Bones_NN2 often_RR come_VV0 in_II complex_NN1 ,_, delicate_JJ shapes_NN2 ,_, making_VVG it_PPH1 hard_RR to_TO find_VVI matching_JJ natural_JJ replacements_NN2 for_IF them_PPHO2 in_II patients_NN2 suffering_VVG from_II injuries_NN2 ,_, diseases_NN2 or_CC birth_NN1 defects_NN2 ._. 
Now_RT researchers_NN2 have_VH0 grown_VVN bone_NN1 grafts_VVZ in_II the_AT exact_JJ shape_NN1 of_IO a_AT1 desired_JJ bone_NN1 ,_, an_AT1 advance_NN1 that_CST could_VM help_VVI provide_VVI doctors_NN2 with_IW just_RR what_DDQ they_PPHS2 need_VV0 for_IF face_NN1 ,_, skull_NN1 and_CC other_JJ skeletal_JJ reconstructions_NN2 ._. 
Although_CS missing_JJ bone_NN1 can_VM be_VBI replaced_VVN by_II titanium_NN1 ,_, "_" there_EX is_VBZ no_AT better_JJR substitute_NN1 for_IF lost_JJ tissue_NN1 than_CSN living_JJ tissue_NN1 ,_, "_" bioengineer_VV0 Gordana_NP1 Vunjak-Novakovic_NN1 at_II Columbia_NP1 University_NN1 explains_VVZ ._. 
"_" Although_CS titanium_NN1 is_VBZ better_JJR than_CSN nothing_PN1 --_JJ you_PPY need_VV0 something_PN1 to_TO help_VVI bear_NN1 loads_NN2 --_JJ real_JJ bones_NN2 also_RR have_VH0 bone_NN1 marrow_NN1 inside_II that_DD1 has_VHZ many_DA2 important_JJ metabolic_JJ functions_NN2 ._. "_" 
Patients_NN2 also_RR could_VM rely_VVI on_II donated_JJ bones_NN2 ,_, but_CCB these_DD2 run_VV0 the_AT risk_NN1 of_IO contamination_NN1 and_CC tissue_NN1 rejection_NN1 ._. 
Or_CC surgeons_NN2 can_VM harvest_VVI bone_NN1 from_II elsewhere_RL in_II a_AT1 patient_NN1 's_GE body_NN1 and_CC carve_VV0 it_PPH1 to_TO fit_VVI where_RRQ they_PPHS2 need_VV0 to_TO ,_, "_" but_CCB this_DD1 is_VBZ very_RG hard_JJ on_II patients_NN2 ,_, "_" Vunjak-Novakovic_NN1 says_VVZ ._. 
"_" The_AT damage_NN1 at_II the_AT site_NN1 of_IO harvest_NN1 is_VBZ major_JJ ,_, and_CC it_PPH1 takes_VVZ long_RR to_TO regenerate_VVI this_DD1 tissue_NN1 ,_, and_CC patients_NN2 often_RR report_VV0 doing_VDG so_RR hurts_VVZ much_DA1 more_DAR and_CC longer_RRR than_CSN the_AT implant_NN1 itself_PPX1 ._. "_" 
Instead_RR ,_, bioengineer_VV0 Warren_NP1 Grayson_NP1 ,_, along_II21 with_II22 Vunjak-Novakovic_NN1 and_CC their_APPGE colleagues_NN2 ,_, grew_VVD their_APPGE own_DA grafts_NN2 ._. 
They_PPHS2 started_VVD with_IW the_AT temporomandibular_JJ joint_JJ ,_, found_VVN at_II the_AT point_NN1 where_RRQ the_AT jaw_NN1 meets_VVZ the_AT skull_NN1 in_II31 front_II32 of_II33 the_AT ear_NN1 ._. 
"_" It_PPH1 was_VBDZ the_AT greatest_JJT challenge_NN1 we_PPIS2 could_VM think_VVI of_IO ,_, the_AT most_RGT complex_JJ piece_NN1 in_II the_AT skull_NN1 in_II31 terms_II32 of_II33 shape_NN1 ,_, based_VVN on_II surgeons_NN2 we_PPIS2 asked_VVD ,_, "_" she_PPHS1 says_VVZ ._. 
"_" If_CS we_PPIS2 can_VM grow_VVI this_DD1 piece_NN1 ,_, we_PPIS2 think_VV0 we_PPIS2 can_VM grow_VVI anything_PN1 ._. "_" 
The_AT temporomandibular_JJ joint_JJ ,_, or_CC TMJ_NP1 ,_, is_VBZ also_RR of_IO growing_JJ clinical_JJ relevance_NN1 ,_, Vunjak-Novakovic_NN1 adds_VVZ ._. 
