The Few Who Made It: Commercially and Clinically Successful Innovative Bone Grafts

Abstract

Bone reconstruction techniques are mainly based on the use of tissue grafts and artificial scaffolds. The former presents well-known limitations, such as restricted graft availability and donor site morbidity, while the latter commonly results in poor graft integration and fixation in the bone, which leads to the unbalanced distribution of loads, impaired bone formation, increased pain perception, and risk of fracture, ultimately leading to recurrent surgeries. In the past decade, research efforts have been focused on the development of innovative bone substitutes that not only provide immediate mechanical support, but also ensure appropriate graft anchoring by, for example, promoting de novo bone tissue formation. From the countless studies that aimed in this direction, only few have made the big jump from the benchtop to the bedside, whilst most have perished along the challenging path of clinical translation. Herein, we describe some clinically successful cases of bone device development, including biological glues, stem cell-seeded scaffolds, and gene-functionalized bone substitutes. We also discuss the ventures that these technologies went through, the hindrances they faced and the common grounds among them, which might have been key for their success. The ultimate objective of this perspective article is to highlight the important aspects of the clinical translation of an innovative idea in the field of bone grafting, with the aim of commercially and clinically informing new research approaches in the sector.

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

“…Recent studies have revealed varying results which cast doubt on whether the additional use of PRP with other grafting materials in the treatment of infrabony defects and sinus augmentation provides any added benefits [ 89 , 177 , 179 , 180 , 181 ]. Since the early 2000s, BMP-2 and BMP-7 have been the most commonly used USFDA approved growth factors for bone grafting procedures in dentistry and function as the active components of two major commercial products— Infuse TM and Osigraft TM , respectively [ 182 ]. However, the production of Osigraft TM has since been halted and the use of Infuse TM has been associated with a large number of life-threatening complications [ 182 ].…”

“…Since the early 2000s, BMP-2 and BMP-7 have been the most commonly used USFDA approved growth factors for bone grafting procedures in dentistry and function as the active components of two major commercial products— Infuse TM and Osigraft TM , respectively [ 182 ]. However, the production of Osigraft TM has since been halted and the use of Infuse TM has been associated with a large number of life-threatening complications [ 182 ]. Although the use of GFBSs has presented a promising area for the introduction of new bone substitutes, novel bioactivated products with GFs have generally not progressed beyond the animal study stage in recent years.…”

“…The products which have progressed beyond this stage, such as Augment TM have used recombinant growth factors derived from human platelets (rhPDGF-BB) and rhBMPs [ 178 ]. These products are generally used in combination with a structural scaffold or carriers such as allograft material, collagen sponges, titanium mesh or β-TCP/HA [ 178 , 182 ]. The use of bioactivated products with growth factors have been indicated for use in bilateral maxillary sinus augmentation, ridge augmentation, coating on implants and bony and ridge defects [ 178 ].…”

“…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 ]. 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 ].…”

Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration

“…It is noteworthy that SmartBone ® is also available as a new CE-labeled class III medical device, and it has a vast clinical record being also commercially available as a bone substitute for bone regenerative surgeries in all skeletal districts for oral, maxillofacial, orthopedic, and oncologic indications [ 11 , 12 , 13 , 14 ]. This allows the current developments to have a robust path into translating research from bench to bed and to market finally [ 15 ].…”