Biomaterial-based interventions for neuronal regeneration and functional recovery in rodent model of spinal cord injury: A systematic review

Abstract

Context: There is considerable interest in translating laboratory advances in neuronal regeneration following spinal cord injury (SCI). A multimodality approach has been advocated for successful functional neuronal regeneration. With this goal in mind several biomaterials have been employed as neuronal bridges either to support cellular transplants, to release neurotrophic factors, or to do both. A systematic review of this literature is lacking. Such a review may provide insight to strategies with a high potential for further investigation and potential clinical application. Objective: To systematically review the design strategies and outcomes after biomaterial-based multimodal interventions for neuronal regeneration in rodent SCI model. To analyse functional outcomes after implantation of biomaterial-based multimodal interventions and to identify predictors of functional outcomes. Methods: A broad PubMed, CINHAL, and a manual search of relevant literature databases yielded data from 24 publications; 14 of these articles included functional outcome information. Studies reporting behavioral data in rat model of SCI and employing biodegradable polymer-based multimodal intervention were included. For behavioral recovery, studies using severe injury models (transection or severe clip compression (>16.9 g) or contusion (50 g/cm)) were categorized separately from those investigating partial injury models (hemisection or moderate-to-severe clip compression or contusion). Results: The cumulative mean improvements in Basso, Beattie, and Bresnahan scores after biomaterial-based interventions are 5.93 (95% CI = 2.41 − 9.45) and 4.44 (95% CI = 2.65 -6.24) for transection and hemisection models, respectively. Factors associated with improved outcomes include the type of polymer used and a follow-up period greater than 6 weeks. Conclusion: The functional improvement after implantation of biopolymer-based multimodal implants is modest. The relationship with neuronal regeneration and functional outcome, the effects of inflammation at the site of injury, the prolonged survival of supporting cells, the differentiation of stem cells, the effective delivery of neurotrophic factors, and longer follow-up periods are all topics for future elucidation. Future investigations should strive to further define specific factors associated with improved functional outcomes in clinically relevant models.

Functional recovery in spinal cord injured rats using polypyrrole/iodine implants and treadmill training

“…Because others have described the functional improvement after implantation of different biopolymers to be modest (for review see [33]), one of the goal of the present work was to increase the potential beneficial effects that our research group obtained before using implantation of PPy/I [18,19]. Thus, this therapeutic strategy was used in combination with locomotor training on a treadmill.…”

“…Although different injectable biomaterials have been used previously in rats as implants after a TSCI such as collagen, fibrin, fibronectin and poly (lactic acid)-polyethylene glycol-poly(lactic acid), those implants enhance and support the oriented growth of axons but with a modest functional recovery [33][34][35]. Cigognini et al [36] reported a self-assembling of the peptide RADA 16-I functionalized with a bone marrow homing motif (BMHP1) and optimized via the insertion of a 4-glycine-spacer (RADA16-4G-BMHP1) that was implanted immediately after a TSCI by contusion in rats.…”

“…A number of them displayed good integration with the host and were able to support axonal ingrowth in association with the infiltration of Schwann cells and deposit of laminin [37]; however, the collagen implant resulted in uneven axonal growth because these implants contained a dense inclusion that the axons were not able to penetrate, whereas the animals implanted with FN had large cavities at the interface between the implant and host, and few surviving neurons in the intact spinal cord adjoining the implant site. Only the animals implanted with FB/FN showed a robust growth of axons [33]. Among the main characteristics of these materials is their rapid transformation from a liquid to a gel after being injected into the injured spinal cord and the formation of a scaffold thereafter; however, even if the implants show good integration into the nervous tissue and they promote axonal regeneration, one must consider that they are biodegradable materials.…”

Application of helium ion microscopy to nanostructured polymer materials

“…Many biopolymers exhibit fascinating properties such as biomolecular recognition and selfassembly creating the possibility for new biodegradable, biocompatible, and bioinspired materials in the near future. The biomaterials will be used in countless applications including biosensor devices, targeted assembly and drug delivery, tissue engineering and regeneration, implant materials, smart stimuli responsive surfaces, artificial neuron networks and adaptive systems, bioelectronics, and bio-MEMS [4][5][6][7].…”

Potential variables affecting the quality of animal studies regarding pathophysiology of traumatic spinal cord injuries

“…6 Recently, systematic reviews in the animal experimentation field have attracted great attention, [7][8][9] although there are not adequate guidelines for assessing the quality of experimental animal studies. In this regard, a few groups of researchers focused on the development of publication guidelines in order to improve the reporting transparency, which makes future systematic reviews more feasible and allows the researchers to replicate previously published papers.…”