Table 5.
Histological Outcomes for Hydrogels Evaluated in Situ for AF Repair
| Hydrogel composition | Abbreviation | Test method of application (Species) | Experimental methods | Outcome | Refs |
|---|---|---|---|---|---|
| genipin-cross-linked fibrin | FibGen | ex vivo (bovine and ovine) | IHC | Ki67 expression did not change with a change in fibrin or genipin concentration | 62–73 |
| tinctorial staining | COL1 expression increased with a decrease in both fibrin and genipin concentration | ||||
| hydrogel was retained within defect site after mechanical loading | |||||
| in vivo (ovine) | tinctorial staining | partial degradation and cell infiltration occurs by 8 weeks and complete resorption occurs by 16 weeks | 73 | ||
| riboflavin-cross-linked collagen | RF-collagen | ex vivo (rat and ovine) | tinctorial staining | hydrogel treatment decreased NP height loss and promoted reorganization of lamellar layers | 74–77 |
| SHG | repair with collagen AF patch decreased buckling and inversion of AF lamellae | ||||
| collagen gel demonstrated significant binding with AF tissue after ChABC treatment | |||||
| in vivo (rat and ovine) | tinctorial staining | partial adherence of hydrogel to AF tissue and some biomaterial degradation observed at 2- and 5-weeks in a rat-tail model | 77–82 | ||
| SHG | repair leads to centrally retained NP tissue and formation of fibrous capsule at outer AF after 5 weeks in a rat-tail model | ||||
| acellular and MSC-laden repairs led to hypointense and hyperintense staining, respectively, at the outer AF 6-weeks postop in a sheep model | |||||
| hydrogel treatment led to increased aligned collagen in the direction of lamellar bundles in a sheep model | |||||
| Rose Bengal-cross-linked collagen | RB-collagen | ex vivo (rabbit) | IHC | injection portal was evidence 1-month postop | 83 |
| tinctorial staining | no osteophyte formation in repaired IVDs | ||||
| in vivo (rabbit) | a | a | |||
| poly(ethylene glycol)–poly(trimethylenecarbonate)–hexamethylene diisocyanate | PEG400-TMC3-HDI | ex vivo (bovine and caprine) | tinctorial staining | mechanical failure predominantly occurred at the interface between hydrogel and AF | 84,85 |
| albumin/glutaraldehyde | BioGlue | ex vivo (bovine) | a | a | 69 |
| n-butyl cyanoacrylate (n-BCA) and octyl cyanoacrylate (OCA) | cyanoacrylate/LiquiBand | ex vivo (porcine) | a | a | 86 |
| in vivo (porcine) | IHC | H&E and Picrosirius Red staining indicated signs of inflammatory reaction and fibrous scar tissue | |||
| tinctorial staining | |||||
| αSMA IHC indicated blood vessel ingrowth after repair | |||||
| citric acid-l-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide type I collagen | CA-EDC/NHScollagen | in vivo (rat) | tinctorial staining | repaired IVDs demonstrated a CA-dependent decrease in histological grading score compared to untreated IVD controls | 87 |
| H&E and Saf-O staining indicated a gel-like material was able to bridge the AF together and close the needle track | |||||
| 1-(3dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride-cross-linkedgelatin/poly(γ-glutamic acid) | EDC-gelatin-γPGA | ex vivo (bovine) | a | a | 88 |
| fibrin | fibrin | ex vivo (bovine and porcine) | tinctorial staining | histopathological scoring was not different between injured and repaired IVDs with and without CCL5 | 89,90 |
| in vivo (porcine and ovine) | repaired IVDs show improvement in AF architecture compared to injured controls and retention of NP tissue up to 12 weeks postop | ||||
| preservation of NP volume over 12 weeks | |||||
| poly(lactic-co-glycolic acid)/fibrin | PLGA/fibrin | in vivo (rat) | IHC | significant biomaterial resorption at 6 months postop with clusters of new repair tissue around remaining hydrogel | 91 |
| tinctorial staining | PGP 9.5 IHC indicated that nerve tissue extended into the inner AF region, with proximity to blood vessels and found in the generated repair tissue in the hydrogel treatment group | ||||
| Saf-O staining indicated significant decrease in proteoglycan content within the repair site | |||||
| poly(ethylene glycol) diacrylate + chondroitin sulfate or hyaluronic acid methacrylate aldehyde | PEGDA/fibrin + CSMA or HAMA aldehyde | ex vivo (bovine) | tinctorial staining | Picrosirius Red/Alcian Blue staining indicated that AF tissue and injectable hydrogel are adsorbed via GAG-mediated covalent bonds with contiguous boundaries | 92 |
| poly(lactic-co-glycolic acid) | PLGA | in vivo (rabbit) | tinctorial staining | immature repair tissue observed at 6 months postop | 93 |
| significant biomaterial degradation after 6 months | |||||
| alginate/collagen | alginate/collagen | ex vivo (bovine) | tinctorial staining | TGF-β3 incorporation enhanced collagen elaboration | 94 |
| alginate | alginate | ex vivo (bovine) | IHC | significant collagen and proteoglycan content deposited after treatment with AF cell-laden hydrogels | 95 |
| tinctorial staining | |||||
| hyaluronic acid | HA | ex vivo (bovine) | IHC | hydrogel treatment decreases IFIT3, IGFBP3 and Casp3 expression | 96 |
| hydrogel treatment increases ACAN and COL1 expression | |||||
| in vivo (rat) | IHC | hydrogel treatment decreases IGFBP3 and Casp3 expression | 97 | ||
| hydrogel treatment decreases WGA, SNA-I, MAA, CON-A binding | |||||
| hydrogel treatment increases PNA binding | |||||
| hydrogel treatment increases ACAN and HAPLN1 expression | |||||
| hyaluronic acid/albumin | HA/albumin | in vivo (ovine) | IHC | NP and AF similarity observed between repaired and intact PVDs | 98 |
| tinctorial staining | ACAN, COL1, and COL2 IHC showed maintenance of phenotype after repair | ||||
| ultrapurified alginate | UPAL | ex vivo (human and ovine) | a | a | 99 |
| in vivo (rabbit and ovine) | IHC | repaired IVDs underwent less degeneration than discectomy group 4-, 12-, and 24-weeks postop | |||
| tinctorial staining | COL2 IHC was not different between repaired and intact ovine IVDs | ||||
| cellulose nanofiber-reinforced chitosan | CNF/CHI | ex vivo (porcine) | a | a | 100 |
a
Not applicable.