Problem: The current clinical “gold standard” for repair of critical size bone fractures is the autologous bone graft, which has shown some success but leaves the patient with secondary complications at the site of the donor tissue harvest. Other treatments include allografts (tissue taken from cadavers) and plastic or metal implants. Allografts are often biologically rejected and carry a serious risk of immune rejection or disease transmission. Synthetic implants are usually permanent, do not promote tissue regeneration and are mechanically incompatible with native tissue. This compliance mismatch leads to mechanical failure or erosion of the neighboring bone. New endeavors with tissue engineering use biodegradable scaffolding materials to direct tissue regeneration. However, this has shown limited success due to the multiple facets of tissue regeneration. Generally, polymers may differ in strength, compression and torsion, and they may not promote cell growth and tissue infiltration. Soft materials that are biocompatible may lack the mechanical properties necessary for orthopedic applications. To resolve these principle issues, we devised a strategy using bionanoscaffolds (BNS) that combines the mechanical advantages of biodegradable synthetic polymers with the biological functions of natural biomaterial scaffolds. This approach achieves the correct strength requirements while enhancing the regeneration of healthy bone tissue at the fracture site.
Approach: Bionanoscaffolds for post-traumatic osteoregeneration are a new class of composites, biologically active fracture putty materials, consisting of several fundamental building blocks. The principle components of the BNS include the following:
- Biodegradable, biocompatible polymeric scaffolds fabricated as nonporous elements for the mechanical stabilization of segmental defects
- A bioactive biomimetic osteogenic sponge that integrates factor-releasing particles to promote immediate angiogenesis and rapid regeneration of bone tissue within the defect; this scaffold can be enriched with multi-substituted hydroxyapatite crystals, which enhance bone deposition and accelerate healing
- Nanoporous silicon enclosures formulated to control the release of bioactive molecules and factors able to accelerate healing and promote tissue reconstruction while fighting infection and biofilm formation
- Self-assembling amphiphilic peptides that stimulate the regeneration of bone and soft tissue, including neural and vascular functions
- Mesenchymal stem cells are adult stem cells harvested from cortical bone, marrow or adipose tissue that are capable of differentiating into mature skeletal cells and regenerating orthopedic tissue matrix
The BioNanoScaffold approach for bone tissue engineering. (A) A scaffold based on synthetic and natural polymers is implanted or injected into the fracture site. (B) The scaffold is made of highly porous, biomimetic collagen organized in randomly distributed fibers, enriched with hydroxyapatite crystals and alginate microspheres, and embedded with stem cells and delivery platforms for growth factors, differentiating stimuli, and antibiotics. (C) Upon implantation, the alginate spheres start degrading, progressively releasing their contents within the scaffold. The synergy between stem cells and growth and differentiating factors induces the reorganization of the scaffold. Osteoblasts remodel the collagen fibers and lay down additional extracellular matrix, and osteoid and hydroxyapatite crystals. (D) After a month, the fracture is healed and the implanted materials have been resorbed.
The BNS can be formulated into an injectable paste for irregular defects or space-maintaining filler in cranio-facial, spine and other fracture repairs. This material is based on calcium alginate microbeads that embed and protect all of the components as previously mentioned during delivery to the patient. Upon injection, the alginate beads progressively degrade over time, releasing a framework of biological factors, cellular components, and bioactive compounds that promote osteogenesis and early vascularization. The alginate beads can be tailored by size, porosity and overall stability, so that their degradation time and mechanical properties can be adjusted to those required by the specific application.