Ọgba aghara Ụzọ atọ dị n'azụ imepụta Peptide Hydrogel Multifunctional
Chee echiche banyere peptide hydrogel dị ka ihe nhụcha mkpụrụ ndụ nwere ihe atọ chọrọ. Ọ ghaghị jidesie ike n'elu ndu ma ọ bụ anụ ahụ, nke na-apụtakarị ikpughe ụdị ebubo ebubo ma ọ bụ njirimara na interface. Ọ ghaghị igbu ma ọ bụ gbochie ụmụ nje, nke na-adabere na cationic na hydrophobic residues nke na-akpaghasị membranes nje. Ọ ghaghịkwa nọrọ jụụ - dị ka gel n'okpuru physiological ọnọdụ, na dị ka ngwaahịa na shelf.
Ihe isi ike bụ na onye ọ bụla na-arụ ọrụ na-atụgharị na igwe mgbakọ na-eme ka peptide bụrụ gel na mbụ. Motifs adhesion dị ka RGD bụ hydrophilic na polar, ma gelation na-eme nke ọma na nkwakọ ngwaahịa hydrophobic na nchịkọta aromatic. Mgbochi mgbochi na-ebu njupụta ụgwọ dị elu nke na-eme ka mmekọrịta akpụkpọ ahụ dịkwuo mma mana ọ nwekwara ike ịkpalite nchịkọta na-enweghị isi.. Dị ka sara mbara reviews nke multifunctional onwe-agbakọta peptide hydrogels ndetu, kemịkalụ iwebata oke ọrụ biofunctionality na-akpaghasị mgbakọ, gelation, ma ọ bụ arụ ọrụ igwe - ihe ndị na-eme ka ihe eji eme ihe.
Ụzọ mgbapụ na-adịkarị bụ modularity: kewaa peptide n'ime ngalaba na-agbakọta onwe ya na ihe dị iche iche bioactive motif, kama ịnwa ịkwanye ọrụ ọ bụla n'ime otu yinye apịaji. Nyocha na na-akwakọta peptide hydrogels nke nwere antimicrobial ma ọ bụ ihe nrapado cell. na-egosi na ijikọ isi mkpokọta onwe ya na RGD etinyere ma ọ bụ ebumnuche sitere na lactoferrin nwere ike ichekwa gelation mgbe ị na-egosipụta ọrụ ahụ.. Ịgwakọta RGD hydrophilic dị ukwuu na gelator siri ike dị ka Fmoc-diPhe na-eme ka netwọk ahụ guzosie ike kama ibibi ya..
The takeaway: na-emeso adhesion, antimicrobial edinam, na nkwụsi ike dị ka ihe jikọtara ọnụ, ọbụghị njiri mara onwe. Mgbanwe ọ bụla n'otu na-agbanwe ndị ọzọ, na imewe modular bụ usoro nchebe mbụ gị megide njikọ ahụ. Inweta nguzozi a nke ọma bụ ihe kacha mkpa multifunctional peptide hydrogel imewe.
Usoro nhazi: Ebe Ọrụ Na-asọmpi n'otu Chain
Usoro nhazi bụ ebe ọtụtụ hydrogels multifunctional na-aga nke ọma ma ọ bụ daa tupu otu mmeghachi omume njikọ. Usoro amino-acid nke peptide na-edozi nguzozi hydrophobic-hydrophilic, nkesa ụgwọ, yana geometry mbukota nke na-ekpebi ma β-sheet nyere iwu, hydrogen-njikọ, na ihe owuwu na-esi ísì ụtọ na-etolite.
Isi nkwekọrịta dị n'etiti ngosi elu na isi kwụsie ike. Adhesion motifs ga-anọgide na-enweta na interface gel, ma ọ bụrụ na ha dị oke hydrophilic ma ọ bụ dị oke oke, ha nwere ike ibuli mkpokọta mgbakọ dị egwu ma mee ka gelation ghara iru. Ihe mgbochi nje chọrọ lysine na arginine zuru ezu iji mekọrịta ihe na akpụkpọ ahụ, mana njupụta ụgwọ dị elu na-abawanye mmekọrịta na-enweghị isi nke na-agbanwe otú peptides si abịa.
Arụ ọrụ heuristics na-adị ndụ n'ịkwalite elu:
- Nyochaa usoro n'isi maka ịgba ọsọ hydrophobic, ụgwọ net, na mkpokọta ihe ize ndụ tupu ime njikọ. Ogologo ogologo na-adịghị agbaji agbaji na-ebu amụma ma nchịkọta resin n'oge nhazi usoro siri ike yana ngwaahịa mmiri na-adịghị edozi..
