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