Cyclodextrin-modified poly(octamethylene citrate) polymers towards enhanced sorption properties.

Herein, we describe the synthesis of poly(1,8-octamethylene citrate) materials modified in the bulk with 2-hydroxypropyl-ß-cyclodextrin (cPOCCD), biodegradable elastomers with intrinsic sorption properties for drug delivery. The chemical structure, physicochemical properties, in vitro drug loading and release profiles of cPOCCD were investigated. Thus, cPOCCD polyesters absorb the studied drugs more effective and release them for a longer period of time than poly(1,8-octamethylene citrate) materials not containing cyclodextrins.

Targeting Heparin to Collagen within Extracellular Matrix Significantly Reduces Thrombogenicity and Improves Endothelialization of Decellularized Tissues.

Thrombosis within small-diameter vascular grafts limits the development of bioartificial, engineered vascular conduits, especially those derived from extracellular matrix (ECM). Here we describe an easy-to-implement strategy to chemically modify vascular ECM by covalently linking a collagen binding peptide (CBP) to heparin to form a heparin derivative (CBP-heparin) that selectively binds a subset of collagens. Modification of ECM with CBP-heparin leads to increased deposition of functional heparin (by ∼7.2-fold measured by glycosaminoglycan composition) and a corresponding reduction in platelet binding (>70%) and whole blood clotting (>80%) onto the ECM. Furthermore, addition of CBP-heparin to the ECM stabilizes long-term endothelial cell attachment to the lumen of ECM-derived vascular conduits, potentially through recruitment of heparin-binding growth factors that ultimately improve the durability of endothelialization in vitro. Overall, our findings provide a simple yet effective method to increase deposition of functional heparin on the surface of ECM-based vascular grafts and thereby minimize thrombogenicity of decellularized tissue, overcoming a significant challenge in tissue engineering of bioartificial vessels and vascularized organs.

Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration.

Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we demonstrate the role of two specific populations of bone marrow (BM) stem/progenitor cells used in combination with a synthetic elastomeric scaffold that provides a unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34(+) hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34(+) grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.

Biodegradable elastomers and silicon nanomembranes/nanoribbons for stretchable, transient electronics, and biosensors.

Transient electronics represents an emerging class of technology that exploits materials and/or device constructs that are capable of physically disappearing or disintegrating in a controlled manner at programmed rates or times. Inorganic semiconductor nanomaterials such as silicon nanomembranes/nanoribbons provide attractive choices for active elements in transistors, diodes and other essential components of overall systems that dissolve completely by hydrolysis in biofluids or groundwater. We describe here materials, mechanics, and design layouts to achieve this type of technology in stretchable configurations with biodegradable elastomers for substrate/encapsulation layers. Experimental and theoretical results illuminate the mechanical properties under large strain deformation. Circuit characterization of complementary metal-oxide-semiconductor inverters and individual transistors under various levels of applied loads validates the design strategies. Examples of biosensors demonstrate possibilities for stretchable, transient devices in biomedical applications.

Periadventitial atRA citrate-based polyester membranes reduce neointimal hyperplasia and restenosis after carotid injury in rats.

Oral all-trans retinoic acid (atRA) has been shown to reduce the formation of neointimal hyperplasia; however, the dose required was 30 times the chemotherapeutic dose, which already has reported side effects. As neointimal formation is a localized process, new approaches to localized delivery are required. This study assessed whether atRA within a citrate-based polyester, poly(1,8 octanediolcitrate) (POC), perivascular membrane would prevent neointimal hyperplasia following arterial injury. atRA-POC membranes were prepared and characterized for atRA release via high-performance liquid chromatography with mass spectrometry detection. Rat adventitial fibroblasts (AF) and vascular smooth muscle cells (VSMC) were exposed to various concentrations of atRA; proliferation, apoptosis, and necrosis were assessed in vitro. The rat carotid artery balloon injury model was used to evaluate the impact of the atRA-POC membranes on neointimal formation, cell proliferation, apoptosis, macrophage infiltration, and vascular cell adhesion molecule 1 (VCAM-1) expression in vivo. atRA-POC membranes released 12 µg of atRA over 2 wk, with 92% of the release occurring in the first week. At 24 h, atRA (200 µmol/l) inhibited [(3)H]-thymidine incorporation into AF and VSMC by 78% and 72%, respectively (*P = 0.001), with negligible apoptosis or necrosis. Histomorphometry analysis showed that atRA-POC membranes inhibited neointimal formation after balloon injury, with a 56%, 57%, and 50% decrease in the intimal area, intima-to-media area ratio, and percent stenosis, respectively (P = 0.001). atRA-POC membranes had no appreciable effect on apoptosis or proliferation at 2 wk. Regarding biocompatibility, we found a 76% decrease in macrophage infiltration in the intima layer (P < 0.003) in animals treated with atRA-POC membranes, with a coinciding 53% reduction in VCAM-1 staining (P < 0.001). In conclusion, perivascular delivery of atRA inhibited neointimal formation and restenosis. These data suggest that atRA-POC membranes may be suitable as localized therapy to inhibit neointimal hyperplasia following open cardiovascular procedures.

