Advances in Growth Factor Delivery for Bone Tissue Engineering

Abstract

Shortcomings related to the treatment of bone diseases and consequent tissue regeneration such as transplants have been addressed to some extent by tissue engineering and regenerative medicine. Tissue engineering has promoted structures that can simulate the extracellular matrix and are capable of guiding natural bone repair using signaling molecules to promote osteoinduction and angiogenesis essential in the formation of new bone tissues. Although recent studies on developing novel growth factor delivery systems for bone repair have attracted great attention, taking into account the complexity of the extracellular matrix, scaffolding and growth factors should not be explored independently. Consequently, systems that combine both concepts have great potential to promote the effectiveness of bone regeneration methods. In this review, recent developments in bone regeneration that simultaneously consider scaffolding and growth factors are covered in detail. The main emphasis in this overview is on delivery strategies that employ polymer-based scaffolds for spatiotemporal-controlled delivery of both single and multiple growth factors in bone-regeneration approaches. From clinical applications to creating alternative structural materials, bone tissue engineering has been advancing constantly, and it is relevant to regularly update related topics.

Bone Grafts and Substitutes in Dentistry: A Review of Current Trends and Developments

“…Growth factors (GFs) such as BMPs, platelet-derived growth factors (PDGFs) and insulin-like growth factors (IGFs) have been found to possess osteoinductive properties, allowing for accelerated bone regeneration in bony defects [ 176 ]. In the dental field, the first use of bioactivated materials with growth factors is in the use of plasma rich in growth factors (PRGF), platelet rich plasma (PRP) and plasma rich in fibrin (PRF) to accelerate bone healing in patients with bisphosphonate related osteonecrosis of the jaw (BRONJ) [ 177 , 178 ].…”

“…Currently, several concerns remain regarding the effective use of GFBSs in targeted bone regeneration. These include the need for the inclusion of a structural scaffold due to the lack of osteoconductive capability of GFBSs and the need for GFs to reach the target tissue whilst retaining their bioactivity during the therapeutic time frame [ 176 ]. The development of a delivery method that is able to satisfy both these needs simultaneously has been regarded as extremely challenging to the point of being near-impossible [ 182 ].…”

“…The development of a delivery method that is able to satisfy both these needs simultaneously has been regarded as extremely challenging to the point of being near-impossible [ 182 ]. Strategies which address these concerns that have been proposed include entrapment of GFs within the scaffold, covalent or non-covalent binding of GFs to the scaffold and the use of micro/nanoparticles as GF reservoirs allowing for prolonged controlled release over time [ 176 ].…”

“…There has been a recent trend for the incorporation of osteoinductive growth factors and/or MSCs with a structural scaffold to increase the material’s bone regenerative potential and inhibit undesirable inflammatory recipient responses. Additionally, there has also been increasing interest in the controlled time-release delivery of growth factors as a means of maintaining their bioactivity over the therapeutic window [ 176 ]. Thus, the development of novel grafting materials should focus on incorporating as many ideal biological parameters as possible, whilst ensuring that such materials would be readily available, cost-effective and clinically evidence based.…”

Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration

“…Although these soluble factors have approved applications in bone regeneration, they present several limitations that could restrict their clinical usage [ 92 , 93 ]. For instance, early GF delivery approaches [ 94 ] resulted in low availability of bioactive GFs due to their rapid degradation in vivo, short half-life in physiological conditions, and deactivation by enzymes [ 95 ]. In fact, the poor pharmacokinetics of these proteins has led to the delivery of high doses, with the consequent increase in the risk of serious side effects.…”