Collagen-glycosaminoglycan Matrix Research Articles

Acellular collagen-glycosaminoglycan matrix promotes functional recovery in a rat model of volumetric muscle loss.

Aim: Volumetric muscle loss (VML) is a composite loss of skeletal muscle, which heals with fibrosis, minimal muscle regeneration, and incomplete functional recovery. This study investigated whether collagen-glycosaminoglycan scaffolds (CGS) improve functional recovery following VML. Methods: 15Sprague-Dawley rats underwent either sham injury or bilateral tibialis anterior (TA) VML injury, with or without CGS implantation. Results: In rats with VML injuries treated with CGS, the TA exhibited greater in vivo tetanic forces and in situ twitch and tetanic dorsiflexion forces compared with those in the non-CGS group at 4- and 6-weeks following injury, respectively. Histologically, the VML with CGS group demonstrated reduced fibrosis and increased muscle regeneration. Conclusion: Taken together, CGS implantation has potential augment muscle recovery following VML.

An Engineered Dermal Substitute with Mesenchymal Stem Cells Enhances Cutaneous Wound Healing.

The treatment of refractory cutaneous wounds remains to be a clinical challenge. There is growing evidence to show that mesenchymal stem cells (MSCs) have great potential in promoting wound healing. However, the therapeutic effects of MSCs are greatly dampened by their poor survival and engraftment in the wounds. To address this limitation, in this study, MSCs were grown into a collagen-glycosaminoglycan (C-GAG) matrix to form a dermis-like tissue sheet, named engineered dermal substitute (EDS). When seeded on C-GAG matrix, MSCs adhered rapidly, migrated into the pores, and proliferated readily. When applied onto excisional wounds in healthy and diabetic mice, the EDS survived well, and accelerated wound closure, compared with C-GAG matrix alone or MSCs in collagen hydrogel. Histological analysis revealed that EDS prolonged the retention of MSCs in the wounds, associated with increased macrophage infiltration and enhanced angiogenesis. RNA-Seq analysis of EDS-treated wounds uncovered the expression of abundant human chemokines and proangiogenic factors and their corresponding murine receptors, suggesting a mechanism of ligand/receptor-mediated signals in wound healing. Thus, our results indicate that EDS prolongs the survival and retention of MSCs in the wounds and enhances wound healing.

The Use of Collagen-Glycosaminoglycan Biodegradable Matrix (Integra®) in the Management of Neck Postburn Hypertrophic Scars and Contractures

Glycosaminoglycan (GAG) is a chain-like disaccharide that is linked to a polypeptide core to connect two collagen fibrils/fibers and provide the intermolecular force in a Collagen-GAG matrix which can be a valuable treatment of post-burn contractures and hypertrophic scars, which remain a challenge to reconstructive surgery. The face and neck contractures are the most difficult sites to treat. This article is meant to discuss our clinical experience in using collagen-glycosaminoglycan biodegradable matrix (Integra® Integra Lifesciences Corporation, Plainsboro, NJ, USA) to reconstruct defects created by excision of contracted areas from the neck and lower face areas. Between 2009 and 2011, we had 11 patients that underwent Integra reconstructive procedures. The mean follow-up period was 18 months. For all the patients, the intake of the Integra dermal regeneration template was 100%, even if one patient developed a minor infection treated with appropriate antibiotics. The patients are very satisfied with the result. A minor problem was a small difference in skin color, but this inconvenience was compensated by good skin elasticity.

Neuroprotective Effects of Collagen-Glycosaminoglycan Matrix Implantation following Surgical Brain Injury.