As_RG many_DA2 as_CSA roughly_RR one_MC1 out_RP of_IO four_MC people_NN experience_VV0 symptoms_NN2 of_IO disorders_NN2 involving_VVG the_AT TMJ_NP1 ,_, such_II21 as_II22 pain_NN1 in_II the_AT chewing_JJ muscles_NN2 and_CC jaw_NN1 stiffness_NN1 as_II31 well_II32 as_II33 painful_JJ clicking_NN1 ,_, popping_VVG or_CC grating_JJ in_II the_AT joint_JJ ._. 
The_AT researchers_NN2 first_MD used_JJ real_JJ bone_NN1 as_II a_AT1 scaffold_NN1 --_NN1 "_" we_PPIS2 know_VV0 actual_JJ bones_NN2 are_VBR ideal_JJ because_CS they_PPHS2 work_VV0 in_II real_JJ life_NN1 ,_, "_" Vunjak-Novakovic_NN1 says_VVZ ._. 
They_PPHS2 stripped_VVD the_AT knee_NN1 joints_NN2 of_IO calves_NN2 of_IO all_DB their_APPGE cells_NN2 with_IW detergents_NN2 and_CC enzymes_NN2 and_CC then_RT ,_, based_VVN on_II digitized_JJ x-ray_JJ images_NN2 from_II an_AT1 anonymous_JJ patient_NN1 ,_, had_VHD machines_NN2 carve_VVI them_PPHO2 into_II cubic-centimeter-size_JJ human_JJ jaw_NN1 joints_NN2 ._. 
They_PPHS2 next_MD seeded_VVD each_DD1 scaffold_NN1 with_IW three_MC million_NNO commercially_RR available_JJ human_JJ mesenchymal_JJ stem_NN1 cells_NN2 ,_, which_DDQ can_VM give_VVI rise_NN1 to_II bone_NN1 ,_, cartilage_NN1 ,_, fat_JJ and_CC other_JJ tissues_NN2 ._. 
The_AT cells_NN2 ,_, which_DDQ lined_VVD the_AT pores_NN2 of_IO the_AT scaffold_NN1 ,_, were_VBDR regularly_RR fed_VVN with_IW streams_NN2 of_IO nutrients_NN2 ,_, growth_NN1 factors_NN2 and_CC oxygen_NN1 in_II a_AT1 bioreactor_NN1 ._. 
The_AT pattern_NN1 and_CC rate_NN1 of_IO this_DD1 perfusion_NN1 guides_NN2 how_RRQ the_AT bone_NN1 structure_NN1 grows_VVZ ,_, just_RR as_CSA blood_NN1 does_VDZ in_RR21 vivo_RR22 ,_, and_CC the_AT physical_JJ stimulation_NN1 of_IO the_AT cells_NN2 provided_VVN by_II this_DD1 flow_NN1 is_VBZ critical_JJ for_IF proper_JJ growth_NN1 ._. 
"_" If_CS you_PPY use_VV0 conventional_JJ tissue_NN1 culture_NN1 techniques_NN2 without_IW this_DD1 perfusion_NN1 ,_, you_PPY end_VV0 up_RP with_IW something_PN1 like_II a&lsqb;n&rsqb;_JJ M_NN1 &M;_NULL candy_NN1 --_NN1 &lsqb;_( a_AT1 joint_JJ with_IW &rsqb;_) a_AT1 healthy_JJ surface_NN1 ,_, but_CCB dead_RG inside_RL ,_, "_" Vunjak-Novakovic_NN1 says_VVZ ._. 
After_II five_MC weeks_NNT2 of_IO cultivation_NN1 ,_, cell_NN1 numbers_NN2 increased_VVN up_II21 to_II22 75-fold_JJ ,_, and_CC the_AT researchers_NN2 saw_VVD functional_JJ bone_NN1 tissue_NN1 form_NN1 ._. 
"_" It_PPH1 's_VBZ a_AT1 stellar_JJ piece_NN1 of_IO work_NN1 --_NN1 the_AT fact_NN1 they_PPHS2 were_VBDR able_JK to_TO achieve_VVI the_AT precise_JJ shape_NN1 they_PPHS2 need_VV0 is_VBZ impressive_JJ ,_, "_" says_VVZ Charles_NP1 Vacanti_NP1 ,_, director_NN1 of_IO the_AT Laboratory_NN1 for_IF Tissue_NN1 Engineering_NN1 and_CC Regenerative_JJ Medicine_NN1 at_II Brigham_NP1 and_CC Women_NN2 's_GE Hospital_NN1 in_II Boston_NP1 ,_, who_PNQS did_VDD not_XX take_VVI part_NN1 in_II this_DD1 research_NN1 ._. 
Other_JJ research_NN1 teams_NN2 had_VHD tried_VVN developing_JJ replacements_NN2 for_IF this_DD1 joint_JJ ,_, but_CCB could_VM only_RR develop_VVI simple_JJ or_CC imprecise_JJ shapes_NN2 or_CC grow_VVI the_AT bone_NN1 tissue_NN1 inside_II mice_NN2 ,_, a_AT1 concept_NN1 that_CST works_VVZ well_RR for_IF research_NN1 purposes_NN2 but_CCB not_XX for_IF human_JJ applications_NN2 ,_, because_CS cells_NN2 and_CC molecules_NN2 from_II the_AT mouse_NN1 's_GE body_NN1 could_VM contaminate_VVI the_AT implant_NN1 ,_, and_CC only_RR very_RG small_JJ bones_NN2 could_VM be_VBI grown_VVN ._. 
