Intra-articular delivery of micronized dehydrated human amnion/chorion membrane reduces degenerative changes after onset of post-traumatic osteoarthritis.

Background: Micronized dehydrated human amnion/chorion membrane (mdHACM) has reduced short term post-traumatic osteoarthritis (PTOA) progression in rats when delivered 24 h after medial meniscal transection (MMT) and is being investigated for clinical use as a disease modifying therapy. Much remains to be assessed, including its potential for longer-term therapeutic benefit and treatment effects after onset of joint degeneration. Objectives: Characterize longer-term effects of acute treatment with mdHACM and determine whether treatment administered to joints with established PTOA could slow or reverse degeneration. Hypotheses: Acute treatment effects will be sustained for 6 weeks, and delivery of mdHACM after onset of joint degeneration will attenuate structural osteoarthritic changes. Methods: Rats underwent MMT or sham surgery (left leg). mdHACM was delivered intra-articularly 24 h or 3 weeks post-surgery (n = 5-7 per group). Six weeks post-surgery, animals were euthanized and left tibiae scanned using equilibrium partitioning of an ionic contrast agent microcomputed tomography (EPIC-µCT) to structurally quantify joint degeneration. Histology was performed to examine tibial plateau cartilage. Results: Quantitative 3D µCT showed that cartilage structural metrics (thickness, X-ray attenuation, surface roughness, exposed bone area) for delayed mdHACM treatment limbs were significantly improved over saline treatment and not significantly different from shams. Subchondral bone mineral density and thickness for the delayed treatment group were significantly improved over acute treated, and subchondral bone thickness was not significantly different from sham. Marginal osteophyte degenerative changes were decreased with delayed mdHACM treatment compared to saline. Acute treatment (24 h post-surgery) did not reduce longer-term joint tissue degeneration compared to saline. Histology supported µCT findings and further revealed that while delayed treatment reduced cartilage damage, chondrocytes displayed qualitatively different morphologies and density compared to sham. Conclusion: This study provides insight into effects of intra-articular delivery timing relative to PTOA progression and the duration of therapeutic benefit of mdHACM. Results suggest that mdHACM injection into already osteoarthritic joints can improve joint health, but a single, acute mdHACM injection post-injury does not prevent long term osteoarthritis associated with meniscal instability. Further work is needed to fully characterize the durability of therapeutic benefit in stable osteoarthritic joints and the effects of repeated injections.

Cryopreserved Placental Membranes Containing Viable Cells Result in High Closure Rate of Nonhealing Upper and Lower Extremity Wounds of Non-Diabetic and Non-Venous Pathophysiology.

INTRODUCTION: Higher closure rates for chronic diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) have been reported for placental products adjunct to standard of care (SOC) vs SOC alone; however, data for other types of wounds are limited. OBJECTIVE: This study aimed to evaluate the clinical outcomes of amnion-derived and chorion-derived cryopreserved placental membranes containing viable cells (vCPM) in the treatment of nonhealing upper-extremity and lower-extremity wounds of nondiabetic and nonvenous pathophysiology. The authors hypothesized that treatment with vCPM adjunct to SOC would result in positive clinical outcomes for these wounds. MATERIALS AND METHODS: Data for all patients consecutively treated between January 2016 and May 2019 with vCPM adjunct to SOC were retrospectively collected and analyzed through chart review at a single center. Patients with wounds of diabetic and venous pathophysiology and patients receiving other skin substitutes during the course of vCPM treatment were excluded from the study. Outcomes included wound closure, time to closure, number of applications, and vCPM-related adverse events (AEs). RESULTS: Ninety-two patients with 104 wounds received vCPM applications adjunct to SOC. The median wound size was 3.15 cm2 (mean, 12.7 cm2) with a median duration of 1.5 months (mean, 3.9 months). Eighty-seven of the 104 wounds (83.7%) achieved complete wound closure in a median time of 41 days and 3 applications of vCPM. There were no differences in closure rates between upper-extremity and lower-extremity wounds, nor between the amnion and chorion products. There were no vCPM-related adverse events. CONCLUSIONS: This study provides valuable information to physicians, hospitals, and payers as it pertains to medically necessary and appropriate patient treatment.

Management of a complex scalp defect with cryopreserved placental membrane containing viable cells resulted in rapid wound closure.

Reconstructive methods are most commonly used to treat scalp defects. However, patients with complex defects are often not good candidates for surgical procedures due to the severity of the wound, advanced patient age, and multiple comorbidities. In these instances, alternative nonsurgical advanced therapies should be considered.