- Ebe ebubo ebubo ma ọ bụ nnukwu ọrụ na njedebe karia n'etiti nzuko nke onwe. Termini na-anabata mkpado hydrophilic na-emebighị isi nkwakọ ngwaahịa.
- Ọrụ dị iche iche n'ime usoro - akụkụ "onye nrụpụta" na-eme mgbakọ ebe akụkụ "binder/killer" na-arụ ọrụ ahụ.. Modulity a bụ otu ụkpụrụ a na-ekegharịkarị n'akwụkwọ.
- Tụgharịa njupụta ụgwọ ụma ụma. Ego zuru oke maka mmebi akpụkpọ ahụ, mana ọ bụghị nke ukwuu na elu ahụ gbakọtara na-esiwanye ike site na mmetụta mgbochi nke bioactivity ma ọ bụ injectability na-eweda ala..
N'ihi na ndị a heuristics na-adabere na-adị ọcha a haziri usoro nwere ike n'ezie wuo, ha nọ n'akụkụ-na-akụkụ na a ezi ntule nke omenala peptide njikọ enwere ike - usoro nchịkọta-adịkarị mfe ma ọ bụ multi-disulfide nke na-agbakọta na amụma nwere ike ịdaba na resin ogologo oge tupu ya erute nyocha cell gị..
Heuristics ndị a dị mkpa n'ihi na usoro na-agbakọta mara mma na 5 mg/ml nwere ike daa na nhazi-dị mkpa, ma ọ bụ hapụ ngwọta kpamkpam otu ugboro, nnu buffer, na pH nke ngwa ikpeazụ ewebata.
Mgbanwe Saịtị akọwapụtara: Nhọrọ bụ ọkpọ ọkpọ
Ọtụtụ hydrogels na-arụ ọrụ anaghị adabere naanị na amino acid eke. Phosphorylation, acetylation, PEGylation, stapling, ịgba ígwè, na crosslinking ejiri niile iji wụnye nkwụsi ike ma ọ bụ bioactivity. Nsogbu bụ na "tinye mgbanwe" dị mfe na akwụkwọ karịa na reactor.
Ihe ịma aka etiti bụ saịtị-nhọpụta. Ịkpọ aha lysine ma ọ bụ cysteine n'enweghị ihe ọ bụla na-emepụta conjugates dị iche iche ma na-ebelata ọrụ ma ọ bụ gbanwee nhazi peptide.. Dị ka ntuziaka onye kemist maka ngbanwe peptide pụrụ iche na-eme ka o doo anya, ọbụna ọkpụkpụ azụ nke ahọpụtara saịtị ma ọ bụ mgbanwe n'akụkụ nwere ike ịgbanwe nhazi nke abụọ, solubility, na nchịkọta - nke na-azụ azụ ozugbo n'ime ka peptide si agbakọta n'ime gel. Ọnọdụ mmeghachi omume dịkwa mkpa: chemistry na-achọ okpomọkụ, ìhè, ma ọ bụ ibelata ndị ọrụ nwere ike denature ngalaba-encapsulated protein ma ọ bụ imerụ ndụ mkpụrụ ndụ na scaffold.
Maka onye nrụpụta, nke a pụtara ịhọrọ mgbanwe ọ bụghị naanị maka kemistri ya mana maka ya orthogonality na processability. Ịchọrọ aka nke na-emeghachi omume n'otu ihe fọdụrụ akọwapụtara, na-anabata ihe nchekwa mmiri, ma ghara imebi isi mgbakọ. PEG ma ọ bụ solubilizing spacers etinyere na njedebe nwere ike ibelata mmekọrịta na-enweghị isi ma melite nkwụsi ike, mana over-PEGylation nwere ike zoo ebumnuche na-arụ ọrụ. Ihe mmụta bara uru bụ na n'ezie hydrogel multifunctional na-abụkarị Pọtụfoliyo nke mgbanwe saịtị akọwapụtara nke ọma dị ka ihe wuo ya zuru oke - ọ bụghị peptide efu yana otu arụrụ arụ ọrụ..
Mgbe usoro chọrọ ọtụtụ aka ndị a n'otu oge, uru nke onye mmekọ njikọ na ngwa ngwa mgbanwe miri emi na-aghọ ihe a na-ahụ anya. Onye na-enye ọrụ na-arụ ọrụ mgbe niile mgbagwoju peptide njikọ na mgbanwe gafee ọtụtụ narị ọrụ otu - stapling, Multi-disulfide loops, lipidation, Otu ụzọ FRET - nwere ike imebi nzọụkwụ na-ebuli ọtụtụ ihuenyo ụlọ.