Background Neurological deficits following neurosurgical procedures are inevitable; however, there are still no effective clinical treatments. Earlier reports revealed that collagen-glycosaminoglycan (CG) matrix implantation promotes angiogenesis, neurogenesis, and functional recovery following surgical brain injury (SBI). The present study was conducted to further examine the potential neuroprotective effects of collagen-glycosaminoglycan (CG) matrix implantation following neurosurgery. Methods CG implantation was performed in the lesion cavity created by surgical trauma. The Sprague-Dawley rat model of SBI was used as established in the previous study by the author. The rats were divided into three groups as follows: (1) sham (SHAM), (2) surgery-induced lesion cavity (L), and (3) CG matrix implantation following surgery-induced lesion cavity (L+CG). Proinflammatory (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells)) and anti-inflammatory (IL-10 and granulocyte-macrophage colony-stimulating factor (GMCSF)) cytokine expression was evaluated by enzyme-linked immunosorbent assays. Microglial activation was evaluated by immunohistochemistry, and the neuroprotective effect of CG matrix implantation was evaluated by an immunohistochemical study of microglia ED-1 and IBA-1 (activated microglia) and myeloperoxidase (MPO) and by the analysis of IL-6, IL-10, TNF-α, NF-κB, and GMCSF cytokine levels. Apoptosis was also assessed using a TUNEL assay. Results The results showed that CG matrix implantation following surgically induced lesions significantly decreased the density of ED-1, IBA-1, and MPO (activated microglia). The tissue concentration of proinflammatory cytokines, such as TNF-α, IL-6, and NF-κB was significantly decreased. Conversely, the anti-inflammatory cytokines GMCSF and IL-10 were significantly increased. Conclusions Implantation of the CG matrix following SBI has neuroprotective effects, including the suppression of microglial activation and the production of inflammatory-related cytokines.

A case of burn scar carcinoma on the wrist reconstructed with a collagen-glycosaminoglycan matrix

A case of burn scar carcinoma on the wrist reconstructed with a collagen-glycosaminoglycan matrix

The healing effect of the collagen-glycosaminoglycan copolymer on corneal thinning

BackgroundTo study the healing processes of partial thickness wounds in the adult rabbit cornea after grafting a porous collagen-glycosaminoglycan copolymer matrix (CG).MethodsIn this study, the regeneration of surgically-induced rabbit corneal defect implanted with CG was investigated. The corneal partial thickness wound was created by 7.5 mm trephine. The wound was implanted with CG. Effects on wound healing was analyzed using clinical data on epithelial migration and corneal thickness, and histological data on collagen and alpha smooth muscle actin distribution.ResultsCompared with control group, CG induced a relatively severe inflammatory reaction in grafted cornea until the CG matrix was completely degraded. The new vessel ingrowth and stromal regeneration maintained the corneal thickness. The grafted cornea was significantly thicker (P < 0.001) than the control group. On day 90, the corneal opacity score of the control group was one and the grafted cornea was two.ConclusionCG copolymer matrix can successfully repair the damaged corneal stroma by injury, and regain its thickness. However, CG matrix induced inflammatory healing process thus causing mild corneal haziness and neovascularization.

Enhancement of matrix metalloproteinases 2 and 9 accompanied with neurogenesis following collagen glycosaminoglycan matrix implantation after surgical brain injury.

Surgical brain injury may result in irreversible neurological deficits. Our previous report showed that partial regeneration of a traumatic brain lesion is achieved by implantation of collagen glycosaminoglycan (CGM). Matrix metalloproteinases (MMPs) may play an important role in neurogenesis but there is currently a lack of studies displaying the relationship between the stimulation of MMPs and neurogenesis after collagen glycosaminoglycan implantation following surgical brain trauma. The present study was carried out to further examine the expression of MMP2 and MMP9 after implantation of collagen glycosaminoglycan (CGM) following surgical brain trauma. Using the animal model of surgically induced brain lesion, we implanted CGM into the surgical trauma. Rats were thus divided into three groups: (1) sham operation group: craniotomy only; (2) lesion (L) group: craniotomy + surgical trauma lesion; (3) lesion + CGM (L + CGM) group: CGM implanted following craniotomy and surgical trauma lesion. Cells positive for SOX2 (marker of proliferating neural progenitor cells) and matrix metalloproteinases (MMP2 and MMP9) in the lesion boundary zone were assayed and analyzed by immunofluorescence and ELISA commercial kits, respectively. Our results demonstrated that following implantation of CGM after surgical brain trauma, significant increases in MMP2+/SOX2+ cells and MMP9+/SOX2+ cells were seen within the lesion boundary zone in the L + CGM group. Tissue protein concentrations of MMP2 and MMP9 also increased after CGM scaffold implantation. These findings suggest that implantation of a CGM scaffold alone after surgical brain trauma can enhance the expression of MMP2 and MMP9 accompanied by neurogenesis.

Innovations in Glaucoma Surgery: Improving the Results.

