Biomimetic tubular nanofiber mesh and platelet rich plasma-mediated delivery of BMP-7 for large bone defect regeneration

Berner, Arne; Boerckel, Joel D.; Saifzadeh, Siamak; Steck, Roland; Ren, Jiongyu; Vaquette, Cédryck; Zhang, Qi Yi; Nerlich, Michael; Guldberg, Robert E.; Hutmacher, Dietmar W.; Woodruff, Maria A.

doi:10.1007/s00441-011-1298-z

Cited by 74 publications

(49 citation statements)

References 30 publications

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“…We subsequently took the next step towards clinical translation by performing small animal studies using rat, mice and rabbit models (207)(208)(209). As reviewed in detail in Reference (200), we were able to demonstrate the in vivo capability of our composite scaffolds in combination with growth factors or cells to promote bone regeneration within ectopic sites or critical sized cranial defects in the small animal models.…”

Section: Taking Composite Scaffold Based Bone Tissue Engineering Frommentioning

confidence: 95%

Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

et al. 2013

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The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental "origin" require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.

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Section: Taking Composite Scaffold Based Bone Tissue Engineering Frommentioning

confidence: 95%

Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

et al. 2013

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“…In line with this, superior bone formation was shown in bicortical mandible defects in rabbits treated with a composite of porous bone mineral and bio-guide membrane supplemented with PRP containing 699 × 10 3 platelets/µL (4.4-fold enrichment) [46]. It was also suggested that PRP can be utilized for the delivery of BMP-7 within a calcium phosphate-coated nanofiber mesh tube, where BMP-7 delivery enhanced bone formation and biomechanical properties in rat segmental femur defects [47].…”

Section: Prp In Tissue-engineered Constructsmentioning

confidence: 99%

Platelet-Rich Plasma in Tissue Engineering: Hype and Hope

Lang

Loibl²,

Herrmann³

2018

Eur Surg Res

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Background: Platelet-rich plasma (PRP) refers to an enriched platelet suspension in plasma. In addition to the clinical application of PRP in the context of various orthopedic diseases and beyond, PRP and platelet lysate (PL) have been in focus in the field of tissue engineering. In this review, we discuss the application of PRP as a cell culture supplement and as part of tissue engineering strategies, particularly emphasizing current hurdles and ambiguities regarding the efficacy of PRP in these approaches. Summary: As a putative autologous replacement for animal-derived supplements such as fetal calf serum (FCS), PRP has been applied as cell culture supplement for the expansion of stem and progenitor cells for tissue engineering applications and cell therapies. Attributed to the high content of growth factors in platelets, PRP has been shown to promote cell growth, which was mostly superior to standard cultures supplemented with FCS, while the differentiation capacity of progenitor cells seems not to be affected. However, it was also suggested that cultivation of cells with PRP significantly alters the protein expression profile in cells in comparison to FCS, indicating that the influence of PRP on cell behavior should be thoroughly investigated. Moreover, different PRP preparation methods and donor variations have to be considered for the use of PRP under good manufacturing practice conditions. PRP has been used for various tissue engineering applications in the context of bone, cartilage, skin, and soft tissue repair, where most studies were conducted in the field of bone tissue engineering. These approaches take either advantage of the release of chemoattractive, angiogenic, proliferative, and putatively pro-regenerative growth factors from PRP, and/or the hydrogel properties of activated PRP, making it suitable as a cell delivery vehicle. In many of these studies, PRP is combined with biomaterials, cells, and in some cases recombinant growth factors. Although the experimental design often does not allow conclusions on the pro-regenerative effect of PRP itself, most publications report beneficial effects if PRP is added to the tissue-engineered construct. Furthermore, it was demonstrated that the release of growth factors from PRP may be tailored and controlled when PRP is combined with materials able to capture growth factors. Key Messages: Platelet-derived preparations such as PRP and PL represent a promising source of autologous growth factors, which may be applied as cell culture supplement or to promote regeneration in tissue-engineered constructs. Furthermore, activated PRP is a promising candidate as an autologous cell carrier. However, the studies investigating PRP in these contexts often show conflicting results, which most likely can be attributed to the lack of standardized preparation methods, particularly with regard to the platelet content and donor variation of PRP. Ultimately, the use of PRP has to be tailored for the individual application.

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“…The scaffolds were produced by fused deposition modeling, as previously reported [17,25]. To enhance the osteoinductive properties of the scaffold, the surface was coated with a layer of calcium phosphate (CaP) using a previously published protocol [28]. The scaffolds had a porosity of 74% and a 0/90°lay down pattern.…”

Section: Scaffold Design and Preparationmentioning

confidence: 99%

Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model

Berner

Henkel

Woodruff

et al. 2015

Stem Cells Translational Medicine

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Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:503-512 SIGNIFICANCEFrom a translational point of view, a comprehensive study is presented, the results of which show that percutaneous injection of allogenic BMSCs into the biodegradable composite scaffold 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed results comparable to those of the clinical gold standard, namely autologous autograft. To the authors' knowledge, this is the first study to display in a validated preclinical large animal model that delayed allogenic cell transplantation could provide clinical treatment alternatives for challenging bone defects in the future.

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Biomimetic tubular nanofiber mesh and platelet rich plasma-mediated delivery of BMP-7 for large bone defect regeneration

Cited by 74 publications

References 30 publications

Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

Platelet-Rich Plasma in Tissue Engineering: Hype and Hope

Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model

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