Crosslinking na Mechanics: Nkwụsi ike bụ ihe onwunwe
Peptide Synthesis Akọwapụtaghị nkwụsi ike na peptide hydrogel naanị site na ọkara ndụ kemịkalụ peptide; ọ bụ ihe onwunwe nke netwọk gbakọtara. Atụmatụ njikọ na-ekpebi ma ihe ahụ na-ejide ọdịdị ya, eguzogide dilution, ma na-ahapụ ya na nhazi oge.
Covalent crosslinking na immobilization n'ozuzu merie na anwụ ngwa ngwa. Na-arụ ọrụ na antimicrobial peptide-arụ ọrụ hydrogels chọpụtara na peptides antimicrobial jikọtara ọnụ anaghị apụta na gel ọbụlagodi izu ole na ole ịsachara., idobe ọrụ mpaghara na ogologo ndụ. Azụmahịa-apụ bụ ngagharị: ebumnobi nwere njikọ siri ike nwere ike ọ gaghị eru ebumnuche nje bacteria ma ọ bụ cellular ya n'efu.
Mgbakọ onwe onye na-enweghị mmasị na-emeri na injectability, ọgwụgwọ onwe, na nzaghachi siri ike - ihe ndị dị mkpa maka sirinji-injectable ma ọ bụ nke nwere ike ime mgbanwe. Ọ na-efunahụ ike: gels ndị a na-agbakọta n'ụzọ anụ ahụ na-adị mfe karị na dilution, nnu, pH mgbanwe, na enzymatic ọgụ ozugbo etinyere na physiological gburugburu ebe obibi.
Nyocha nke antimicrobial peptide hydrogels mebe nke a ka ntọhapụ-na-ejigide ahia-apụ. Gel nke na-ahapụ peptide ya na-alụso nje bacteria ọgụ n'ebe dị anya ma nwee ike igbochi uto planktonic ma ọ bụ biofilms.; jel nke na-emebi peptide ya na-enyekarị egbu egbu na mgbochi. Ọ dịghịkwa njọ - nhọrọ ziri ezi dabere ma ebumnuche ọ bụ mgbakwasa ọnya, ihe mkpuchi implant, ma ọ bụ akpụkpọ anụ.
N'okpuru ihe a niile bụ mechanics-biology njikọ. Ihe nguzozi hydrophobic/hydrophilic nke peptide na-achịkwa njupụta nanofiber na nkwụsi ike nke njikọ hydrogen., nke n'aka nke na-esetịpụ porosity, nri njem, na hapụ kinetics. Ịkwalite njupụta crosslink na-abawanye modul nchekwa, mana netwọk nwere njikọ gafere na-aghọ nke na-akụkụ, na-ebelata mgbasa, na ike zoo adhesion ligands. Moduli nchekwa na ọnwụ (G na G″) si rheology bụghị ịchọ mma nọmba - ha bụ readout nke ma gị imewe ebumnobi lanarị mgbakọ.
Omume mmebi iwu: Ịhazi ndụ ihe onwunwe
Nbibi bụ njirimara, ọ bụghị ọnọdụ ọdịda, ma a ghaghị ịchịkwa ya. Enwere ike imezi nguzogide protease site na D-amino acid, ịgba ígwè, PEGylation, ma ọ bụ lipidation - mgbanwe na-emeziwanye nkwụsi ike nhazi na, n'ọnọdụ ụfọdụ, Njirimara antibiofilm. Ọnụ ego ya bụ na nkwụsi ike nke ukwuu nwere ike mebie bioactivity site n'ịkpọchi conformation na-arụ ọrụ nke ọma..
Ngalaba mmebi iwu abụọ chọrọ nlebara anya dị iche iche:
- Nbibi n'ime-vivo. A na-amachikarị peptide hydrogels site na enweghị ntụkwasị obi dabere na pH na mmebi enzymatic na gburugburu physiological., nke na-egbochi ịba uru ụlọ ọgwụ. Ọ bụrụ na gel ga-anọgidesi ike na-eduzi mmụgharị anụ ahụ, Ya hydrolysis na proteolysis ọnụego kwesịrị ka e mere na tụọ, echeghị.