A thermoresponsive biodegradable polymer with intrinsic antioxidant properties.

Oxidative stress in tissue can contribute to chronic inflammation that impairs wound healing and the efficacy of cell-based therapies and medical devices. We describe the synthesis and characterization of a biodegradable, thermoresponsive gel with intrinsic antioxidant properties suitable for the delivery of therapeutics. Citric acid, poly(ethylene glycol) (PEG), and poly-N-isopropylacrylamide (PNIPAAm) were copolymerized by sequential polycondensation and radical polymerization to produce poly(polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN). PPCN was chemically characterized, and the thermoresponsive behavior, antioxidant properties, morphology, potential for protein and cell delivery, and tissue compatibility in vivo were evaluated. The PPCN gel has a lower critical solution temperature (LCST) of 26 °C and exhibits intrinsic antioxidant properties based on its ability to scavenge free radicals, chelate metal ions, and inhibit lipid peroxidation. PPCN displays a hierarchical architecture of micropores and nanofibers, and contrary to typical thermoresponsive polymers, such as PNIPAAm, PPCN gel maintains its volume upon formation. PPCN efficiently entrapped and slowly released the chemokine SDF-1α and supported the viability and proliferation of vascular cells. Subcutaneous injections in rats showed that PPCN gels are resorbed over time and new connective tissue formation takes place without signs of significant inflammation. Ultimately, this intrinsically antioxidant, biodegradable, thermoresponsive gel could potentially be used as an injectable biomaterial for applications where oxidative stress in tissue is a concern.

A receptor-based bioadsorbent to target advanced glycation end products in chronic kidney disease.

The accumulation of advanced glycation end products (AGEs) has been reported to be a major contributor to chronic systemic inflammation. AGEs are not efficiently removed by hemodialysis or the kidney of a chronic kidney disease (CKD) patient. The goal of this study was to develop a receptor for AGEs (RAGE)-based bioadsorbent device that was capable of removing endogenous AGEs from human blood. The extracellular domain of RAGE was immobilized onto agarose beads to generate the bioadsorbent. The efficacy of AGE removal from saline, serum, and whole blood; biological effects of AGE reduction; and hemocompatibility and stability of the bioadsorbent were investigated. The bioadsorbent bound AGE-modified bovine serum albumin (AGE-BSA) with a binding capacity of 0.73 ± 0.07 mg AGE-BSA/mL bioadsorbent. The bioadsorbent significantly reduced the concentration of total AGEs in serum isolated from end-stage kidney disease patients by 57%. AGE removal resulted in a significant reduction of vascular cell adhesion molecule-1 expression in human endothelial cells and abolishment of osteoclast formation in osteoclast progenitor cells. A hollow fiber device loaded with bioadsorbent-reduced endogenous AGEs from recirculated blood to 36% of baseline levels with no significant changes in total protein or albumin concentration. The bioadsorbent maintained AGE-specific binding capacity after freeze-drying and storage for 1 year. This approach provides the foundation for further development of soluble RAGE-based extracorporeal therapies to selectively deplete serum AGEs from human blood and decrease inflammation in patients with diabetes and/or CKD.

Enabling Proregenerative Medical Devices via Citrate-Based Biomaterials: Transitioning from Inert to Regenerative Biomaterials.

