Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering

Abstract

Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue. However, micro-CT fails to provide spatiotemporal information on biological processes ongoing during bone regeneration. Conversely, due to the versatile applicability and cost-effectiveness, single photon emission computed tomography (SPECT) would be an ideal technique for assessing such biological processes with high sensitivity and for nuclear imaging comparably high resolution (<1 mm). Herein, we employ modular designed poly(ethylene glycol)-based hydrogels that release bone morphogenetic protein to guide the healing of critical sized calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and micro-CT evaluations we determine the spatiotemporal course of bone formation and remodeling within this synthetic hydrogel implant. End point evaluations by high resolution micro-CT and histological evaluation confirm the value of this approach to follow and optimize bone-inducing biomaterials.

A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration

“…PET/CT scanning has good spatial resolution properties and has been used in previous studies to assess the healing of defects. In vivo metabolic imaging has several benefits: very early bone forming activity can be visualized, the methods is applicable to biomaterials with a radiodensity similar to that of native bone (e.g., hydroxyapatite), and bone remodeling sites can be monitored directly . Active bone formation sites can be visualized and quantified by bone‐specific uptake of [ 18 F]‐NaF.…”

Photobiomodulation Therapy (PBMT) Applied in Bone Reconstructive Surgery Using Bovine Bone Grafts: A Systematic Review

“…In extensive tissue defects, repair can become a challenge, requiring the use of bone grafts, implants or biomaterials. At this time, tissue engineering comes into play in helping the development of components that can lead to or assist in the reconstruction of lost tissue [29][30][31].…”

Enzyme responsive GAG-based natural-synthetic hybrid hydrogel for tunable growth factor delivery and stem cell differentiation

“…With operator controlled siteand time-specific modification of materials properties such as presentation of adhesion sites, material stiffness or release of growth factors, first tools are now emerging, which provide the exciting possibility to control biological processes in four dimensions [31].In order to integrate the increasing number of available molecular tools in a modular fashion, some of us have developed a PEG-hydrogel platform, which allows for the flexible composition of engineered building blocks [32].This transglutaminase cross-linked PEG (TG-PEG) hydrogel platform is based on 8-arm PEG-vinyl sulfone (8-PEG-VS) which by a Michael-type addition reaction are functionalized with two complementary short glutamine (TG-Gln; NQEQVSPL-ERCG-NH2) or lysine peptides (TG-Lys; Ac-FKGG-ERCG-NH2) that serve as specific substrates for thrombin activated transglutaminase factor XIII (FXIIIa). When using matrix metalloproteinase sensitive lysine peptides (TG-MMP-Lys; Ac-FKGG-GPQGIWGQ-ERCG-NH2) and the enzymatic incorporation of a Gln-tagged RGD (TG-RGD-Gln; NQEQVSPL-RGDSPG-NH2) these FXIIIa cross-linked hydrogels have been shown to support growth, migration and differentiation of osteoblasts or MSCs in vitro as well as the bone morphogenetic protein induced healing of bone defects [33,34]. These hydrogels, utilizing FXIIIa-mediated gelation, are highly biocompatible, can be formed under physiological buffer conditions and neither require chemical initiators, UV irradiation, or temperature changes at the site of formation [35].…”

“…This transglutaminase cross-linked PEG (TG-PEG) hydrogel platform is based on 8-arm PEG-vinyl sulfone (8-PEG-VS) which by a Michael-type addition reaction are functionalized with two complementary short glutamine (TG-Gln; NQEQVSPL-ERCG-NH2) or lysine peptides (TG-Lys; Ac-FKGG-ERCG-NH2) that serve as specific substrates for thrombin activated transglutaminase factor XIII (FXIIIa). When using matrix metalloproteinase sensitive lysine peptides (TG-MMP-Lys; Ac-FKGG-GPQGIWGQ-ERCG-NH2) and the enzymatic incorporation of a Gln-tagged RGD (TG-RGD-Gln; NQEQVSPL-RGDSPG-NH2) these FXIIIa cross-linked hydrogels have been shown to support growth, migration and differentiation of osteoblasts or MSCs in vitro as well as the bone morphogenetic protein induced healing of bone defects [33,34]. These hydrogels, utilizing FXIIIa-mediated gelation, are highly biocompatible, can be formed under physiological buffer conditions and neither require chemical initiators, UV irradiation, or temperature changes at the site of formation [35].…”