Glaucoma still represents the most frequent cause of irreversible blindness worldwide. The technological advances lead to innovative surgeries, which are rapidly introduced in clinical practice. New devices to lower intraocular pressure without opening the eye wall, bypassing the trabecular meshwork, or shunting the aqueous humor to the suprachoroidal space have been approved undergoing clinical assessment within clinical trials. Currently, other devices under evaluation are showing promising results. Although these methods will increase the options available for glaucoma surgeons, it is unclear if they could replace the present standard surgeries, such as trabeculectomy, deep sclerectomy, and glaucoma drainage devices. Moreover, the standard procedures are continuously modified in different ways to become safer and more effective. In this issue L. Choritz et al. investigate whether increased concentrations of endothelin-1 in the aqueous humor samples of glaucoma patients influenced wound healing and bleb fibrosis after standard trabeculectomy with mitomycin C. Endothelin-1 is a potent vasoconstrictor produced in the eye by the ciliary epithelium and to be released into the aqueous humor. It has been implicated in the pathophysiology of glaucoma. Endothelin-1 is believed to be involved in the regulation of intraocular pressure (IOP) via effects on the contractility of ciliary muscle and trabecular meshwork. W. Niu et al. evaluated the efficacy and safety of three different biodegradable terpolymers after trabeculectomy in rabbit eyes compared with Ologen™. The use of these implants aims to reduce the use of mitomycin C as an antiscarring agent. The first implant used was a porous collagen-glycosaminoglycan matrix, which prevents the adhesion of the conjunctiva and sclera and the collapse of the subconjunctival space after trabeculectomy, leading to collagen deposition and microcyst formation after penetrating antiglaucomatous surgery. Despite the increasing use of antifibrotic agents to modulate the wound healing response, bleb failure remains a common complication of glaucoma filtration surgery. In the paper by W. Liu et al. the needle revision and subconjunctival mitomycin C injection were compared with needling and subconjunctival 5-Fluorouracil injection for early dysfunctional filtration blebs after trabeculectomies. Neovascular glaucoma is one of the most recalcitrant glaucoma types to treatment and has one of the worst outcomes compared to other types of glaucoma. Neovascular glaucoma often needs surgical treatment because medical treatment fails to adequately control intraocular pressure. In a retrospective study, H. Yan investigated the long term surgical outcomes, treating neovascular glaucoma complicated by vitreous haemorrhage with 23-gauge vitrectomy combined with phacoemulsification, panretinal laser photocoagulation, and trabeculectomy without using anti-VEGF agents. C. Cagini et al. explored the role of canaloplasty in the surgical management of glaucoma with an extensive review. Canaloplasty is a nonpenetrating blebless surgical technique for open-angle glaucoma, similar to viscocanalostomy, in which a flexible microcatheter is inserted within Schlemm's canal for the entire 360 degrees. The results of this ab externo technique are really encouraging. S. A. Gandolfi et al. compared canaloplasty with an ab interno minimally invasive glaucoma surgery, the Hydrus™ implant. Both techniques are innovative and aim to restore the natural pathway, dilating a large size of Schlemm's canal. The results of this retrospective, comparative case series were collected after 2-year follow-up. A. F. Resende et al. presented a review on the iStent. This trabecular bypass stent is another minimally invasive glaucoma surgery device that has quickly gained popularity in the last years. Randomized controlled trials are still needed to assess the role of these devices in glaucoma surgery. Finally, S. Jacob et al. presented a new surgical technique, the stab incision glaucoma surgery. Even though it looks similar to standard trabeculectomy the main advantages are the sliding of the superior conjunctiva without dissecting, the creation of a superficial corneoscleral tunnel in a single step, the punch of the internal lip of the tunnel, and finally the suture of the conjunctival incision alone. In summary, this issue includes different approaches presented by diverse authors covering several topics related to improving of standard filtering surgery and wound healing and to new surgical techniques. This publication will provide valuable information that should be helpful in clinical practice for the whole ophthalmology community, mainly for glaucoma surgeons. Michele Figus Shlomo Melamed Antonio Ferreras Giorgio Marchini Vital P. Costa

Novel use of a flowable collagen–glycosaminoglycan matrix (Integra™ Flowable Wound Matrix) combined with percutaneous cannula scar tissue release in treatment of post-burn malfunction of the hand—A preliminary 6 month follow-up

