Prefabrication of a large pedicled bone graft by engineering the germ for de novo vascularization and osteoinduction

Epple, Christian; Haumer, Alexander; Ismail, Tarek; Lunger, Alexander; Scherberich, Arnaud; Schaefer, Dirk J.; Martin, Ivan

doi:10.1016/j.biomaterials.2018.11.008

Cited by 35 publications

(28 citation statements)

References 36 publications

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“…This was also detected in our study by the large fibrotic compartments encountered within macropellet explants (Figure ). In addition, when chondrogenic and hypertrophic pellets were fused into larger structures, limited remodeling in vivo was shown. Hence, we designed cell microspheroids (comprised of 250 cells) that would not exceed 150 µm in diameter to match with the length scale that diffusible signals can be transported and to mimic the initial developmental event of growth plate formation (condensation) whereby only a few hundred cells are needed .…”

Section: Discussionmentioning

confidence: 99%

Developmentally Engineered Callus Organoid Bioassemblies Exhibit Predictive In Vivo Long Bone Healing

et al. 2019

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Clinical translation of cell‐based products is hampered by their limited predictive in vivo performance. To overcome this hurdle, engineering strategies advocate to fabricate tissue products through processes that mimic development and regeneration, a strategy applicable for the healing of large bone defects, an unmet medical need. Natural fracture healing occurs through the formation of a cartilage intermediate, termed “soft callus,” which is transformed into bone following a process that recapitulates developmental events. The main contributors to the soft callus are cells derived from the periosteum, containing potent skeletal stem cells. Herein, cells derived from human periosteum are used for the scalable production of microspheroids that are differentiated into callus organoids. The organoids attain autonomy and exhibit the capacity to form ectopic bone microorgans in vivo. This potency is linked to specific gene signatures mimicking those found in developing and healing long bones. Furthermore, callus organoids spontaneously bioassemble in vitro into large engineered tissues able to heal murine critical‐sized long bone defects. The regenerated bone exhibits similar morphological properties to those of native tibia. These callus organoids can be viewed as a living “bio‐ink” allowing bottom‐up manufacturing of multimodular tissues with complex geometric features and inbuilt quality attributes.

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Section: Discussionmentioning

confidence: 99%

Developmentally Engineered Callus Organoid Bioassemblies Exhibit Predictive In Vivo Long Bone Healing

et al. 2019

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“…For instance, we previously found that hiPSC-derived MSC engineered bone constructs (~0.5 cm in size) remained viable for 12 weeks in a subcutaneous site, continued to develop, and functional blood vessels were found within the interior portions of the transplants (De Peppo et al, 2013). Furthermore, the application of tissue engineering protocols involving the endochondral differentiation pathway, which is predominant in the healing of long bones, might allow enhanced survival, vascularization, and remodeling of the transplanted hypertrophic cartilage grafts toward new bone regeneration (Bernhard et al, 2017; Epple et al, 2019).…”

Section: Mscs-based Therapies and Bone Tissue Engineeringmentioning

confidence: 99%

Mesenchymal Stromal Cell-Based Bone Regeneration Therapies: From Cell Transplantation and Tissue Engineering to Therapeutic Secretomes and Extracellular Vesicles

Presen

Traweger

Gimona

et al. 2019

Front. Bioeng. Biotechnol.

105

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Effective regeneration of bone defects often presents significant challenges, particularly in patients with decreased tissue regeneration capacity due to extensive trauma, disease, and/or advanced age. A number of studies have focused on enhancing bone regeneration by applying mesenchymal stromal cells (MSCs) or MSC-based bone tissue engineering strategies. However, translation of these approaches from basic research findings to clinical use has been hampered by the limited understanding of MSC therapeutic actions and complexities, as well as costs related to the manufacturing, regulatory approval, and clinical use of living cells and engineered tissues. More recently, a shift from the view of MSCs directly contributing to tissue regeneration toward appreciating MSCs as “cell factories” that secrete a variety of bioactive molecules and extracellular vesicles with trophic and immunomodulatory activities has steered research into new MSC-based, “cell-free” therapeutic modalities. The current review recapitulates recent developments, challenges, and future perspectives of these various MSC-based bone tissue engineering and regeneration strategies.

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“…Axial vascularization of TE constructs may be provided by the principles of prelamination 238 and prefabrication. 239 Prelamination involves the implantation of a nonvascularized TE construct into a highly vascularized territory (eg, a flap) which then serves to create an axially vascularized unit suitable for free transplantation via its pedicle. Warnke et al 240 showed that axially vascularized flaps may serve as an "in vivo bioreactor" for ex vivo engineered bone constructs.…”

Section: Blood Vesselsmentioning

confidence: 99%

Tissue Engineering and Regenerative Medicine in Craniofacial Reconstruction and Facial Aesthetics

Borrelli

Longaker

et al. 2020

Journal of Craniofacial Surgery

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The craniofacial region is anatomically complex and is of critical functional and cosmetic importance, making reconstruction challenging. The limitations of current surgical options highlight the importance of developing new strategies to restore the form, function, and esthetics of missing or damaged soft tissue and skeletal tissue in the face and cranium. Regenerative medicine (RM) is an expanding field which combines the principles of tissue engineering (TE) and self-healing in the regeneration of cells, tissues, and organs, to restore their impaired function. RM offers many advantages over current treatments as tissue can be engineered for specific defects, using an unlimited supply of bioengineered resources, and does not require immunosuppression. In the craniofacial region, TE and RM are being increasingly used in preclinical and clinical studies to reconstruct bone, cartilage, soft tissue, nerves, and blood vessels. This review outlines the current progress that has been made toward the engineering of these tissues for craniofacial reconstruction and facial esthetics.

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Prefabrication of a large pedicled bone graft by engineering the germ for de novo vascularization and osteoinduction

Cited by 35 publications

References 36 publications

Developmentally Engineered Callus Organoid Bioassemblies Exhibit Predictive In Vivo Long Bone Healing

Developmentally Engineered Callus Organoid Bioassemblies Exhibit Predictive In Vivo Long Bone Healing

Mesenchymal Stromal Cell-Based Bone Regeneration Therapies: From Cell Transplantation and Tissue Engineering to Therapeutic Secretomes and Extracellular Vesicles

Tissue Engineering and Regenerative Medicine in Craniofacial Reconstruction and Facial Aesthetics

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