From natural bone grafts to tissue engineering therapeutics: Brainstorming on pharmaceutical formulative requirements and challenges

Baroli, Bianca Maria

doi:10.1002/jps.21528

Cited by 164 publications

(130 citation statements)

References 489 publications

(573 reference statements)

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“…However, while several of the proposed methods have been conveniently adapted for incorporating growth factors (e.g. Baroli 2009), only a limited number of techniques have been specifically used for fabricating scaffolds with therapeutic drug-delivery capability (table 2). In the following sections we summarize the progress in the field of bone TE scaffold development with potential application as therapeutic drug-delivery vehicles.…”

Section: Scaffold Materialsmentioning

confidence: 99%

“…Different strategies followed to deliver specific growth factors (e.g. cytokines and hormones); morphogens and proteins using TE scaffolds to stimulate cellular adhesion, proliferation and differentiation, thus promoting bone regeneration, have been proposed and these have been reviewed in the literature (Saltzman & Olbricht 2002;Chung & Park 2007;Habraken et al 2007; Lee & Shin 2007;Baroli 2009). However, there has been no previous review, to the authors' knowledge, focusing exclusively on TE approaches to deliver therapeutic (synthetic) drugs.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, it could be beneficial to mimic the blood/plasma flow speed observed at the site of the scaffold's implantation (Baroli 2009). Further, and surprisingly, there is very limited reported information regarding the stability of the drugs involved in the studies, in particular the thermal stability.…”

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confidence: 99%

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Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds

Mouriño

Boccaccını

2009

J. R. Soc. Interface.

462

294

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This paper provides an extensive overview of published studies on the development and applications of three-dimensional bone tissue engineering (TE) scaffolds with potential capability for the controlled delivery of therapeutic drugs. Typical drugs considered include gentamicin and other antibiotics generally used to combat osteomyelitis, as well as anti-inflammatory drugs and bisphosphonates, but delivery of growth factors is not covered in this review. In each case reviewed, special attention has been given to the technology used for controlling the release of the loaded drugs. The possibility of designing multifunctional three-dimensional bone TE scaffolds for the emerging field of bone TE therapeutics is discussed. A detailed summary of drugs included in three-dimensional scaffolds and the several approaches developed to combine bioceramics with various polymeric biomaterials in composites for drug-delivery systems is included. The main results presented in the literature are discussed and the remaining challenges in the field are summarized with suggestions for future research directions.

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Section: Scaffold Materialsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds

Mouriño

Boccaccını

2009

J. R. Soc. Interface.

462

294

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“…Most of these complications can be prevented by filling the bone defect with materials that can replace the bone immediately after surgery and enhance the healing speed by stimulating new bone creation. Studies focused on replacement of the damaged tissues using autologous and allogeneic transplantation revealed considerable limitations and complication (3,5,7,13). However, autografts are considered as gold standard of the treatment they are connected with needs of harvesting the bone from other bone source and therefore leads to another surgery, pain, scaring and possible complication during healing.…”

Section: Managementofthebonedefectsmentioning

confidence: 99%

The Osteogenic Potential of Human Nondifferentiated and Pre-differentiated Mesenchymal Stem Cells Combined with an Osteoconductive Scaffold – Early Stage Healing

Tuček

Kočí

Karova

et al. 2017

Acta Med. (Hradec Kralove, Czech Repub.)

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A B ST R AC T Despite the huge research into stem cells and their regenerative properties for bone healing, there are still unanswered questions including the recipient's respond to the presence of the stem cells, the fate of stem cells inside the bone defect and the possible advantage in utilizingpre-differentiatedcells.Toaddresstheseproblems,weusedhumanmultipotentmesenchymalstromal/stemcells(MSCs),GMP Grade,inaratmodelofboneformation.Ina"bioreactorconcept"approachsevenWistarratswereimplantedwith0.2gofsynthetic bonescaffoldseededwith2×106MSCs,sevenWistarratswereimplantedwith0.2gofsyntheticbonescaffoldseededwith1×106pre-differentiatedosteoblastsand1×106pre-differentiatedendothelialcellsand14Wistarratswereimplantedwith0.2gofsyntheticbone scaffoldwithoutseededcellsintoanintramuscularpocketontheleftsideoftheirback.Therightsideofeachratwasusedasacontrol, and0.2gofsyntheticbonescaffoldwasimplantedintotheintramuscularpocketalone.Toseetheearlystagehealingthesampleswere harvested14daysaftertheimplantation,MSCsweredetectedbypositiveDAPIandMTCO2stainingin43%ofallthesamplesimplanted withMSCs,andnoinflammationsignswerepresentinanyimplantedanimal.Newvesselscouldbefoundinbothgroupsimplantedwith MSCs,butnotinthecontrolgroupofanimals.However,hematoxylin-eosinstainingcouldnotdetectnewlycreatedbonewithinthe implantinanyofthegroups.TheseresultswereinlinewithCOLL1staining,wherewecoulddetectpositivestainingonlyinthreecases,all ofwhichwereimplantedwithun-differentiatedMSCs.Accordingtoourfindings,therewerenobenefitsofusingthepre-differentiatedof MSC.

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“…Considering the complication rate of 10-40 % (Arrington et al, 1996;Dimitriou et al, 2011), the limited supply of donor bone (Carragee et al, 2011a) and the significant increase in surgery time associated with bone harvesting (Noshchenko et al, 2014), different approaches are being explored to create bone substitutes which can perform similar or better than autograft bone (Baroli, 2009;Dimitriou et al, 2011). The use of stromal or stem cells (Grayson et al, 2015), growth factors (Gothard et al, 2014) and various biomaterials (Barradas et al, 2011), have shown successful outcomes in animal studies. However, these approaches have not yet reached the clinical practice for widespread use, due to regulatory issues and the difficulty of demonstrating the efficacy of these treatments in clinical studies (Tatara et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Local induction of inflammation affects bone formation

Croes

Kruyt

Loozen

et al. 2017

eCM

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To explore the influence of inflammatory processes on bone formation, we applied a new in vivo screening model. Confined biological pockets were first created in rabbits as a response to implanted bone cement discs. These biomembrane pockets were subsequently used to study the effects of inflammatory stimuli on ectopic bone formation within biphasic calcium phosphate (BCP) constructs loaded with TNF-α, lipopolysaccharide (LPS) or lipoteichoic acid (LTA), all with or without bone morphogenetic protein (BMP)-2. Analysis of bone formation after 12 weeks demonstrated that the inflammatory mediators were not bone-inductive in combination with the BCP alone, but inhibited or enhanced BMP-induced bone formation. LPS was associated with a strong inhibition of bone formation by BMP-2, while LTA and TNF-α showed a positive interaction with BMP-2. Since the biomembrane pockets did not interfere with bone formation and prevented the leakage of pro-inflammatory compounds to the surrounding tissue, the biomembrane model can be used for in vivo approaches to study local inflammation in conjunction with new bone formation. Using this model, it was shown that the modulation of the inflammatory response could be beneficial or detrimental to the subsequent bone formation process. The co-delivery of inflammatory factors and bone-related growth factors should be further explored as a strategy to enhance the bone-forming efficacy of bone substitutes.

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From natural bone grafts to tissue engineering therapeutics: Brainstorming on pharmaceutical formulative requirements and challenges

Cited by 164 publications

References 489 publications

Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds

Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds

The Osteogenic Potential of Human Nondifferentiated and Pre-differentiated Mesenchymal Stem Cells Combined with an Osteoconductive Scaffold – Early Stage Healing

Local induction of inflammation affects bone formation

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