Regenerative medicine aims to restore tissue and organ function without the use of prosthetics and permanent implants. However, achieving this goal has been elusive, and the field remains mostly an academic discipline with few products widely used in clinical practice. From a materials science perspective, barriers include the lack of proregenerative biomaterials, a complex regulatory process to demonstrate safety and efficacy, and user adoption challenges. Although biomaterials, particularly biodegradable polymers, can play a major role in regenerative medicine, their suboptimal mechanical and degradation properties often limit their use, and they do not support inherent biological processes that facilitate tissue regeneration. As of 2020, nine synthetic biodegradable polymers used in medical devices are cleared or approved for use in the United States of America. Despite the limitations in the design, production, and marketing of these devices, this small number of biodegradable polymers has dominated the resorbable medical device market for the past 50 years. This perspective will review the history and applications of biodegradable polymers used in medical devices, highlight the need and requirements for regenerative biomaterials, and discuss the path behind the recent successful introduction of citrate-based biomaterials for manufacturing innovative medical products aimed at improving the outcome of musculoskeletal surgeries.

Phase-changing citrate macromolecule combats oxidative pancreatic islet damage, enables islet engraftment and function in the omentum.

Clinical outcomes for total-pancreatectomy followed by intraportal islet autotransplantation (TP-IAT) to treat chronic pancreatitis (CP) are suboptimal due to pancreas inflammation, oxidative stress during islet isolation, and harsh engraftment conditions in the liver's vasculature. We describe a thermoresponsive, antioxidant macromolecule poly(polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) to protect islet redox status and function and to enable extrahepatic omentum islet engraftment. PPCN solution transitions from a liquid to a hydrogel at body temperature. Islets entrapped in PPCN and exposed to oxidative stress remain functional and support long-term euglycemia, in contrast to islets entrapped in a plasma-thrombin biologic scaffold. In the nonhuman primate (NHP) omentum, PPCN is well-tolerated and mostly resorbed without fibrosis at 3 months after implantation. In NHPs, autologous omentum islet transplantation using PPCN restores normoglycemia with minimal exogenous insulin requirements for >100 days. This preclinical study supports TP-IAT with PPCN in patients with CP and highlights antioxidant properties as a mechanism for islet function preservation.

Panthenol Citrate Biomaterials Accelerate Wound Healing and Restore Tissue Integrity.

Impaired wound healing is a common complication for diabetic patients and effective diabetic wound management remains a clinical challenge. Furthermore, a significant problem that contributes to patient morbidity is the suboptimal quality of healed skin, which often leads to reoccurring chronic skin wounds. Herein, a novel compound and biomaterial building block, panthenol citrate (PC), is developed. It has interesting fluorescence and absorbance properties, and it is shown that PC can be used in soluble form as a wash solution and as a hydrogel dressing to address impaired wound healing in diabetes. PC exhibits antioxidant, antibacterial, anti-inflammatory, and pro-angiogenic properties, and promotes keratinocyte and dermal fibroblast migration and proliferation. When applied in a splinted excisional wound diabetic rodent model, PC improves re-epithelialization, granulation tissue formation, and neovascularization. It also reduces inflammation and oxidative stress in the wound environment. Most importantly, it improves the regenerated tissue quality with enhanced mechanical strength and electrical properties. Therefore, PC could potentially improve wound care management for diabetic patients and play a beneficial role in other tissue regeneration applications.

3D-Printed Electroactive Hydrogel Architectures with Sub-100 µm Resolution Promote Myoblast Viability.

3D-printed hydrogel scaffolds functionalized with conductive polymers have demonstrated significant potential in regenerative applications for their structural tunability, physiochemical compatibility, and electroactivity. Controllably generating conductive hydrogels with fine features, however, has proven challenging. Here, micro-continuous liquid interface production (µCLIP) method is utilized to 3D print poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels. With a unique in-situ polymerization approach, a sulfonated monomer is first incorporated into the hydrogel matrix and subsequently polymerized into a conjugated polyelectrolyte, poly(4-(2,3-dihydro-thieno[3,4-b][1,4]dioxin-2-ylmethoxy)-butane-1 sulfonic acid sodium salt (PEDOT-S). Rod structures are fabricated at different crosslinking levels to investigate PEDOT-S incorporation and its effect on bulk hydrogel electronic and mechanical properties. After demonstrating that PEDOT-S does not significantly compromise the structures of the bulk material, pHEMA scaffolds are fabricated via µCLIP with features smaller than 100 µm. Scaffold characterization confirms PEDOT-S incorporation bolstered conductivity while lowering overall modulus. Finally, C2C12 myoblasts are seeded on PEDOT-pHEMA structures to verify cytocompatibility and the potential of this material in future regenerative applications. PEDOT-pHEMA scaffolds promote increased cell viability relative to their non-conductive counterparts and differentially influence cell organization. Taken together, this study presents a promising new approach for fabricating complex conductive hydrogel structures for regenerative applications.

