engineering - Recent Advances
2.1 Bone Graft Harvesting
Studies into various harvesting methods show that autografts behave differently depending on the way they have been harvested.
It is thought that the technique used to harvest grafts affects the number, activity, and viability of transplanted bone tissue. Experiments conducted on pig mandibles compared bone milling, bone drilling, bone scraping, and piezo surgery techniques. The results showed that cell viability and growth factor expression of bone morphogenetic proteins and vascular endothelial growth factors were higher in the bone milling and bone scraping samples compared to bone drilling and piezosurgery
techniques.[11]
To minimise the pain caused during the harvesting of bone from the anterior iliac crest, an analgesia block is being studied to lower patient pain. The iliac crest receives innervation from the L1 nerve root and a transversalis fascia plane block through ropivacaine and epinephrine is suggested to lower patient pain and possibly the use of opioids in the post-operative period. The identification of the nerve root is guided by ultrasound for precise delivery of the analgesia block. [12]
When the iliac crest is unavailable for harvesting due to medical reasons such as osteomyelitis or other localised diseases, alternative sites and methods must be considered.
A possible solution to the associated morbidity of autografts is the method of harvesting graft through mesenchymal bone marrow aspiration, which is a percutaneous procedure. This could theoretically solve problems of increased operation time, loss of blood, pain, infection or nerve injury. A comparative study of bone marrow aspiration versus traditional iliac crest graft showed that the bone marrow aspiration significantly lowered the number and severity of complications such as anaemia, post-operative pain, and neuralgia by a factor of 10. [13]
In recent times, procuring bone graft from the calvarial bone has gained traction due to its easy accessibility and decreased patient pain perceptibility. Although the calvarium mainly consists of cortical bone, the use of bone scraping milling and oscillating saws allow for harvesting copious amount of cancellous like bone. This source of bone graft is suggested by a prospective study to be a readily available source for intraoral augmentation procedures involving the maxilla or mandible. [14] [15]
The reamer-irrigator-aspirator is a system that is increasingly being used to harvest bone graft and works by extracting through the bone marrow cavity using irrigation and suctioning during the reaming process. The bone obtained via this procedure is comparable to grafts obtained from the iliac crest and suitable for spinal fusion surgery. This system lowers the complication and morbidity rate by 13% when compared with traditional methods of bone grafting. [16]
The proximal tibia is also being considered as a possible alternative source of autograft. Experimental studies on the biomechanical stability and volume of bone graft accessed show that grafting through the lateral approach with a circular osteotomy is a viable option, leading to lowered morbidity without compromising the mechanical loading properties of the tibial bone