PLGA Containing Human Adipose-Derived Stem Cell-Derived Extracellular Vesicles Accelerates the Repair of Alveolar Bone Defects via Transfer of CGRP

<div>Promoting effect of hADSC-EVs on the osteogenic differentiation of hPDLSCs in vitro. hPDLSCs cultured in OM were coincubated with EVs (1 <i>μ</i>g/mL or 5 <i>μ</i>g/mL). (a) ALP staining analysis of ALP activity in hPDLSCs (<span class="nowrap"><svg height="12.7373pt" id="M36" style="vertical-align:-3.429399pt" version="1.1" viewbox="-0.0498162 -9.3079 92.068 12.7373" width="92.068pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M319 325C317 349 306 409 297 431C277 440 250 449 209 449C117 449 57 389 57 319C57 243 122 209 182 182C232 159 261 135 261 91C261 48 227 21 190 21C130 21 85 79 68 145L41 140C41 104 51 36 58 22C75 7 121 -12 172 -12C252 -12 337 35 337 126C337 195 286 231 210 262C166 281 126 304 126 348C126 388 152 417 191 417C240 417 274 378 294 318L319 325Z"></path></g><g transform="matrix(.013,0,0,-0.013,4.875,0)"><path d="M390 111C344 68 312 56 269 56C212 56 118 102 118 241C118 346 175 401 241 401C277 401 312 388 342 360C350 352 355 349 361 349C372 349 394 371 394 392C394 403 391 411 378 422C362 436 329 449 288 449H287C250 449 190 432 138 392C71 341 37 274 37 197C37 90 112 -12 238 -12C297 -12 363 32 407 90L390 111Z"></path></g><g transform="matrix(.013,0,0,-0.013,10.414,0)"><path d="M433 39L423 65C413 59 399 54 387 54C370 54 352 69 352 114V299C352 352 342 392 307 422C285 440 255 449 225 449C168 437 102 399 75 379C56 365 44 353 44 339C44 315 69 296 87 296C101 296 111 303 116 319C124 349 133 371 145 385C156 397 171 404 190 404C241 404 275 364 275 291V274C253 256 180 229 120 209C65 190 39 159 39 110C39 47 88 -12 159 -12C189 -12 237 25 277 52C282 35 288 21 301 8C312 -3 333 -12 348 -12L433 39ZM275 84C256 65 221 48 195 48C164 48 124 73 124 124C124 161 146 180 185 198C206 208 254 229 275 240V84Z"></path></g><g transform="matrix(.013,0,0,-0.013,16.186,0)"><path d="M238 0V26C174 32 166 38 166 104V712C132 700 70 683 18 677V653C81 647 87 645 87 577V104C87 38 78 32 15 26V0H238Z"></path></g><g transform="matrix(.013,0,0,-0.013,19.475,0)"><path d="M380 106C343 72 306 56 265 56C195 56 116 112 115 248C235 252 361 262 377 265C396 269 400 277 400 297C400 374 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103V296C732 394 682 449 605 449C576 449 550 437 529 423C504 407 475 389 446 366C425 418 382 449 334 449C303 449 279 437 253 421C222 403 201 385 180 371V452C135 432 85 419 41 411V388C99 379 102 374 102 310V103C102 38 93 32 27 26V0H238V26C189 32 180 38 180 103V338C210 363 250 390 289 390C351 390 377 348 377 275V103C377 37 368 32 306 26V0H520V26C465 32 456 38 456 101V296C456 314 455 326 453 338C491 369 529 390 565 390C628 390 653 345 653 274V107C653 36 642 32 583 26V0H797Z"></path></g></svg>).</span> (b) ARS staining of cellular matrix mineralization in hPDLSCs (<span class="nowrap"><svg height="12.7373pt" id="M37" style="vertical-align:-3.429399pt" version="1.1" viewbox="-0.0498162 -9.3079 92.068 12.7373" width="92.068pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M319 325C317 349 306 409 297 431C277 440 250 449 209 449C117 449 57 389 57 319C57 243 122 209 182 182C232 159 261 135 261 91C261 48 227 21 190 21C130 21 85 79 68 145L41 140C41 104 51 36 58 22C75 7 121 -12 172 -12C252 -12 337 35 337 126C337 