IntroductionLong-term function following severe burns to the hand may be poor secondary to scar adhesions to the underlying tendons, webspaces, and joints. In this pilot study, we report the feasibility of applying a pasty dermal matrix combined with percutaneous cannula teno- and adhesiolysis. Patients and methodsIn this 6 month follow-up pilot study, we included eight hands in five patients with hand burns undergoing minimal-invasive, percutaneous cannula adhesiolysis and injection of INTEGRA™ Flowable Wound Matrix for a pilot study of this new concept. The flowable collagen–glycosaminoglycan wound matrix (FCGWM) was applied with a buttoned 2mm cannula to induce formation of a neo-gliding plane. Post treatment follow-up was performed to assess active range of motion (AROM), grip strength, Disabilities of the Arm, Shoulder and Hand (DASH) score, Vancouver Scar Scale (VSS) and quality of life Short-Form (SF)-36 questionnaire. ResultsNo complications were detected associated with the treatment of FCGWM injection. The mean improvement (AROM) at 6 months was 30.6° for digits 2–5. The improvement in the DASH score was a mean of 9 points out of 100. The VSS improved by a mean of 2 points out of 14. DiscussionThe study demonstrates the feasibility and safety of percutaneous FCGWM for dermal augmentation after burn. Results from this pilot study show improvements in AROM for digits 2–5, functional scores from the patient's perspective (DASH) and scar quality (VSS). The flowable form of established INTEGRA™ wound matrix offers the advantage of minimal-invasive injection after scar release in the post-burned hand with a reduction in the risk of postsurgical re-scarring.

Incorporation of fibrin into a collagen–glycosaminoglycan matrix results in a scaffold with improved mechanical properties and enhanced capacity to resist cell-mediated contraction

Fibrin has many uses as a tissue engineering scaffold, however many in vivo studies have shown a reduction in function resulting from the susceptibility of fibrin to cell-mediated contraction. The overall aim of the present study was to develop and characterise a reinforced natural scaffold using fibrin, collagen and glycosaminoglycan (FCG), and to examine the cell-mediated contraction of this scaffold in comparison to fibrin gels. Through the use of an injection loading technique, a homogenous FCG scaffold was developed. Mechanical testing showed a sixfold increase in compressive modulus and a thirtyfold increase in tensile modulus of fibrin when reinforced with a collagen–glycosaminoglycan backbone structure. Human vascular smooth muscle cells (vSMCs) were successfully incorporated into the FCG scaffold and demonstrated excellent viability over 7days, while proliferation of these cells also increased significantly. VSMCs were seeded into both FCG and fibrin-only gels at the same seeding density for 7days and while FCG scaffolds did not demonstrate a reduction in size, fibrin-only gels contracted to 10% of their original diameter. The FCG scaffold, which is composed of natural biomaterials, shows potential for use in applications where dimensional stability is crucial to the functionality of the tissue. Statement of SignificanceFibrin is a versatile scaffold for tissue engineering applications, but its weak mechanical properties leave it susceptible to cell-mediated contraction, meaning the dimensions of the fibrin construct will change over time. We have reinforced fibrin with a collagen glycosaminoglycan matrix and characterised the mechanical properties and bioactivity of the reinforced fibrin (FCG). This is the first scaffold manufactured from all naturally derived materials that resists cell-mediated contraction. In fact, over 7days, the FCG scaffold fully resisted cell-mediated contraction of vascular smooth muscle cells. This FCG scaffold has many potential applications where natural scaffold materials can encourage regeneration.

Biodegradable Collagen Implants in Trabeculectomy

ABSTRACTSubconjunctival and subscleral fibrosis are the major causes of failure of filtering surgery. Antiproliferative agents have been successfully used to improve the long-term success of this surgery. Recent advancement in the field of glaucoma surgery has been the use of bioengineered, biodegradable, porous collagen-glycosaminoglycan matrix implant in the subconjunctival and/or subscleral space to modify the wound-healing process and reduce scar formation, hence improving the surgical success without the need for anti-fibrotic agents.Biodegradable, collagen implants have shown favorable results when used with deep sclerectomy. There have been variable results regarding the success of trabeculectomy when combined with these implants. These implants also decrease the dose of mitomycin C required with trabeculectomy and hence, decrease the side effect associated with these drugs.The use of the biodegradable implants in glaucoma surgery is still evolving and further studies are needed to find the appropriate surgical technique, the ideal size and site of placement and determine their long-term impact on trabeculectomy outcomes and complications.How to cite this article: Ichhpujani P, Dada T, Bhartiya S. Biodegradable Collagen Implants in Trabeculectomy. J Curr Glaucoma Pract 2015;9(1):24-27.

