Reduced Size Profile of Amniotic Membrane Particles Decreases Osteoarthritis Therapeutic Efficacy

Abstract

Osteoarthritis (OA) is a widespread disease that continues to lack approved and efficacious treatments that modify disease progression. Micronized dehydrated human amnion/chorion membrane (m-dHACM) has been shown to be effective in reducing OA progression, but many of the engineering design parameters have not been explored. The objectives of this study were to characterize the particle size distributions of two m-dHACM formulations and to investigate the influence of these distributions on the in vivo therapeutic efficacy of m-dHACM. Male Lewis rats underwent medial meniscus transection (MMT) or sham surgery, and intra-articular injections of saline, m-dHACM, or reduced particle size m-dHACM (RPS m-dHACM) were administered at 24 hours postsurgery (n = 9 per treatment group). After 3 weeks, the animals were euthanized, and left legs harvested for equilibrium partitioning of an ionic contrast agent microcomputed tomography and histological analysis. m-dHACM and RPS m-dHACM particles were fluorescently tagged and particle clearance was tracked in vivo for up to 42 days postsurgery. Protein elution from both formulations was quantified in vitro. Treatment with m-HACM, but not RPS m-dHACM, reduced lesion volume in the MMT model 3 weeks postsurgery. In contrast, RPS m-dHACM increased cartilage surface roughness and osteophyte cartilage thickness and volume compared to saline treatment. There was no difference of in vivo fluorescently tagged particle clearance between the two m-dHACM sizes. RPS m-dHACM showed significantly greater protein elution in vitro over 21 days. Overall, delivery of RPS m-dHACM did result in an increase of in vivo joint degeneration and in vitro protein elution compared to m-dHACM, but did not result in differences in joint clearance in vivo. These results suggest that particle size and factor elution may be tailorable factors that are important to optimize for particulate amniotic membrane treatment to be an effective therapy for OA.

A Single Injection of Amniotic Suspension Allograft Is Safe and Effective for Treatment of Mild to Moderate Hip Osteoarthritis: A Prospective Study

“…Reece et al administered μ-dHACM injections consisting of two different particle sizes, along with saline injections as a control, to a group of rats following MMT. The authors found that standard μ-dHACM resulted in decreased cartilage degeneration; however, reduced particle size μ-dHACM resulted in increased roughness of cartilage 34 . Finally, Kimmerling et al created a chemically induced OA model in rat knees and treated with saline, triamcinolone, or ASA in 25 μL or 50 μL doses.…”

Injection of Micronized Human Amnion/Chorion Membrane Results in Increased Early Supraspinatus Muscle Regeneration in a Chronic Model of Rotator Cuff Tear

“…In other studies, where micronized dHACM was intra-articularly injected into a Lewis rat model of osteoarthritis, traces of micronized dHACM were histologically observed in the synovium for 7-21 days post injection, 51,64 and the fluorescent signal of tagged micronized dHACM was observed for up to 6 weeks. 47 There are several factors that could explain the differences in dHACM retention in these two different injury models, including the avascular nature of cartilage in the knee joint 12 (compared to highly vascularized muscle), as well as multiple transport barriers in the knee joint due to the viscosity of the synovial fluid 15 and layers of the fibrous synovium (i.e. interstitium and microvascular endothelium).…”

“…[7][8][9]25 After processing, it can be administered to a wound as a membrane graft or as an injectable suspension of cryomilled particles termed micronized dHACM, in which ~89% of particles are smaller than 500 lm 2 . 47 dHACM is an attractive therapeutic agent as it possesses many soluble factors that promote processes that contribute to tissue healing, such as angiogenesis, 24,38 stem and progenitor cell recruitment, 26 as well as synthesis of ECM components. 32 While micronized dHACM has yet to be studied extensively in the context of muscle healing, these previous findings, in addition to functional improvement and decreased degeneration in other orthopedic contexts, 31,41,64 suggest that it has the potential to increase muscle healing and regeneration through the recruitment of pro-regenerative cells, in addition to orchestrating general wound healing processes.…”

Applications of the amniotic membrane in tissue engineering and regeneration: the hundred-year challenge

“…In contrast, AMEED was reported to efficiently treat dry eyes, chemical ulcers, and diffuse limbal stem cell deficiency (LSCD) [ 147 ]. In osteoarthritis, the Amnio-M was a part of μ-dam (EpiFix®) product, which showed promising efficacy in ameliorating the arthritis symptoms [ 16 , 148 ].…”

“…In 2005, it was first applied in the form of suspension eye drops (AMEED®) for corneal ulcer treatment to overcome the invasive procedure of suturing the Amnio-M graft [ 15 ]. In other clinical trials, micronized dehydrated human amnion/chorion membrane (μ-dHACM, EpiFix®) was also shown to be effective in treating diabetic foot ulcers, plantar fasciitis, and osteoarthritis (OA) with minimal invasiveness [ 16 – 19 ]. More recently, the Amnio-M was used as an effective dermal filler for facial wrinkles to restore smooth skin appearance in an in vivo rabbit model [ 20 ].…”