195 286 231 210 262C166 281 126 304 126 348C126 388 152 417 191 417C240 417 274 378 294 318L319 325Z"></path></g><g transform="matrix(.013,0,0,-0.013,4.875,0)"><path d="M390 111C344 68 312 56 269 56C212 56 118 102 118 241C118 346 175 401 241 401C277 401 312 388 342 360C350 352 355 349 361 349C372 349 394 371 394 392C394 403 391 411 378 422C362 436 329 449 288 449H287C250 449 190 432 138 392C71 341 37 274 37 197C37 90 112 -12 238 -12C297 -12 363 32 407 90L390 111Z"></path></g><g transform="matrix(.013,0,0,-0.013,10.414,0)"><path d="M433 39L423 65C413 59 399 54 387 54C370 54 352 69 352 114V299C352 352 342 392 307 422C285 440 255 449 225 449C168 437 102 399 75 379C56 365 44 353 44 339C44 315 69 296 87 296C101 296 111 303 116 319C124 349 133 371 145 385C156 397 171 404 190 404C241 404 275 364 275 291V274C253 256 180 229 120 209C65 190 39 159 39 110C39 47 88 -12 159 -12C189 -12 237 25 277 52C282 35 288 21 301 8C312 -3 333 -12 348 -12L433 39ZM275 84C256 65 221 48 195 48C164 48 124 73 124 124C124 161 146 180 185 198C206 208 254 229 275 240V84Z"></path></g><g transform="matrix(.013,0,0,-0.013,16.186,0)"><path d="M238 0V26C174 32 166 38 166 104V712C132 700 70 683 18 677V653C81 647 87 645 87 577V104C87 38 78 32 15 26V0H238Z"></path></g><g transform="matrix(.013,0,0,-0.013,19.475,0)"><path d="M380 106C343 72 306 56 265 56C195 56 116 112 115 248C235 252 361 262 377 265C396 269 400 277 400 297C400 374 333 449 250 449H249C198 449 144 421 103 376S37 269 37 201C37 88 109 -12 232 -12C263 -12 332 6 395 84L380 106ZM225 412C281 412 315 364 314 312C314 297 308 292 290 292C232 290 176 289 120 289C135 370 180 412 225 412Z"></path></g><g transform="matrix(.013,0,0,-0.013,27.268,0)"><path d="M152 404V712C115 698 54 683 7 677V654C71 648 73 642 73 579V24C128 -2 179 -12 220 -12C353 -12 471 92 471 238C471 357 381 449 274 449C262 449 249 446 233 439L152 404ZM152 374C170 384 202 393 230 393C313 393 382 326 382 213C382 97 330 26 246 26C194 26 165 62 158 81C154 91 152 101 152 116V374Z"></path></g><g transform="matrix(.013,0,0,-0.013,33.937,0)"><path d="M433 39L423 65C413 59 399 54 387 54C370 54 352 69 352 114V299C352 352 342 392 307 422C285 440 255 449 225 449C168 437 102 399 75 379C56 365 44 353 44 339C44 315 69 296 87 296C101 296 111 303 116 319C124 349 133 371 145 385C156 397 171 404 190 404C241 404 275 364 275 291V274C253 256 180 229 120 209C65 190 39 159 39 110C39 47 88 -12 159 -12C189 -12 237 25 277 52C282 35 288 21 301 8C312 -3 333 -12 348 -12L433 39ZM275 84C256 65 221 48 195 48C164 48 124 73 124 124C124 161 146 180 185 198C206 208 254 229 275 240V84Z"></path></g><g transform="matrix(.013,0,0,-0.013,39.527,0)"><path d="M181 342V451C133 431 89 419 40 411V388C98 381 102 377 102 311V104C102 38 95 32 33 26V0H263V26C186 32 181 38 181 104V287C203 343 235 372 261 372C277 372 289 366 304 352C310 346 318 345 330 350C349 359 362 379 362 399C362 422 338 449 304 449C256 449 213 393 183 342H181Z"></path></g><g transform="matrix(.013,0,0,-0.013,48.046,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,59.309,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"></path></g><g transform="matrix(.013,0,0,-0.013,65.549,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,73.964,0)"><path d="M538 96L524 119C492 88 454 63 446 63C439 63 434 70 440 101C463 223 491 341 518 448H508L433 422L401 276C355 192 