- Nkwụsi ike shelf. Ihe na-arụ ọrụ otu ugboro mana enweghị ike ịlanarị nchekwa bụ ọchịchọ ịmata ihe, ọ bụghị ngwaahịa. Ọnọdụ Lyophilization, ihe fọdụrụ mmiri, na counter-ion ọdịnaya niile mgbanwe ogologo oge kwụsie ike na reproducibility. Maka otu ogbe emeziri ka ọ daa n'usoro, parampat nchekwa na-aghọ ntọhapụ-dị mkpa àgwà àgwà.
Nkwekọrịta ogbe: Mmegharị bụ ezigbo ngwaahịa
Ị nwere ike chepụta hydrogel multifunctional zuru oke otu ugboro. Ịmegharị ya n'ofe batches bụ ọzụzụ dị iche, na ọ bụ ebe ọtụtụ mmemme kwụsịrị n'ụzọ nke ụlọ ọgwụ ma ọ bụ azụmahịa.
Ihe mmalite peptide dị ọcha bụ ọ dị mkpa mana ezughị oke. Gelation na akụrụngwa ikpeazụ na-enwe mmetụta dị ukwuu maka nhazi mgbanwe - mkpokọta peptide, ihe nchekwa, pH, ike ionic, okpomọkụ, Ịgwakọta usoro, na oge ịka nká. N'ọtụtụ buru ibu, nsogbu ịgwakọta na thermal gradients na-emepụta mpaghara nwụrụ anwụ na njikọ na-enweghị isi, nke nwere ike iwepụta mgbanwe oghere na isi ike na ọzịza n'ime otu ogbe. Ngwakọta nke siri ike n'onwe ya na-eburu nhụsianya batch nke ya: resin tupu ọzịza, njikọ njikọ, na-asa mpịakọta, ọnọdụ nkwụsịtụ, usoro mmiri ozuzo, na nhazi lyophilization niile nwere ike gbanwee profaịlụ adịghị ọcha na ọdịnaya mmiri n'etiti nza.
Azịza ya bara uru bụ ịkọwa àgwà dị oke egwu (Ndị CQA) ma kpọchie ogwe ntọhapụ gburugburu ha. Nke a pụtara ịhazi akụrụngwa akụrụngwa, na-edozi gelation SOP, na ijide ogbe ọ bụla ka edobere windo nnabata maka modulus, morphology, na ọrụ - anaghị ahapụ ya na ịdị ọcha HPLC naanị. Ọ bụkwa ebe mmepụta gburugburu ebe obibi na-aghọ nkọwa kama ọ bụ nkọwa ala ala peeji: nrụpụta na a sterile klaasị 100 mmepụta ihe owuwu na-ewepu particulates, ibu ibu, na endotoxin dị ka mgbanwe ndị a na-achịkwaghị achịkwa nke ga-egosipụta ma ọ bụghị dị ka ihe nrịba nke batch-to-batch na cell na in-vivo assays.. Mkpebi nrụpụta nke dị ka akwụkwọ akụkọ na bench ụlọ nyocha - njikwa usoro, nchịkọta orthogonal, usoro ndị a na-ahụkarị - bụ kpọmkwem ihe na-ekewa gel a na-ebipụta na ihe a na-emepụtagharị.
Nnwale na-ekewapụta arụmọrụ ihe na ịdị ọcha Peptide
Nke a bụ ajụjụ kacha ebipụta ọrụ na peptide hydrogels glosses over: kedu ka ị ga-esi mara na ihe gị na-arụ ọrụ, ma ọ bụghị naanị na peptide dị ọcha? HPLC dị ọcha na-akọwa peptide; ọ naghị akọwa gel. A 98% Peptide dị ọcha nwere ike ịghara ịza gel, jidesie ike, ma ọ bụ hapụ ọrụ antimicrobial niile ozugbo agbakọtara.
Maka ịrụ ọrụ ihe, ị chọrọ orthogonal Peptides sịntetik nyocha ọrụ na gel ikpeazụ:
- Rheology bụ isi ule. Oscillatory njupụta, ugboro ugboro, na mkpochapụ oge na-ebuga G', G″, tan δ, ebe gelation, mpaghara viscoelastic linear, ekwe omume, na mgbake / thixotropy. Nke njirimara rheological nke peptide hydrogels bụ ọkọlọtọ izizi ịgụpụta ma netwọkụ malitere n'ezie n'ihi isi ike e zubere. Mmepụta Peptide
- Mechanical ule karịrị rheology. Mkpakọ, ntinye, DMA, na micropipette aspiration na-atụle isi ike na omume ọdịda n'ụdị dabara adaba na ngwa. Ụzọ dị mfe-nyocha isi ike nwere ike imeju oscillatory rheology na-enweghị akụrụngwa pụrụ iche.