Long-term in vivo response to citric acid-based nanocomposites for orthopaedic tissue engineering.

The disadvantages of current bone grafts have triggered the development of a variety of natural and synthetic bone substitutes. Previously, we have described the fabrication, characterization, and short-term tissue response of poly(1,8-octanediol-co-citrate) (POC) with 60 weight % hydroxyapatite nanocrystals (POC-HA) at 6 weeks. In order to better understand the clinical potential, longer term effects, and the biodegradation, biocompatibility, and bone regenerative properties of these novel nanocomposites, POC-HA, POC, and poly-L-lactide (PLL) were implanted in osteochondral defects in a rabbit model and assessed at 26 weeks. Explants were stained with Masson Goldner Trichrome and the fibrous capsule and tissue ingrowth measured. In addition, the bone-implant and bone-cartilage response of POC-HA, POC, and PLL were assessed through histomorphometry and histological scoring. Upon histological evaluation, both POC-HA and POC implants were biocompatible, but PLL implants were surrounded by a layer of leukocytes at 26 weeks. In addition, due to the degradation properties of POC-HA, tissue grew into the implant and had the highest area of tissue ingrowth although not statistically significant. Histomorphometric analyses supported a similar osteoid, osteoblast, and trabecular bone surface area among all implants although the fibrous capsule thickness was the largest for POC. Moreover, histological scoring demonstrated comparable scores among all three groups of the articular cartilage and subchondral bone. This study provides the long-term bone and cartilage response of novel, citric acid-based nanocomposites and their equivalence to FDA-approved biomaterials. Furthermore, we provide new insights and further discussion of these nanocomposites for orthopaedic applications.

Stretchable, dynamic covalent polymers for soft, long-lived bioresorbable electronic stimulators designed to facilitate neuromuscular regeneration.

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.

Polymer-integrated amnion scaffold significantly improves cleft palate repair.

Cleft palate is a common oral and craniomaxillofacial birth defect. As the ideal surgery time is shortly after birth, clinical treatments should result in minimal disruption of theskeleton to allow tissue growth in children. A tissue-engineered graft was created in this study for cleft palate repair by integrating poly(1,8-octamethylene-citrate) (POC) with a decellularized amnion membrane (DAM-POC) to incorporate the advantages of both the synthetic polymer and the native tissue. The success of POC incorporation was confirmed by laser-induced breakdown spectroscopy and fluorescence detection. The DAM-POC scaffold showed a certain level of structure collapse and lower stiffness but better resistance to enzyme digestion than the native amnion and DAM scaffold. The DAM-POC scaffold is cell compatible when seeded with mesenchymal stem cells, as evidenced by adequate cell viability and improved alkaline phosphatase (ALP) activity and calcium deposit. A large palate defect was first surgically created in a young rat model and then repaired with the DAM-POC scaffold. Eight weeks postsurgery, histological study and CT scans showed nearly complete healing of both soft and hard tissues. In conclusion, we developed a cell-free, resorbable graft by incorporating and integrating a synthetic polymer with a human DAM. When the DAM-POC scaffold was applied to repair a large palate defect in young rats, it showed adequate biocompatibility as evidenced by its effectiveness in guiding hard and soft tissue regeneration and minimum interference with natural growth and palate development of rats. STATEMENT OF SIGNIFICANCE: Proper restoration of severe cleft palate remains a major challenge because of insufficient autologous soft tissues to close the open wounds, thereby causing high tension at the surgical junction, secondary palatal fistulas, wound contraction, scar tissue formation, and facial growth disturbances. In this study, we have developed a tissue-engineered graft through incorporating and integrating a synthetic polymer with the human amnion membrane for cleft palate repair. The significance of this study lies in our ability to develop a cell-free, resorbable graft that can provide a less surgically invasive option to cover the open defect and support palate regeneration and tissue growth. This technique could potentially advance soft and hard tissue regeneration in children with birth craniomaxillofacial defects.

