Scaffold Translation: Barriers Between Concept and Clinic

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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90495/1/ten-2Eteb-2E2011-2E0251.pd

Unilateral atrophy of the cheek: autologous fat injection as treatment of choice.

Item does not contain fulltextLipodystrophies are a set of heterogeneous conditions resulting from defective lipid metabolism and characterized by adipose tissue atrophy. We report on a 54-year-old woman who presented at the Department of Oral and Maxillofacial Surgery with an increasing unilateral atrophy of her left cheek for the past 3 years. The patient's history showed that she had sustained a left zygoma fracture 35 years ago but did not have any other disease. According to the patient's wish, a correction of the left cheek was performed by autologous fat injection, which led to a highly acceptable postoperative result. We compare this treatment with different alternatives

Endocultivation: 3D printed customized porous scaffolds for heterotopic bone induction.

Contains fulltext : 80767.pdf (publisher's version ) (Closed access)The aim of this study was to evaluate the ability of computer assisted designed (CAD) synthetic hydroxyapatite and tricalciumphosphate blocks to serve as precise scaffolds for intramuscular bone induction in a rat model. A central channel to allow for vessel pedicle or nerve integration was added. Natural bovine hydroxyapatite blocks served as controls to evaluate and compare biocompatibility of the new matrices. Individually designed 3D-printed rounded and porous hydroxyapatite (HA) and tricalcium phosphate (TCP) blocks were placed in pouches in the Musculus latissimus dorsi in 12 Lewis rats bilaterally. Bovine hydroxyapatite blocks with and without a central channel served as controls. Simultaneously, 200 microg rhBMP-2 in 1 ml sodium chloride was injected on both sides. For 8 weeks, bone generation was monitored by computer tomography and fluorescence labeling. The increase rates of bone density in CT examinations were higher in the HA groups (184-220 HU 8 weeks after implantation) compared to the TCP group (18 HU; p<0.0001). Microradiography and fluorescence microscopy 8 weeks after implantation showed new bone formation for all materials tested. For all scaffolds, toluidine staining revealed vital bone directly on the scaffold materials but also in the gaps between. It can be concluded from our data that the specially shaped hydroxyapatite and tricalcium phosphate blocks tested against the bovine hydroxyapatite blocks showed good biocompatibility and osteoinductivity in vivo. Further studies should explore if the stability of the individually designed blocks is sufficient to cultivate larger replacements without an external matrix for support

Endocultivation: does delayed application of BMP improve intramuscular heterotopic bone formation?

Contains fulltext : 88676.pdf (publisher's version ) (Closed access)INTRODUCTION: The time point of Bone morphogenetic protein (BMP) delivery on matrices in vivo may play an important role. Delayed application could be advantageous as this would allow soft tissue (ST) ingrowth and vascularisation of scaffolds prior to BMP-loading. The aim of this study was to compare the application of BMP injected simultaneously during matrix implantation with delayed application four weeks after matrix implantation for endocultivation in a rat model. MATERIAL AND METHODS: Bovine hydroxyapatite blocks were placed in pouches in the Musculus latissimus dorsi in 6 Lewis rats unilaterally to allow for soft tissue ingrowth. Four weeks later, a second block was inserted on the contralateral side of each rat. At that time point, 100microg rhBMP-2 in 2ml sodium chloride was injected on both sides to induce bone formation. For eight weeks, bone regeneration was monitored by computed tomography (CT) and fluorescent labelling. RESULTS: The simultaneous and delayed BMP application groups were significantly different (p=0.01). Slightly lower bone densities were seen for the delayed BMP application with a mean of 588 Hounsfield Units (HU) (standard deviation (SD) 30HU). Simultaneous BMP application revealed slightly higher densities with a mean of 633HU (SD 30HU). The largest differences were observed when comparing bone density directly after implantation or at the end of the observation period (p<0.0001). CONCLUSION: Bone density was slightly lower in the case of delayed application of BMP-2. The increase of bone density after application of BMP-2 was similar for both groups. Thus, delayed application of BMP had no advantageous effect in this particular study design. Further studies are needed to explore if varying delays, different material designs or special BMP application devices may alter these results.1 januari 201