Comparison of polymer scaffolds in rat spinal cord: A step toward quantitative assessment of combinatorial approaches to spinal cord repair

Abstract

The transected rat thoracic (T9/10) spinal cord model is a platform for quantitatively compa0ring biodegradable polymer scaffolds. Schwann cell-loaded scaffolds constructed from poly (lactic co-glycolic acid) (PLGA), poly(ε-caprolactone fumarate) (PCLF), oligo(polyethylene glycol) fumarate (OPF) hydrogel or positively charged OPF (OPF+) hydrogel were implanted into the model. We demonstrated that the mechanical properties (3-point bending and stiffness) of OPF and OPF+ hydrogels closely resembled rat spinal cord. After one month, tissues were harvested and analyzed by morphometry of neurofilament-stained sections at rostral, midlevel, and caudal scaffold. All polymers supported axonal growth. Significantly higher numbers of axons were found in PCLF (P < 0.01) and OPF+ (P < 0.05) groups, compared to that of the PLGA group. OPF+ polymers showed more centrally distributed axonal regeneration within the channels while other polymers (PLGA, PCLF and OPF) tended to show more evenly dispersed axons within the channels. The centralized distribution was associated with significantly more axons regenerating (P < 0.05). Volume of scar and cyst rostral and caudal to the implanted scaffold was measured and compared. There were significantly smaller cyst volumes in PLGA compared to PCLF groups. The model provides a quantitative basis for assessing individual and combined tissue engineering strategies.

An in vitro spinal cord injury model to screen neuroregenerative materials

“…Following lesion (injury) induction, introduction of synthetic scaffolds into injury areas usually requires re-anesthetization, with the second procedure involving similar risks to injury induction. In vivo models necessitate the use of analgesia and rigorous post-operative monitoring of animals, which must be housed individually [8]. The requirements for specialist staff and infrastructure in particular, place major financial constraints on such work [9,10].…”

The Application of Stem Cell Based Tissue Engineering in Spinal Cord Injury Repair.

“…These properties make it broadly used in bone [58], osteochondral [59], musculotendinous [60], cardiovascular [61] and neural tissue engineering [62,63]. OPF could serve as spinal cord regeneration matrix mainly due to its compressive and flexural modulus which is similar to that of rat spinal cord [64]. When OPF mixed with PLGA at (50:50) ratio, the scaffold was designed to deliver dibutyryl cyclic adenosine monophosphate (dbcAMP) in order to enhance the neurite outgrowth.…”

Positively Charged Oligo[Poly(Ethylene Glycol) Fumarate] Scaffold Implantation Results in a Permissive Lesion Environment after Spinal Cord Injury in Rat

“…35,42,44,45,[57][58][59][60][61] The characteristics of the 20% charged OPF+ hydrogel have been previously described as having a zeta potential of 3.7 -1.1 mV, conductivity of 0.15 -0.02 mS cm -1 , pH of 4.09-0.08, and sol fraction of 3.78% -1.87% in deionized water. 62 The compression and flexural moduli of scaffolds made from OPF+ (0.13 -0.03 MPa and 1.87 -1.03 MPa, respectively) have also been previously determined not to be significantly different from those of rat spinal cord tissue (0.19 -0.09 MPa and 0.74 -0.14 MPa, respectively).…”

“…36,40 We have also compared the mechanical properties and regeneration supporting potential of various polymers, including poly(lactic-co-glycolic acid) (PLGA), poly(caprolactone fumarate) (PCLF), a neutral oligo[(polyethylene glycol) fumarate] (OPF) hydrogel, and a positively charged oligo [(polyethylene glycol) fumarate] (OPF+) hydrogel and determined that scaffolds fabricated from OPF+ support the most axon regeneration and have similar compression and flexural moduli to rat spinal cord. 45 OPF+ has also been shown to support neurite outgrowth and myelination of dorsal root ganglia when cocultured with Schwann cells in vitro. 35 However, even the amount of axonal regeneration achieved with OPF+ scaffolds loaded with Schwann cells is not sufficient for inducing any significant recovery of hind limb function after complete spinal cord transection.…”

“…35 However, even the amount of axonal regeneration achieved with OPF+ scaffolds loaded with Schwann cells is not sufficient for inducing any significant recovery of hind limb function after complete spinal cord transection. 45 Thus, further optimization of these Schwann cell-loaded OPF+ scaffolds is necessary; requiring an analysis of the CNS tissue response to implantation in the injured spinal cord, which has not been a previous focus of study.…”