Current Advancements in Bone Regeneration - An Overview

Introduction:

The skeletal system is the primary stress-bearing system. This rigid structure of the body performs various functions, such as supporting the body and giving it a structure, producing blood cells (red and white), facilitating movement, storing minerals, protecting organs, etc.

How Does Bone Appear Microscopically?

The bone, although it looks like a rigid and static structure, the microscopy paints a different albeit exciting picture. Microscopy of the bone shows a complex network of canals supplied by their nutrient arteries, cells, and marrow.

What Are the Cells Present In Bone?

The bone consists of four main types of cells, namely:

• Osteoprogenitor Cells: These are neural crest cells that have not yet been differentiated into the following types of cells. They may become any other type of cell, depending on internal and external factors.

• Osteoblasts: These are the bone-forming cells. They are responsible for depositing the uncalcified bone matrix, also known as osteoid. This osteoid, when calcified, becomes the rigid bone.

• Osteocytes: These are osteoblasts that become entrapped within the deposition of the osteoid matrix and later get calcified. They consist of microscopic projections or processes used to draw nutrition to sustain themselves.

• Osteoclasts: These are multinucleated giant cells responsible for the resorption or eating away of the bone. The osteoclasts and osteoblasts maintain a dynamic balance between bone formation and bone destruction.

What Is Bone Marrow?

The marrow is the soft material present within the bone. The national dictionary of cancer terms defines it as the soft, spongy tissue that has many blood vessels and is found in the center of most bones.

The bone marrow is of two types, namely, red and yellow.

• The red marrow contains blood stem cells that can become red blood cells, white blood cells, or platelets.

• The yellow marrow contains fat and stem cells that differentiate into cartilage, fat, or bone cells.

What Is Bone Regeneration?

Bone regeneration is a physiological process of bone, which can be seen during routine fracture healing. Although the bone is involved in continuous remodeling throughout adult life, there are conditions in which bone regeneration is required in large quantities. In skeletal reconstructions of significant bone defects created by trauma, infection, tumor resection, and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions, and osteoporosis.

There are many strategies to augment the impaired or insufficient bone-regeneration function, including the gold standard autologous bone graft, free fibula vascularized graft, allograft implantation, and growth factors osteoconductive scaffolds, osteoprogenitor cells, and distraction osteogenesis. Improved local strategies in terms of tissue engineering and gene therapy, or even systemic enhancement of bone repair, are under intense investigation to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to the normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis.

What Does A Successful Bone Regeneration or Reconstruction Require?

Successful bone reconstruction requires bone production, osteoinduction, osteoconduction, mechanical stimulation, and vascularisation. Besides, drugs that act in bone metabolism can play an essential role in bone growth. Autogenous cancellous bone graft is currently the gold-standard treatment of bone loss for several reasons, including the osteogenic, osteoconductive, and osteoinductive properties of autograft and the lack of disease transmission or immunogenicity when utilized.

What Are the Limitations of the Gold Standard Material Currently In Use?

The significant drawbacks of autologous bone, which, as mentioned earlier, is currently the golden standard for bone regeneration procedures. They are as follows;

• Limited availability and variable quality.

• Hematoma (bruise).

• Infection.

• Increased operative time.

• Bleeding.

• Chronic pain at the donor site.

• Additional costs.

How Are the Limitations of Autologous Grafts Being Addressed Currently?

Because of the limits mentioned above, there is an expanding need for bone reconstruction paired with the growth of interest in the discipline of bone substitutes and tissue engineering. Tissue engineering in bone reconstruction includes utilizing growth factors, scaffolds, and mesenchymal stem cells. Synthetic scaffolds mimic the physical and mechanical nature of native tissue and promote osteoconduction for bone regeneration. These graft substitutes, biomaterials, or matrices, are formed from a variety of materials designed to mimic the three-dimensional characteristic of autograft tissue while also providing the ability to sustain cell proliferation onto the construct.

What Are the Scaffolding Materials Currently in Use?

1. Human Tissue-Derived Scaffolds: These are homologous cancellous bone and demineralized bone matrix. The organic matrix of bone is a scaffold or delivery system for bone morphogenetic protein. DBM may be generated by the acid extraction of processed allograft bone and is available in several forms, including freeze-dried powder, granules, gel, putty, and strips. The advantage of these materials is their good biocompatibility and bioresorbable properties. Disadvantages, however, are the natural source, processing, possible disease transmission, and immunogenicity.

2. Biomaterials: These are synthetic graft substitutes, or matrices, formed from a variety of materials, including natural and synthetic polymers, ceramics, metallics, and composites, that are designed to mimic the three-dimensional characteristics of autograft tissue while maintaining viable cell populations.

What Are the Ideal Requisites for Synthetic Biomaterials?

1. The surface should permit cell adhesion, promote cell growth, and allow the retention of differentiated cell functions.

2. The scaffolds should be biocompatible, lacking an immunogenic response. Neither the polymer nor its degradation by-products should provoke inflammation or toxicity in vivo.

3. The scaffold should be biodegradable and eventually eliminated unless metallic.

4. The porosity of the material should be high enough to-

• Provide sufficient space for cell adhesion.

• Extracellular matrix regeneration

• Minimal diffusional constraints during culture.

• The pore structure should allow even spatial cell distribution throughout the scaffold to facilitate homogeneous tissue formation.

• The scaffold structures must be highly porous, open-pored, and fully interconnected.

• The material should be reproducibly processable into a three-dimensional structure.

How Does A Synthetic Biomaterial Respond to Load and Stress?

Bone responds to the absence and presence of physical load. In response to these loads, the body either resorbs or forms bone. Given this principle, it is crucial to design a matrix that possesses mechanical properties similar to the tissue in the immediate surrounding area of the defect. An over-engineered matrix may result in bone resorption around the implant site, while an under-engineered matrix may fail as mechanical support to the skeleton.

How Does A Synthetic Biomaterial Act?

Several three-dimensional porous scaffolds fabricated from various biodegradable materials have been developed and used for tissue engineering of bone tissue. Synthetic bone-graft substitutes produced to overcome the inherent limitations of autograft and allograft represent an alternative strategy. Biomaterials are temporary matrices for bone growth and provide a specific environment and architecture for tissue development.

In addition, scaffolds can be used as a vehicle for drug delivery, such as antibiotics, chemotherapeutic agents, or growth factors.

• Polymer.

• Ceramic.

• Metallic.

• Composite.

Conclusion:

Thus bone regeneration is a complex biological process that, when impaired, has led to the field of tissue engineering, stem cell research, and the development of synthetic materials that can aid in guided bone regeneration.