Cell encapsulation in a magnetically aligned collagen–GAG copolymer microenvironment

Engineered tissue microenvironments impart specialized cues that drive distinct cellular phenotypes and function. Microenvironments with defined properties, such as mechanical properties and fibril alignment, can elicit specific cellular responses that emulate those observed in vivo. Collagen- and glycosaminoglycan (GAG)-based tissue matrices have been popularized due to their biological ubiquity in a broad range of tissues and the ability to tune structure and mechanical properties through a variety of processes. Here, we investigate the combined effects of static magnetic fields, and GAG and cell encapsulation, on the structure (e.g. collagen fibril orientation) and material properties of collagen matrices. We found that magnetic fields align the collagen–GAG matrix, alter equilibrium mechanical properties and provide a method for encapsulating cells within a three-dimensional aligned matrix. Cells are encapsulated prior to polymerization, allowing for controlled cell density and eliminating the need for cell seeding. Increased relative GAG concentrations reduced the ability to magnetically align collagen fibrils, in part through a mechanism involving increased viscosity and polymerization time of the collagen–GAG solution. This work provides a functional design space for the development of pure collagen and hybrid collagen–GAG matrices in the presence of magnetic fields. Additionally, this work shows that magnetic fields are effective for the fabrication of collagen constructs with controlled fibril orientation, and can be coupled with GAG incorporation to modulate mechanical properties and the response of embedded cells.

Structure of collagen-glycosaminoglycan matrix and the influence to its integrity and stability.

Glycosaminoglycan (GAG) is a chain-like disaccharide that is linked to polypeptide core to connect two collagen fibrils/fibers and provide the intermolecular force in Collagen-GAG matrix (C-G matrix). Thus, the distribution of GAG in C-G matrix contributes to the integrity and mechanical properties of the matrix and related tissue. This paper analyzes the transverse isotropic distribution of GAG in C-G matrix. The angle of GAGs related to collagen fibrils is used as parameters to qualify the GAGs isotropic characteristic in both 3D and 2D rendering. Statistical results included that over one third of GAGs were perpendicular directed to collagen fibril with symmetrical distribution for both 3D matrix and 2D plane cross through collagen fibrils. The three factors tested in this paper: collagen radius, collagen distribution, and GAGs density, were not statistically significant for the strength of Collagen-GAG matrix in 3D rendering. However in 2D rendering, a significant factor found was the radius of collagen in matrix for the GAGs directed to orthogonal plane of Collagen-GAG matrix. Between two cross-section selected from Collagen-GAG matrix model, the plane cross through collagen fibrils was symmetrically distributed but the total percentage of perpendicular directed GAG was deducted by decreasing collagen radius. There were some symmetry features of GAGs angle distribution in selected 2D plane that passed through space between collagen fibrils, but most models showed multiple peaks in GAGs angle distribution. With less GAGs directed to perpendicular of collagen fibril, strength in collagen cross-section weakened. Collagen distribution was also a factor that influences GAGs angle distribution in 2D rendering. True hexagonal collagen packaging is reported in this paper to have less strength at collagen cross-section compared to quasi-hexagonal collagen arrangement. In this work focus is on GAGs matrix within the collagen and its relevance to anisotropy.

Aligned collagen-GAG matrix as a 3D substrate for Schwann cell migration and dendrimer-based gene delivery.

The development of artificial off-the-shelf conduits that facilitate effective nerve regeneration and recovery after repair of traumatic nerve injury gaps is of fundamental importance. Collagen-glycosaminoglycan (GAG) matrix mimicking Schwann cell (SC) basal lamina has been proposed as a suitable and biologically rational substrate for nerve regeneration. In the present study, we have focused on the permissiveness of this matrix type for SC migration and repopulation, as these events play an essential role in nerve remodeling. We have also demonstrated that SCs cultured within collagen-GAG matrix are compatible with non-viral dendrimer-based gene delivery, that may allow conditioning of matrix-embedded cells for future gene therapy applications.