"_" This_DD1 is_VBZ the_AT first_MD anatomically_RR shaped_JJ piece_NN1 of_IO fully_RR viable_JJ human_JJ bone_NN1 ,_, "_" Vunjak-Novakovic_NN1 says_VVZ ._. 
"_" It_PPH1 's_VBZ important_JJ that_CST it_PPH1 all_DB be_VBI viable_JJ --_NN1 if_CS not_XX ,_, not_XX only_JJ might_NN1 cells_NN2 die_VVI in_II the_AT center_NN1 of_IO the_AT graft_NN1 ,_, but_CCB they_PPHS2 can_VM release_VVI bad_JJ signals_NN2 to_II remaining_VVG healthy_JJ cells_NN2 in_II an_AT1 'apoptotic_JJ cascade_NN1 ,_, '_GE essentially_RR saying_VVG ,_, 'Conditions_NN2 are_VBR horrible_JJ ,_, let_VM21 's_VM22 commit_VVI suicide_NN1 ._. '_" "_" 
In_II the_AT future_NN1 the_AT researchers_NN2 see_VV0 using_VVG stem_NN1 cells_NN2 taken_VVN from_II patients_NN2 to_TO grow_VVI new_JJ bones_NN2 ._. 
"_" One_MC1 potential_JJ source_NN1 is_VBZ bone_NN1 marrow_NN1 ,_, which_DDQ we_PPIS2 used_VVD in_II this_DD1 study_NN1 ,_, but_CCB liposuction_NN1 can_VM also_RR be_VBI used_JJ --_NN1 you_PPY can_VM take_VVI fat_NN1 from_II the_AT body_NN1 ,_, get_VV0 rid_VVN of_IO the_AT fat_JJ cells_NN2 ,_, and_CC then_RT you_PPY 're_VBR left_VVN with_IW nice_JJ immature_JJ mesenchymal_JJ stem_NN1 cells_NN2 ,_, but_CCB in_II much_RR larger_JJR numbers_NN2 than_CSN in_II bone_NN1 marrow_NN1 ,_, "_" Vunjak-Novakovic_NN1 explains_VVZ ._. 
Also_RR ,_, instead_II21 of_II22 relying_VVG on_II actual_JJ bone_NN1 as_II a_AT1 scaffold_NN1 ,_, they_PPHS2 are_VBR now_RT working_VVG with_IW synthetic_JJ mineralized_JJ protein_NN1 ,_, which_DDQ they_PPHS2 can_VM better_RRR mold_VVI and_CC control_VVI ._. 
One_MC1 major_JJ concern_NN1 ,_, Vacanti_JJ notes_NN2 ,_, is_VBZ ensuring_VVG that_DD1 bone_NN1 cells_NN2 survive_VV0 once_RR the_AT graft_NN1 is_VBZ implanted_VVN ._. 
Vunjak-Novakovic_NN1 says_VVZ the_AT researchers_NN2 are_VBR now_RT determining_VVG how_RRQ best_RRT to_TO grow_VVI blood_NN1 vessels_NN2 in_II bone_NN1 grafts_VVZ that_CST can_VM keep_VVI them_PPHO2 alive_JJ ._. 
Bioengineer_VV0 David_NP1 Kaplan_NP1 at_II Tufts_NN2 University_NN1 's_GE Department_NN1 of_IO Biomedical_JJ Engineering_NN1 ,_, who_PNQS had_VHD no_AT role_NN1 in_II these_DD2 findings_NN2 ,_, calls_VVZ the_AT work_NN1 "_" fantastic_JJ "_" and_CC adds_VVZ future_JJ research_NN1 might_VM want_VVI the_AT bioreactor_NN1 to_TO mimic_VVI the_AT same_DA range_NN1 of_IO mechanical_JJ forces_NN2 this_DD1 bone_NN1 will_VM see_VVI if_CSW implanted_JJ --_NN1 for_REX21 instance_REX22 ,_, for_IF the_AT jaw_NN1 joint_NN1 ,_, "_" you_PPY 'd_VM want_VVI it_PPH1 to_TO experience_VVI compression_NN1 and_CC torsion_NN1 ._. "_" 
Grayson_NN1 ,_, Vunjak-Novakovic_JJ and_CC their_APPGE colleagues_NN2 reported_VVD their_APPGE findings_NN2 online_JJ October_NPM1 5_MC in_II the_AT Proceedings_NN2 of_IO the_AT National_JJ Academy_NN1 of_IO Sciences_NN2 ._. 
