Synthetic Bone Fillers and Substitutes


skeleton

Hydroxyapatite

The prototypical bioceramic is hydroxyapatite, a hydrated calcium phosphate similar in crystalline structure to the mineral component of bone. The material is produced by treating a common form of marine coral in a chemical process that converts the coral to hydroxyapatite. The porous, interconnected structure of the coral remains intact, providing an ideal matrix through which new bone tissue can grow. One coral head weighing 150 to 200 pounds provides enough material for hundreds of bone grafts.

Scientists have also developed a droplet-based microfluidic technology to formulate consistent, dense hydroxyapatite nanoparticles that can effectively mimic the functions of bone material in their natural biological systems, providing unique microstructures with very high surface areas and porosity.

The interconnected, porous structure is similar to the porosity of human bone. When placed in contact with viable bone the implant provides a strong natural foundation for new bone in-growth and offers structural support during the healing process. Upon healing, the composite of bone is comparable in strength to the surrounding bone. Hydroxyapatite is widely used for orthopedic, dental, and related biological applications. You sometimes see the type used called IP-CHA for interconnected porous hydroxyapatite. New bone cells and ceramic materials can deposit inside the pores.

A synthetic bone filler sold by Berkeley Advanced Materials is tailored for slow resorption; it is based on Tricalcium Phosphate (TCP) and Hydroxyapatite (HAP). The product (Bi-Ostetic) is formulated to enhance bone regeneration and promote bone in-growth. The compound is available either in granular form or as blocks. The spongy bioceramic granules resemble cancellous bone chips and the manufacturer says implants made from the material are radio-opaque and biocompatible.

Synthetic biodegradable polymers

Synthetic polymers have some advantages over natural materials. They can be designed and made to have desired physical properties (within limits). Properties of interest include glass transition temperature, thermal degradation temperature, density, and viscosity. Because they can be manufactured in controlled processes, they have predictable lot-to-lot uniformity and have fewer concerns regarding immunogenicity. As polymers made from fundamental chemical building blocks, they have simple and well known chemical structures and properties and can be made from reliable sources of raw material.

Aliphatic polymers were one of the first and continue to be the most frequently used group of materials in bone tissue engineering. This class includes poly(lactic acid) (aka poly lactic-co-glycolic acid), poly(glycolic acid) ), poly(lactic-coglycolide) as well as derived copolymers. Engineers call these materials “tunable”: the mechanical characteristics and the degradation profile can be affected by the type of processing technique. Solvent casting, particulate leaching, and compression molding are used to fabricate the polyglycolic acid based porous scaffolds. Its strength and modulus are very high (polyglycolic acid fibers are used to make sutures). Polylactic acid is prepared from the cyclic dimer of lactic acid that exists as two optical isomers: D & L- lactate is the naturally occurring isomer, and DL-lactide is the synthetic blend of D-lactide and L-lactide. The homopolymer L-lactide is a semi-crystalline polymer. This material has high tensile strength, elongation and modulus that make it more suitable for load-bearing applications such as sutures and orthopedic fixation. The homopolymers and related copolymers have multiple uses due to their good mechanical strength, degradation, biocompatibility. Engineers use polyglycolic acid in applications such as scaffolds for tissue engineering, mesh, and drug delivery.

Polypropylene fumarate (PPF) is useful because it can be injected into the body. Before cross-linking the pre-polymer is in liquid form; the derived polymer can be shaped into asymmetrical implants by injection molding. The characteristic of injectability makes it appropriate for the orthopedic implant procedures.

Photo cross-linkable, polyanhydrides have also been developed for the orthopedic application predominantly focusing on achieving good mechanical strength. The polymer is synthesized starting from dimethacrylated anhydrides. The curing of the macro monomer is achieved by ultraviolet and visible light. The monomer choice affects the material mechanical properties and degradation.

