Scaffold Translation: Barriers Between Concept and Clinic

Abstract

Translation of scaffold-based bone tissue engineering (BTE) therapies to clinical use remains, bluntly, a failure. This dearth of translated tissue engineering therapies (including scaffolds) remains despite 25 years of research, research funding totaling hundreds of millions of dollars, over 12,000 papers on BTE and over 2000 papers on BTE scaffolds alone in the past 10 years (PubMed search). Enabling scaffold translation requires first an understanding of the challenges, and second, addressing the complete range of these challenges. There are the obvious technical challenges of designing, manufacturing, and functionalizing scaffolds to fill the Form, Fixation, Function, and Formation needs of bone defect repair. However, these technical solutions should be targeted to specific clinical indications (e.g., mandibular defects, spine fusion, long bone defects, etc.). Further, technical solutions should also address business challenges, including the need to obtain regulatory approval, meet specific market needs, and obtain private investment to develop products, again for specific clinical indications. Finally, these business and technical challenges present a much different model than the typical research paradigm, presenting the field with philosophical challenges in terms of publishing and funding priorities that should be addressed as well. In this article, we review in detail the technical, business, and philosophical barriers of translating scaffolds from Concept to Clinic. We argue that envisioning and engineering scaffolds as modular systems with a sliding scale of complexity offers the best path to addressing these translational challenges.

Integration of mechanotransduction concepts in bone tissue engineering

“…This strategy, while demonstrating its pertinence in multiple in vivo studies, hardly leads to clinical applications as recently reviewed specifically for scaffold used in bone tissue engineering applications (Hollister and Murphy 2011). In parallel, the importance of mechanical stimulation on the behaviour of biomaterials has been identified since several years.…”

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

“…Various methods of scaffold fabrication yield different pore size distributions from a few nanometers to hundreds of micrometers and have been examined for bone regeneration. On the materials side, tricalcium phosphate (TCP)-based scaffolds loaded with biologics have been examined, but have not yet provided a highly controlled release pattern of growth factors and loading amenable to clinical implementation (8). Hybrid materials, including various polymer/calcium phosphate composites, have been explored with tunable degradation properties.…”

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

“…[73][74][75][76][77][78][79] The use of supraphysiological levels of BMP-2 might activate a negative feedback loop through BMP inhibitors such as noggin or sclerotin, which are upregulated by the presence of BMP. 80,81 Moreover, inflammation, edema, and heterotopic bone formation can occur when such high concentrations are used. 82 Complications associated to the use of recombinant human BMP-2 have been reported, including death, dysphagia, heterotopic bone formation in the spinal canal, or airway compression in cervical spine fusion.…”

“…Food and Drug Administration (FDA) has been especially cautious since those reports and at this point, 75% of the spine fusions are still performed by using traditional bone grafting methods. 81 Therefore, despite its tremendous potential, BMP-2 use still presents some disadvantages regarding its bone regeneration potential. The high-cost treatment and the simultaneous stimulation of development of both osteoblasts and osteoclasts with opposite effects are additional drawbacks.…”