Collagen-glycosaminoglycan matrix implantation promotes angiogenesis following surgical brain trauma.

Surgical brain injury (SBI) is unavoidable during many neurosurgical procedures intrinsically linked to postoperative neurological deficits. We have previously demonstrated that implantation of collagen glycosaminoglycan (CG) following surgical brain injury could significantly promote functional recovery and neurogenesis. In this study we further hypothesized that this scaffold may provide a microenvironment by promoting angiogenesis to favor neurogenesis and subsequent functional recovery. Using the rodent model of surgical brain injury as we previously established, we divided Sprague-Dawley male rats (weighting 300–350 g) into three groups: (1) sham (2) surgical injury with a lesion (L), and (3) L with CG matrix implantation (L + CG). Our results demonstrated that L + CG group showed a statistically significant increase in the density of vascular endothelial cells and blood vessels over time. In addition, tissue concentrations of angiogenic growth factors (such as VEGF, FGF2, and PDGF) significantly increased in L + CG group. These results suggest that implantation of a CG scaffold can promote vascularization accompanied by neurogenesis. This opens prospects for use of CG scaffolds in conditions such as brain injury including trauma and ischemia.

Secondary subconjunctival implantation of a biodegradable collagen-glycosaminoglycan matrix to treat ocular hypotony following trabeculectomy with mitomycin C

AimBiodegradable collagen glycosaminoglycan matrices (CGM) have been introduced to glaucoma filtration surgery in order to prevent scarring of the filtering bleb. In this retrospective case series, we describe a new...

Improved Healing of Large Segmental Defects in the Rat Femur by Reverse Dynamization in the Presence of Bone Morphogenetic Protein-2

Large segmental defects in bone do not heal well and present clinical challenges. This study investigated modulation of the mechanical environment as a means of improving bone healing in the presence of bone morphogenetic protein (BMP)-2. Although the influence of mechanical forces on the healing of fractures is well established, no previous studies, to our knowledge, have described their influence on the healing of large segmental defects. We hypothesized that bone-healing would be improved by initial, low-stiffness fixation of the defect, followed by high-stiffness fixation during the healing process. We call this reverse dynamization. A rat model of a critical-sized femoral defect was used. External fixators were constructed to provide different degrees of stiffness and, importantly, the ability to change stiffness during the healing process in vivo. Healing of the critical-sized defects was initiated by the implantation of 11 μg of recombinant human BMP (rhBMP)-2 on a collagen sponge. Groups of rats receiving BMP-2 were allowed to heal with low, medium, and high-stiffness fixators, as well as under conditions of reverse dynamization, in which the stiffness was changed from low to high at two weeks. Healing was assessed at eight weeks with use of radiographs, histological analysis, microcomputed tomography, dual x-ray absorptiometry, and mechanical testing. Under constant stiffness, the low-stiffness fixator produced the best healing after eight weeks. However, reverse dynamization provided considerable improvement, resulting in a marked acceleration of the healing process by all of the criteria of this study. The histological data suggest that this was the result of intramembranous, rather than endochondral, ossification. Reverse dynamization accelerated healing in the presence of BMP-2 in the rat femur and is worthy of further investigation as a means of improving the healing of large segmental bone defects. These data provide the basis of a novel, simple, and inexpensive way to improve the healing of critical-sized defects in long bones. Reverse dynamization may also be applicable to other circumstances in which bone-healing is problematic.

The Effect of Collagen Nerve Conduits Filled with Collagen-Glycosaminoglycan Matrix on Peripheral Motor Nerve Regeneration in a Rat Model