Injectable photo-crosslinked polyanhydrides can be used to renew irregularly shaped bone imperfection or soft tissue repairs. The degradation occurred by means of hydrolysis of anhydride bonds, subsequently the hydrolysis of imide bonds of these copolymers. Hydrolytic degradation of polyanhydride is nontoxic and results in a solution composed of the diacid molecules and water-soluble linear methacrylic acid molecules. Thus, the main advantages of such scaffolds are non-toxicity, injectability, low degradation tendency, and high bio-compatibility. The physical properties can be modified during the scaffold’s fabrication.

This table summarizes the mechanical characteristics, applications and processing methods for biodegradable polymers vs. hydroxyapatites and blends.

Table 1 -

Material Compressive
Strength,
MPa
Modulus,
GPa
Crystallinity Elongation, %
HAP and blends 20-43   40%  
Polyglycolide   7.0 45-55% 15-20
Polylactide 20-40 2.7 37%  
Polylactide-co-glycolide
85/15
20-40 2.0 amorphous 3-10
Polylactide-coglycolide 50/50 20-40 2 amorphous 3-10
Polycaprolactone   0.4   300-500
PPF 2-30 2-3 37  
Polyanhydride 25-27     14-85

Material Degradation time, weeks Degradation product
Application Processing method
HAP and blends bulk   Implants, adhesion barriers SC, SF, IM
Polyglycolide 6-12 Glycolic acid Suture anchors, menixcus, drug delivery SC, SFF, CM
Polylactide 12-18 Lactic acid Fracture fixation, suture anchors, meniscus SC,SFF
Polylactide-co-glycolide
85/15
5-6 Lactic acid Suture anchors, screws SC, SFF, CM
Polylactide-coglycolide 50/50 1-2 Lactic and glycolic acid Plates, mesh, screws SC, SFF, CM
Polycaprolactone > 24 Caproic acid Suture coating, implants SC, SFF, CM
PPF >24 Fumaric acid, propylene glycol Orthopedic implants, foam coatings,
drug delivery
Inject able PP further cross-linked via free radicals initiation
Polyanhydride 1.4-14   Bone replacement, medical devices  

Explanations of processing methods: SC - solution casting, CM - compression molding, SFF - solid free forming, IM - injection molding, EFD - emulsion freeze drying

Natural polymer materials

mother and daughter

Natural polymer materials

Another area of research is materials from nature as the bases for synthetic bone. Natural polymers can serve as templates - a scaffolding - for cell attachment and growth. (Unfortunately some of these materials can stimulate an immune response and cause the implant to be rejected.) Due to their excellent biocompatibility collagen, fibrin, agarose (polysaccharides derived from agar), chitosan, and alginate materials are used in the bone and cartilage tissue engineering. The microstructures of these materials are highly patterned and suitable for cell growth.

However there are some disadvantages to these materials. such as (1) high cost, (2) unreliability in obtaining the materials in bulk quantity, and (3) difficulties the processing the materials for suitable use in a body.

The degradation rate of natural polymer materials may vary from patient to patient.

New Plastics

In 2013 British researchers announced they had developed scaffolding of a combination of plastics that could be used to replace bones. The blood vessels would grow inside the scaffolding and bone cells would form there. The plastic would degrade over time according to press reports. Technical details were not included in the popular press.

Diamond?

Scientists have experimented with diamond implants as a method to improve bone strength. Spherical diameters measuring 5 nanometers or so in diameter can carry proteins into bone and tooth tissue. This form of treatment is early in development but experts hope the technology could lead to new methods to address osteonecrosis and even osteoporosis.

Cement

Doctors use cements to anchor artificial implants and to build up the spine in vertebroplasty and kyphoplasty procedures. Polymethyl methacrylate is the most common cement; magnesium phosphate cement, calcium sulfate cement, acrylic bone cements, and calcium phosphate cements are employed.

The effect of cement creep and cement fatigue damage on the micromechanics of the cement-bone interface.

Properties of composite specimens of old and new bone cement.

Multi-axial loading micromechanics of the cement-bone interface in postmortem retrievals and lab-prepared specimens.

Article: How coral revolutionized human bone repair.

Biomimetic Polymer Composite Materials for Bone Repair - National Research Council of Canada

Emerging Treatments

The Physiology of Bone

 

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