A thermoresponsive, citrate-based macromolecule for bone regenerative engineering.

There is a need in orthopaedic and craniomaxillofacial surgeries for materials that are easy to handle and apply to a surgical site, can fill and fully conform to the bone defect, and can promote the formation of new bone tissue. Thermoresponsive polymers that undergo liquid to gel transition at physiological temperature can potentially be used to meet these handling and shape-conforming requirements. However, there are no reports on their capacity to induce in vivo bone formation. The objective of this research was to investigate whether the functionalization of the thermoresponsive, antioxidant macromolecule poly(poly-ethyleneglycol citrate-co-N-isopropylacrylamide) (PPCN), with strontium, phosphate, and/or the cyclic RGD peptide would render it a hydrogel with osteoinductive properties. We show that all formulations of functionalized PPCN retain thermoresponsive properties and can induce osteodifferentiation of human mesenchymal stem cells without the need for exogenous osteogenic supplements. PPCN-Sr was the most osteoinductive formulation in vitro and produced robust localized mineralization and osteogenesis in subcutaneous and intramuscular tissue in a mouse model. Strontium was not detected in any of the major organs. Our results support the use of functionalized PPCN as a valuable tool for the recruitment, survival, and differentiation of cells critical to the development of new bone and the induction of bone formation in vivo. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1743-1752, 2018.

Inhibiting intimal hyperplasia in prosthetic vascular grafts via immobilized all-trans retinoic acid.

Peripheral arterial disease is a leading cause of morbidity and mortality. The most commonly utilized prosthetic material for peripheral bypass grafting is expanded polytetrafluoroethylene (ePTFE) yet it continues to exhibit poor performance from restenosis due to neointimal hyperplasia, especially in femoral distal bypass procedures. Recently, we demonstrated that periadventitial delivery of all-trans retinoic acid (atRA) immobilized throughout porous poly(1,8 octamethylene citrate) (POC) membranes inhibited neointimal formation in a rat arterial injury model. Thus, the objective of this study was to investigate whether atRA immobilized throughout the lumen of ePTFE vascular grafts would inhibit intimal formation following arterial bypass grafting. Utilizing standard ePTFE, two types of atRA-containing ePTFE vascular grafts were fabricated and evaluated: grafts whereby all-trans retinoic acid was directly immobilized on ePTFE (atRA-ePTFE) and grafts where all-trans retinoic acid was immobilized onto ePTFE grafts coated with POC (atRA-POC-ePTFE). All grafts were characterized by SEM, HPLC, and FTIR and physical characteristics were evaluated in vitro. Modification of these grafts, did not significantly alter their physical characteristics or biocompatibility, and resulted in inhibition of intimal formation in a rat aortic bypass model, with atRA-POC-ePTFE inhibiting intimal formation at both the proximal and distal graft sections. In addition, treatment with atRA-POC-ePTFE resulted in increased graft endothelialization and decreased inflammation when compared to the other treatment groups. This work further confirms the biocompatibility and efficacy of locally delivered atRA to inhibit intimal formation in a bypass setting. Thus, atRA-POC-ePTFE grafts have the potential to improve patency rates in small diameter bypass grafts and warrant further investigation.

Spectroscopic translation of cell-material interactions.

The characterization of cellular interactions with a biomaterial surface is important to the development of novel biomaterials. Traditional methods used to characterize processes such as cellular adhesion and differentiation on biomaterials can be time consuming, and destructive, and are not amenable to quantitative assessment in situ. As the development of novel biomaterials shifts towards small-scale, combinatorial, and high throughput approaches, new techniques will be required to rapidly screen and characterize cell/biomaterial interactions. Towards this goal, we assessed the feasibility of using 4-dimensional elastic light-scattering fingerprinting (4D-ELF) to describe the differentiation of human aortic smooth muscle cells (HASMCs), as well as the adhesion, and apoptotic processes of human aortic endothelial cells (HAECs), in a quantitative and non-perturbing manner. HASMC and HAEC were cultured under conditions to induce cell differentiation, attachment, and apoptosis which were evaluated via immunohistochemistry, microscopy, biochemistry, and 4D-ELF. The results show that 4D-ELF detected changes in the size distributions of subcellular organelles and structures that were associated with these specific cellular processes. 4D-ELF is a novel way to assess cell phenotype, strength of adhesion, and the onset of apoptosis on a biomaterial surface and could potentially be used as a rapid and quantitative screening tool to provide a more in-depth understanding of cell/biomaterial interactions.