Bioabsorbable unfilled synthetic nerve conduits have been used in the reconstruction of small segmental nerve defects with variable results, especially in motor nerves. We hypothesized that providing a synthetic mimic of the Schwann cell basal lamina in the form of a collagen-glycosaminoglycan (GAG) matrix would improve the bridging of the nerve gap and functional motor recovery. A unilateral 10-mm sciatic nerve defect was created in eighty-eight male Lewis rats. Animals were randomly divided into four experimental groups: repair with reversed autograft, reconstruction with collagen nerve conduit (1.5-mm NeuraGen, Integra LifeSciences), reconstruction with collagen nerve conduit filled with collagen matrix, and reconstruction with collagen nerve conduit filled with collagen-GAG (chondroitin-6-sulfate) matrix. Nerve regeneration was evaluated at twelve weeks on the basis of the compound muscle action potential, maximum isometric tetanic force, and wet muscle weight of the tibialis anterior muscle, the ankle contracture angle, and nerve histomorphometry. The use of autograft resulted in significantly better motor recovery compared with the other experimental methods. Conduit filled with collagen-GAG matrix demonstrated superior results compared with empty conduit or conduit filled with collagen matrix with respect to all experimental parameters. Axon counts in the conduit filled with collagen-GAG matrix were not significantly different from those in the reversed autograft at twelve weeks after repair. The addition of the synthetic collagen basal-lamina matrix with chondroitin-6-sulfate into the lumen of an entubulation repair significantly improved bridging of the nerve gap and functional motor recovery in a rat model. Use of a nerve conduit filled with collagen-GAG matrix to bridge a motor or mixed nerve defect may result in superior functional motor recovery compared with commercially available empty collagen conduit. However, nerve autograft remains the gold standard for reconstruction of a segmental motor nerve defect.

Does Extracorporeal Shock Wave Therapy Enhance Healing of Osteochondritis Dissecans of the Rabbit Knee?: A Pilot Study

Severe osteochondritis dissecans (OCD) in children and adolescents often necessitates surgical interventions (ie, drilling, excision, or débridement). Since extracorporeal shock wave therapy (ESWT) enhances healing of long-bone nonunion fractures, we speculated ESWT would reactivate the healing process in OCD lesions. We asked whether ESWT would enhance articular cartilage quality, bone and cartilage density, and histopathology of osteochondral lesions compared to nontreated controls in an OCD rabbit model. We harvested a 4-mm-diameter plug of the weightbearing osteochondral surface on the medial femoral condyle of each knee in 20 skeletally immature (8-week-old) female rabbits. We placed a piece of acellular collagen-glycosaminoglycan matrix into the cavity and then replaced the plug. Two weeks after surgery, we sedated each rabbit and treated the right knee in a single setting with shock waves: 4000 impulses at 4Hz and 18kV. The left knee was a sham control. Ten weeks after surgery, we assessed cartilage morphology of the lesion using a modified Outerbridge Grading System, bone and cartilage density using histologic imaging, bone and cartilage morphology using the histopathology assessment system, and radiographic bone density and union and compared these parameters between ESWT-treated and control knees. Histologically, we observed more mature bone formation and better healing (1.1 versus 3.4) and density of the cartilage (60 versus 49) on the treated side. Radiographically, we noted an increase in bony density (154 versus 138) after ESWT. ESWT accelerated the healing rate and improved cartilage and subchondral bone quality in the OCD rabbit model. This therapeutic modality may be applicable in OCD treatment in the pediatric population. Future research will be necessary to determine whether it may play a role in healing of human osteochondral defects.

The application of tissue engineering in reversing mitomycin C‐induced ischemic conjunctiva

The purpose of this study is to evaluate the angiogenic potential of collagen-glycosaminoglycan (CG) matrices in mitomycin C-induced ischemic conjunctival defect, in New Zealand white rabbits. After creating a conjunctival defect at the center of ischemic conjunctiva, a CG matrix was implanted into subconjunctival space to evaluate the conjunctival reepithelialization and angiogenesis during the wound healing process. In the grafted group, the vessel count of the healed conjunctiva was substantially elevated by two fold within the initial 4 weeks and the increased vascular content originated mostly from the fornix site. The rate of conjunctival reepithelialization was not retarded in the grafted group, and the final thickness of healed conjunctiva was similar in both grafted and ungrafted groups. The histological studies revealed that the collagen matrix did not elicit pronounced inflammatory reaction and the regenerated conjunctiva showed loosely arranged collagen deposition without significant scar formation. The α SMA staining positive myofibroblasts were identified in the acute inflammatory stage and were absent, 8 weeks after implantation in both groups. The results indicated that the porous collagen scaffold was able to enhance vascularization and physiological recovery of ischemic conjunctival defect, implying a potential alternative therapy for the ischemic leaking bleb after glaucoma filtrating surgery in ophthalmic practices.