240 56 188 56C163 56 154 89 163 133C184 233 207 338 235 443L230 448L152 424L58 17C40 -60 23 -143 23 -185C23 -241 42 -261 63 -261C92 -261 117 -241 125 -227L124 -221C109 -209 89 -165 89 -103C89 -55 96 -13 105 26H107C121 -3 134 -12 151 -12C172 -12 194 -5 221 16C279 61 330 124 384 194H386C381 159 377 141 368 105C343 3 363 -12 383 -12C416 -12 486 35 538 96Z"></path></g><g transform="matrix(.013,0,0,-0.013,81.18,0)"><path d="M797 0V26C739 32 732 36 732 103V296C732 394 682 449 605 449C576 449 550 437 529 423C504 407 475 389 446 366C425 418 382 449 334 449C303 449 279 437 253 421C222 403 201 385 180 371V452C135 432 85 419 41 411V388C99 379 102 374 102 310V103C102 38 93 32 27 26V0H238V26C189 32 180 38 180 103V338C210 363 250 390 289 390C351 390 377 348 377 275V103C377 37 368 32 306 26V0H520V26C465 32 456 38 456 101V296C456 314 455 326 453 338C491 369 529 390 565 390C628 390 653 345 653 274V107C653 36 642 32 583 26V0H797Z"></path></g></svg>).</span> (c) Expression of RUNX2, ALP, and OCN determined by RT-qPCR in hPDLSCs. (d) Western blot analysis of RUNX2, ALP, and OCN proteins in hPDLSCs. <span class="nowrap"><svg height="13.532pt" id="M38" style="vertical-align:-3.4295pt" version="1.1" viewbox="-0.0498162 -10.1025 50.6052 13.532" width="50.6052pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 470C289 461 271 442 262 422C281 372 287 345 290 288C243 319 222 338 189 380C167 381 142 376 125 366C125 347 133 322 145 304C198 296 225 288 275 262C225 236 198 227 145 220C133 201 125 177 126 158C141 148 167 143 189 144C222 186 243 205 290 236C288 179 282 152 262 102C272 82 289 63 306 54C322 63 340 82 350 102C330 152 324 179 321 236C368 205 390 186 422 144C444 143 470 148 486 158Z"></path></g><g transform="matrix(.013,0,0,-0.013,6.079,0)"><path d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"></path></g><g transform="matrix(.013,0,0,-0.013,17.421,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"></path></g><g transform="matrix(.013,0,0,-0.013,28.684,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,34.924,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,37.888,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,44.128,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"></path></g></svg>,</span> compared with hPDLSCs cultured in PM. #<span class="nowrap"><svg height="11.7782pt" id="M39" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 44.5261 11.7782" width="44.5261pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"></path></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"></path></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"></path></g></svg>,</span> compared with hPDLSCs cultured in OM, <span class="nowrap"><svg height="8.8423pt" id="M40" style="vertical-align:-0.2064009pt" version="1.1" viewbox="-0.0498162 -8.6359 32.2343 8.8423" width="32.2343pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g 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Oxidative Medicine and Cellular Longevity

fig3

Figure 3

Figure 3: PLGA Containing Human Adipose-Derived Stem Cell-Derived Extracellular Vesicles Accelerates the Repair of Alveolar Bone Defects via Transfer of CGRP 

Figure 3 | PLGA Containing Human Adipose-Derived Stem Cell-Derived Extracellular Vesicles Accelerates the Repair of Alveolar Bone Defects via Transfer of CGRP 