The influence of scaffold microstructure on chondrogenic differentiation of mesenchymal stem cells.

Different forms of biomaterials, including microspheres, sponges, hydrogels and nanofibres have been broadly used in cartilage regeneration; however, effects of internal structures of biomaterials on chondrogenesis of mesenchymal stem cells (MSCs) remain largely unexplored. Here we investigated the effect of physical microenvironments of sponges and hydrogels on chondrogenic differentiation of MSCs. MSCs, cultured in these two scaffold systems, were induced with TGF-ß3 in chondrogeneic differentiation medium and the chondrogenic differentiation was evaluated and compared after three weeks. MSCs in the sponges clustered with spindle morphologies, while they distributed homogenously with round morphologies in the hydrogel. The MSCs proliferated faster in the sponge compared to that in the hydrogel. Significantly higher glycosaminoglycan and collagen II were found in the sponges but not in the hydrogels. The different tissue formation ability of MSCs in these two systems could be attributed to the different metabolic requirements and the cellular events prerequisite in the chondrogenic process of MSCs. It is reasonable to conclude that sponges with relatively active microenvironments that facilitate cell-cell contacts and cell-matrix interaction are optimal for early stage of chondrogeneic differentiation.

Intra-articular injection of micronized dehydrated human amnion/chorion membrane attenuates osteoarthritis development.

INTRODUCTION: Micronized dehydrated human amnion/chorion membrane (µ-dHACM) is derived from donated human placentae and has anti-inflammatory, low immunogenic and anti-fibrotic properties. The objective of this study was to quantitatively assess the efficacy of µ-dHACM as a disease modifying intervention in a rat model of osteoarthritis (OA). It was hypothesized that intra-articular injection of µ-dHACM would attenuate OA progression. METHODS: Lewis rats underwent medial meniscal transection (MMT) surgery to induce OA. Twenty four hours post-surgery, µ-dHACM or saline was injected intra-articularly into the rat joint. Naïve rats also received µ-dHACM injections. Microstructural changes in the tibial articular cartilage were assessed using equilibrium partitioning of an ionic contrast agent (EPIC-µCT) at 21 days post-surgery. The joint was also evaluated histologically and synovial fluid was analyzed for inflammatory markers at 3 and 21 days post-surgery. RESULTS: There was no measured baseline effect of µ-dHACM on cartilage in naïve animals. Histological staining of treated joints showed presence of µ-dHACM in the synovium along with local hypercellularity at 3 and 21 days post-surgery. In MMT animals, development of cartilage lesions at 21 days was prevented and number of partial erosions was significantly reduced by treatment with µ-dHACM. EPIC-µCT analysis quantitatively showed that µ-dHACM reduced proteoglycan loss in MMT animals. CONCLUSIONS: µ-dHACM is rapidly sequestered in the synovial membrane following intra-articular injection and attenuates cartilage degradation in a rat OA model. These data suggest that intra-articular delivery of µ-dHACM may have a therapeutic effect on OA development.

Cells behave distinctly within sponges and hydrogels due to differences of internal structure.

Different forms of biomaterials, including microspheres, sponges, hydrogels, and nanofibers, have been broadly used in cartilage regeneration; however, effects of internal structures of the biomaterials on cells and chondrogenesis remain largely unexplored. We hypothesized that different internal structures of sponges and hydrogels led to phenotypic disparity of the cells and may lead to disparate chondrogenesis. In the current study, the chondrocytes in sponges and hydrogels of chitosan were compared with regard to cell distribution, morphology, gene expression, and production of extracellular matrix. The chondrocytes clustered or attached to the materials with spindle morphologies in the sponges, while they distributed evenly with spherical morphologies in the hydrogels. The chondrocytes proliferated faster with elevated gene expression of collagen type I and down-regulated gene expression of aggracan in sponges, when compared with those in the hydrogels. However, there was no significant difference of the expression of collagen type II between these two scaffolds. Excretion of both glycosaminoglycan (GAG) and collagen type II increased with time in vitro, but there was no significant difference between the sponges and the hydrogels. There was no significant difference in secretion of GAG and collagen type II in the two scaffolds, while the levels of collagen type I and collagen type X were much higher in sponges compared with those in hydrogels during an in vivo study. Though the chondrocytes displayed different phenotypes in the sponges and hydrogels, they led to comparable chondrogenesis. An optimized design of the biomaterials could further improve chondrogenesis through enhancing functionalities of the chondrocytes.