- Ọrụ mgbochi ọrịa chọrọ MIC na MBC. Broth microdilution kwa usoro CLSI, na nlebanya mgbochi mpaghara ebe okwesịrị. Ọdịnaya Peptide anaghị ebu amụma ike mgbe peptide gbakọtara - ị ga-enyocha gel ma ọ bụ mwepụta akọwapụtara..
- Adhesion bụ ihe atụpụtara iche. Kpatụ, ịdọpụ-apụ, shiee n'apata, ma ọ bụ ule adhesion anụ ahụ na gel ikpeazụ, na-eji njikwa usoro ihe dabara adaba, gosi na adhesion bụ kpọmkwem karịa mgbasa ozi hydrophobic na-abụghị nke akọwapụtara.
Maka ntọhapụ ogbe, ụkpụrụ siri ike bụ: na-agba ọsọ HPLC / LC-MS na peptide ọ bụla; kwadebe gels n'okpuru SOP ekpochi; tụọ rheology na otutu oyiri kwa ogbe megide usoro njikwa akụkọ ihe mere eme; tinye otu orthogonal n'ibu ule na otu ule ọrụ (MIC ma ọ bụ adhesion); ma soro n'ime-batch na n'etiti-ogbe mgbanwe na chaatị njikwa site na iji njedebe nkọwapụta nke etinyere na nza nke na-arụ ọrụ nke ọma - ọ bụghị site na ịdị ọcha naanị..
Echiche na-ezighi ezi a na-enwekarị iji tụfuo
- "Ịdị ọcha dị elu bụ ezigbo hydrogel." Ịdị ọcha bụ ntinye, ọ bụghị ihe si na ya pụta. Ịdị ọcha na-ekwu na peptide bụ agbụ ziri ezi; rheology, MIC, na adhesion na-ekwu na ọ bụ ihe ziri ezi.
- "Ọtụtụ bioactivity na-aka mma mgbe niile." Motifs adhesion denser ma ọ bụ ụgwọ dị elu nwere ike imebi mgbakọ, zoo saịtị ndị nọ n'ọrụ, ma ọ bụ mbanye mkpokọta. Ọrụ ọ bụla chọrọ mpio imewe akwadoro nke ya.
- "Nkwụsi ike na ọrụ bụ nkọwa dị iche." A na-ejikọta ha na usoro na crosslink larịị. Ị nweghị ike ịmezi nkwụsi ike na-enweghị ịleleghachi nrapado na mkpughe antimicrobial - na ọzọ.
- "Ịdị elu na-emekwu ihe." Ihe egwu mkpokọta, ịgwakọta, na nhazi mbanye na-eme ka nnukwu-batch gelation dị nnọọ iche na obere-ogbe. A na-ahazi nhazi nhazi nke ogbe, echeghị.
Nzọụkwụ ọzọ maka Mmemme Hydrogel Multifunctional
Ịmepụta adhesion, ọrụ antimicrobial, na nkwụsi ike n'ime otu peptide hydrogel bụ ihe na-emegharị ahụ, multi-ebumnobi nsogbu, na ụzọ kacha ọsọ na-aga n'ihu bụ iwepụ ya n'ihe ize ndụ n'oge. Usoro nhazi ọrụ ka a kwadoro mgbakọ na ọrụ dị ka ihe nrụpụta zuru oke, họrọ mgbanwe saịtị akọwapụtara nke na-adịgide adịgide nhazi mmiri, dozie gelation ma hapụ SOP, ma jide batch ọ bụla na nkọwapụta arụ ọrụ - ọ bụghị naanị nchọta HPLC.
Mgbe usoro ahụ chọrọ ọtụtụ mgbanwe orthogonal yana ụzọ ntọlite mmụgharị, onye mmekọ pụrụ iche nwere ike mechie oghere ahụ. MOL mgbanwe na-ejikọta njikọ peptide omenala na Pọtụfoliyo nke ọtụtụ narị mgbanwe otu-arụ ọrụ, Klas 100 emeputa emeputaghi mma, na multilayered analytical QC - ụdị usoro omimi nke na-atụgharị hydrogel multifunctional site na nchịkọta ogbako ka ọ bụrụ njirimara, ihe mmeghari. Ọ bụrụ na ị na-atụle ka esi ewere peptide dị mgbagwoju anya site na milligrams gaa na gel nke nwere ike imegharị kilogram., ọ bara uru mkparịta ụka n'ịrụ ọrụ teknuzu tupu itinye aka na ụzọ njikọ.