A biodegradable vascularizing membrane: a feasibility study.

Regenerative medicine and in vivo biosensor applications require the formation of mature vascular networks for long-term success. This study investigated whether biodegradable porous membranes could induce the formation of a vascularized fibrous capsule and, if so, the effect of degradation kinetics on neovascularization. Poly(l-lactic acid) (PLLA) and poly(dl-lactic-co-glycolic) acid (PLGA) membranes were created by a solvent casting/salt leaching method. Specifically, PLLA, PLGA 75:25 and PLGA 50:50 polymers were used to vary degradation kinetics. The membranes were designed to have an average 60mum pore diameter, as this pore size has been shown to be optimal for inducing blood vessel formation around nondegradable polymer materials. Membrane samples were imaged by scanning electron microscopy at several time points during in vitro degradation to assess any changes in pore structure. The in vivo performance of the membranes was assessed in Sprague-Dawley rats by measuring vascularization within the fibrous capsule that forms adjacent to implants. The vascular density within 100microm of the membranes was compared with that seen in normal tissue, and to that surrounding the commercially available vascularizing membrane TheraCyte. The hemoglobin content of tissue containing the membranes was measured by four-dimensional elastic light scattering as a novel method to assess tissue perfusion. Results from this study show that slow-degrading membranes induce greater amounts of neovascularization and a thinner fibrous capsule relative to fast degrading membranes. These results may be due both to an initially increased number of macrophages surrounding the slower degrading membranes and to the maintenance of their initial pore structure.

A tough biodegradable elastomer.

Biodegradable polymers have significant potential in biotechnology and bioengineering. However, for some applications, they are limited by their inferior mechanical properties and unsatisfactory compatibility with cells and tissues. A strong, biodegradable, and biocompatible elastomer could be useful for fields such as tissue engineering, drug delivery, and in vivo sensing. We designed, synthesized, and characterized a tough biodegradable elastomer from biocompatible monomers. This elastomer forms a covalently crosslinked, three-dimensional network of random coils with hydroxyl groups attached to its backbone. Both crosslinking and the hydrogen-bonding interactions between the hydroxyl groups likely contribute to the unique properties of the elastomer. In vitro and in vivo studies show that the polymer has good biocompatibility. Polymer implants under animal skin are absorbed completely within 60 days with restoration of the implantation sites to their normal architecture.

A biodegradable tri-component graft for anterior cruciate ligament reconstruction.

Bone-patellar tendon-bone (BPTB) autografts are the gold standard for anterior cruciate ligament (ACL) reconstruction because the bony ends allow for superior healing and anchoring through bone-to-bone regeneration. However, the disadvantages of BPTB grafts include donor site morbidity and patellar rupture. In order to incorporate bone-to-bone healing without the risks associated with harvesting autogenous tissue, a biodegradable and synthetic tri-component graft was fabricated, consisting of porous poly(1,8-octanediol-co-citric acid)-hydroxyapatite nanocomposites (POC-HA) and poly(l-lactide) (PLL) braids. All regions of the tri-component graft were porous and the tensile properties were in the range of the native ACL. When these novel grafts were used to reconstruct the ACL of rabbits, all animals after 6 weeks were weight-bearing and showed good functionality. Histological assessment confirmed tissue infiltration throughout the entire scaffold and tissue ingrowth and interlocking within the bone tunnels, which is favourable for graft fixation. In conclusion, this pilot study suggests that a tri-component, biodegradable graft is a promising strategy to regenerate tissue types necessary for ACL tissue engineering, and provides a basis for developing an off-the-shelf graft for ACL repair. Copyright © 2014 John Wiley & Sons, Ltd.