The spiny mouse (Acomys species) has emerged as an exciting research organism due to its remarkable ability to undergo scarless regeneration of skin wounds and ear punches. Excitingly, Acomys species demonstrate scar-free healing in a wide-range of tissues beyond the skin. In this perspective article, we discuss published findings from a variety of tissues to highlight how this emerging research organism could shed light on numerous clinically relevant human diseases. We also discuss the challenges of working with this emerging research organism and suggest strategies for future Acomys-inspired research.

Neuroinflammation has long been associated with the performance decline of intracortical microelectrodes (IMEs). Consequently, several strategies, including the use of anti-inflammatories, have been employed to mitigate the inflammation surrounding IMEs. However, these strategies have had limited success towards achieving a chronically viable cortical neural interface, questioning the efficacy of anti-inflammatory approach. Herein, we conducted a systematic study in rats implanted with functional devices by modulating inflammation via systemic injection of lipopolysaccharide (LPS), dexamethasone (DEX), a combination of both, or none to assess the degree of inflammation on device functionality. We hypothesized that implanted rats treated with LPS will have a negative impact, and rats treated with DEX will have a positive impact on functionality IMEs and histological outcome. Contrary to our hypothesis, we did not observe adverse effects in recording metrics among different groups with LPS and/or DEX treatment despite alterations in initial pro-inflammatory markers. We also did not observe any functional benefit of anti-inflammatory treatment. Regardless of the treatment conditions, the recording quality degraded at chronic time points. In end-point histology, implanted rats that received LPS had significantly lower NeuN density and higher levels of CD68 surrounding the implant site, indicative of the pro-inflammatory effect of LPS, which, however, contradicted with the recorded results. Collectively, our results suggest that acute inflammatory events may not be the key driver for functional degradation of IMEs. Future intervention strategies geared towards improving the functional longevity of intracortical devices may benefit using multi-modal approaches rather than a single approach, such as controlling the initial inflammatory response.

Osteoarthritis (OA) often presents with comorbidities such as hypertension, potentially accelerating OA pathogenesis. We hypothesized that hypertension would exacerbate joint-level pathogenesis and OA-related symptoms in a sex-dependent manner. Male and female Spontaneously Hypertensive rats (hypertensive) and Sprague Dawley rats (normotensive) underwent either medial collateral ligament and medial meniscus transection (OA) or skin incision (sham) in the right knee (N ​= ​80; n ​= ​10/group/sex). Symptoms were measured monthly (gait) and bi-weekly (tactile sensitivity) for 8 weeks. Endpoint histology assessed joint-level damage, neurovascular changes, and cytokine levels in synovial fluid. At endpoint, hypertensive-OA rats had thinner cartilage across the medial tibial plateau than normotensive-OA rats (non-overlapping 95 ​% CI), regardless of sex. While not observed in males, hypertensive-OA females developed larger osteophytes (Q1–Q3 ​= ​0.049–0.124 ​mm²) than normotensive-OA females (Q1–Q3 ​= ​0.026–0.047 ​mm², p ​= ​0.02) and ranked higher for CD31⁺ vasculature in the subchondral bone plate (Q1–Q3 ​= ​18.2–21.5) than normotensive-OA females (Q1–Q3 ​= ​1; p ​= ​0.01). Hypertensive-OA females developed a limping gait, shifting stance times from their OA to non-OA limb (stance time imbalance ​= ​1.20 ​± ​1.15 ​%, p ​= ​0.04), offloaded their injured limb quicker (temporal symmetry ​= ​52.5 ​± ​1.4 ​%, p ​< ​0.001), and reduced stride lengths (weeks 4 and 8; hypertensive-OA ​< ​normotensive-OA, p ​< ​0.001). These gait changes were not observed in normotensive-OA females or males, nor in hypertensive-OA males. Hypertension worsened OA pathogenesis at the joint level, more substantially affecting joint remodeling and gait compensations in females. Our results encourage further investigation into the pathophysiologic drivers linking hypertension and OA, particularly vascular changes and sex differences.

Spiny mice ( Acomys ) can regenerate after injury with minimal fibrosis. Whether Acomys retains the fibrosis-free feature in response to implanted devices is unknown, so we implanted polydimethylsiloxane (PDMS) subcutaneously in Acomys and Mus , a non-regenerative counterpart. In Acomys , we found reduced myeloid cell infiltration, fibroblast activation, and collagen deposition around the PDMS implant. These results suggest that Acomys can regulate FBR and may hold the key to improving implant lifetime and functionality.