@article {19093,
	title = {Biomaterials and Bioactive Agents in Spinal Fusion},
	journal = {Tissue Engineering Part B: Reviews},
	year = {2017},
	month = {2017-05-22 00:00:00},
	publisher = {Mary Ann Liebert},
	abstract = {

Management\  of\  degenerative\  spine\  pathologies\  frequently\  leads\  to\  the\  need\  for\  spinal\  fusion,\  where\ bone\ growth\ is\ induced\ towards\ stabilization\ of\ the\ interventioned\ spine.\ Autologous\ bone\  graft\  (ABG)\  remains\  the\  gold\  standard\  inducer,\  while\  new\  bone\  graft\  substitutes\  attempt\  to\  achieve\ effective\ de\  novo\  bone\  formation\ and\  solid\  fusion.\ Limited\  fusion\ outcomes\  have\ driven\  motivation\  for\  more\  sophisticated\  and\  multidisciplinary\  solutions,\  involving\  new\  biomaterials\  and/or\ biologics,\ through\ innovative\ delivery\ platforms. The\ present\ review\ will\ analyze\ the\ most\  recent\  body\  of\  literature\  focused\  on\  new\  approaches\  for\  consistent\  bone\  fusion\  of\  spinal\  vertebrae,\  including\  the\  development\  of\  new\  biomaterials\  that\  pursue\  physical\  and\  chemical\  aptitudes;\  the\  delivery\  of\ growth\  factors\  (GF)\  to\ accelerate\  new\  bone\  formation;\  and\  the\  use\  of\  cells\ to\ improve\ functional\ bone\ development.\ Bone\ graft\ substitutes\ currently\ in\ clinical\ practice,\  such\ as\ demineralized\ bone\ matrix\ and\ ceramics\ are\  still\ used\ as\  starting\ point\  for\  study\ of\  new\  bioactive\  agents.\  Polyesters\  such\  as\  polycaprolactone\  and\  polylactic\  acid\  arise\  as\  platforms\  for\  development\  of\  composites,\  where\  a\  mineral\  element\  and\  cell/growth\  factors\  constitute\  the\  delivery\ system.\ Exciting\ fusion\ outcomes\ were\ obtained\ in\ several\ small\ and\ large\ animal\ models\  with\  these.\  \  On\  what\  regards\  bioactive\  agents,\  mesenchymal\  stem\  cells,\  preferentially\  derived\  from\ the\ bone\ marrow\ or\ adipose\ tissue,\ were\ studied\ in\ this\ context.\ Autologous\ and\ allogeneic\  approaches,\  as\  well\  as\  osteogenically\  differentiated\  cells,\  have\  been\  tested.\  These\  cell\  sources\  have\  further\  been\  genetically\  engineered\  for\  specific\  growth\  factor\  expression.\  \  Nevertheless,\  results\ on\ fusion\ efficacy\ with\ cells\ have\ been\ inconsistent.\ On\ the\ other\ hand,\ delivery\ of\ growth\  factors\  (most\  commonly\  BMP-2),\  have\  provided\  favorable\  outcomes.\  Complications\  related\  to\  burst\  release\  and\  dosing\  are\  still\  target\  of\  research\  through\  development\  of\  controlled\  release\  systems\ or\ alternative\ GF\ such\ as\ NELL-1,\ Oxysterols\ or\ COMP-Ang1.\ Promising\ solutions\ with\ new\  biomaterial\  and\  GF\  compositions\  are\  becoming\  closer\  to\  the\  human\  patient,\  as\  these\  evidence\  high\  fusion\  performance,\ while\  offering\  cost\ and\  safety\ advantages.\ The\  use\  of\  cells\  has\  not\ yet\  proven\ solid\ benefits,\ whereas\ further\ understanding\ of\ cell\ behavior\ remains\ a\ challenge.\ \ 

}, keywords = {Spinal~fusion, ~Adult~stem~cells, ~Growth~factors, ~Polymeric~scaffolds}, issn = {2152-4947}, doi = {10.1089/ten.TEB.2017.0072}, author = {Duarte, R. M. and Varanda, P. and Reis, R. L. and Duarte, A. R. C. and Correia Pinto, J.} }

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