Abstract: The present invention provides microparticles that induce the migration of multipotent stem cells to the anatomical site of the microparticles. Various release profiles are demonstrated that depend upon the relative concentration of alginate in the chemokine-loaded microparticle. Local administration and/or intraarticular injection of the microparticles are useful in conditions such as osteoarthritis. Targeted systemic delivery of the alginate chemokine microparticles to distant anatomical sites subjected to autoimmune disease symptomology can be performed by encapsulation within liposomes having targeting ligands. Consequently, upon the creation of the appropriate chemokine gradient, multipotent stem cells will migrate to the distant anatomical site where the liposomes are attached.

Abstract: Methods for inhibiting tissue ossification or calcification in a subject, comprising administering a therapeutically effective amount of BMP I inhibitor-loaded microparticles to a subject in need thereof, wherein the administration provides local and sustained release of the BMP I inhibitor thereby inhibiting tissue ossification or calcification.

Abstract: A Fe(II)- and Ca+2-chelated alginate/gelatin conjugate.

Abstract: A method for sustained delivery of an agent to an ocular organ in a subject, comprising topically delivering to the ocular surface a liquid thermoresponsive hydrogel comprising agent-loaded polymer microparticles, wherein the agent is an antibody, a fusion protein, a chemokine, an interleukin, a growth factor, albumin, immunoglobulin, an interferon, a peptide, stem cell-conditioned media, plasma or serum.

Abstract: The present invention provides microparticles that deliver in vivo predictable release profiles of at least one chemokine to create a biomimetic chemokine concentration gradient that induces the migration of multipotent stem cells to the anatomical site of the microparticles. Various release profiles are demonstrated that depend upon the relative concentration of alginate in the chemokine-loaded microparticle. Local administration and/or intraarticular injection of the microparticles are useful in conditions such as osteoarthritis. Targeted systemic delivery of the alginate chemokine microparticles to distant anatomical sites subjected to autoimmune disease symptomology can be performed by encapsulation within liposomes having targeting ligands. Consequently, upon the creation of the appropriate chemokine gradient, multipotent stem cells will migrate to the distant anatomical site where the liposomes are attached.

Abstract: Methods for inhibiting tissue ossification or calcification in a subject, comprising administering a therapeutically effective amount of BMP I inhibitor-loaded microparticles to a subject in need thereof, wherein the administration provides local and sustained release of the BMP I inhibitor thereby inhibiting tissue ossification or calcification.

Abstract: The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (Treg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound Treg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.

Abstract: A method for treating an ocular disorder in a subject comprising administering a therapeutic agent-loaded carrier to an ocular site of the subject in need thereof, wherein the therapeutic agent loaded-carrier provides controlled delivery of the therapeutic agent under conditions suitable for recruiting regulatory T cells to an ocular region of interest or inducing regulatory T cells in an ocular region of interest.

Abstract: A method for making a modified release composition, comprising: selecting a desired active agent and polymer matrix for formulating into a modified release composition; assessing degradation effect on release of the active agent from the composition including plotting polymer molecular weight (Mwr) at onset of active agent release vs. active agent molecular weight (MwA); predicting performance of multiple potential formulations for the composition based on the degradation assessment and average polymer matrix initial molecular weight (Mwo) to define a library of building blocks; determining the optimal ratio of the building blocks to satisfy a specified release profile; and making a modified release composition based on the optimal ratio determination.

Abstract: The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (Treg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound Treg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.

Abstract: Methods for inhibiting tissue ossification or calcification in a subject, comprising administering a therapeutically effective amount of BMP I inhibitor-loaded microparticles to a subject in need thereof, wherein the administration provides local and sustained release of the BMP I inhibitor thereby inhibiting tissue ossification or calcification.

Abstract: A method for sustained delivery of an agent to an ocular organ in a subject, comprising topically delivering to the ocular surface a liquid thermoresponsive hydrogel comprising agent-loaded polymer microparticles, wherein the agent is sustainably released for a period of at least five days.

Abstract: A method for making microparticles having an exterior surface that includes preparing a self-assembled arrangement of microparticles; contacting the self-assembled microparticles with a patch-forming agent resulting in a microparticle/patch-forming agent assembly having proximal regions between adjacent microparticles and/or proximal regions between a microparticle and another substrate, wherein the patch-forming agent is present in the proximal region; and condensing the patch-forming agent such that a pattern of a plurality of discrete patches of patch-forming agent are formed on the exterior surfaces of the microparticles at the proximal regions. A synthetic microsphere having an exterior spherical surface, wherein the exterior spherical surface comprises a first material and a plurality of discrete, uniformly-dimensioned, patches of a second bioactive material arranged in an orderly array over more than one hemisphere of the microsphere.

Abstract: The present invention provides microparticles that deliver in vivo predictable release profiles of at least one chemokine to create a biomimetic chemokine concentration gradient that induces the migration of multipotent stem cells to the anatomical site of the microparticles. Various release profiles are demonstrated that depend upon the relative concentration of alginate in the chemokine-loaded microparticle. Local administration and/or intraarticular injection of the microparticles are useful in conditions such as osteoarthritis. Targeted systemic delivery of the alginate chemokine microparticles to distant anatomical sites subjected to autoimmune disease symptomology can be performed by encapsulation within liposomes having targeting ligands. Consequently, upon the creation of the appropriate chemokine gradient, multipotent stem cells will migrate to the distant anatomical site where the liposomes are attached.

Abstract: The absence of regulatory T cells (Treg) may underlie disorders including but not limited to autoimmunity, dermatitis, periodontitis and even transplant rejection. Enhancing local numbers of Treg through in situ Treg expansion or induction is contemplated herein as a treatment option for these disorders. Current methods for in vivo Treg expansion are not Treg specific and are associated with many adverse side-effects. The data presented herein provides in vitro testing of a Treg-inducing microparticle providing a predictable controlled release for combinations of cytokines and drugs (e.g., IL-2, TGF-?, and/or rapamycin) resulting in targeted Treg migration. These controlled release microparticles are also capable of inducing FoxP3+ Treg in human cells in vitro suggesting that these compositions be developed into an in vivo Treg induction and expansion therapy.

Abstract: The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (Treg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound Treg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.

Abstract: The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (Treg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound Treg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.

Abstract: Controlled release of VIP from PLGA microparticles was accomplished and varied through use of different polymer molecular sizes, addition of solutes to the inner aqueous phase, and use of our computer model. Released VIP from microparticles appeared to be bioactive and caused DCs to produce more CCL22 than DCs treated with blank particles at 7 and 24 hours. Additionally, DCs treated with VIP microparticle releasates recruited higher percentages of FoxP3+ T-cells in in vitro chemotaxis studies. Testing in a mouse model in vivo indicated that VIP microparticles have significant therapeutic potential to treat periodontal disease by reducing the bone loss in infected mice relative to the blank group.

Abstract: A method for making microparticles having an exterior surface that includes preparing a self-assembled arrangement of microparticles; contacting the self-assembled microparticles with a patch-forming agent resulting in a microparticle/patch-forming agent assembly having proximal regions between adjacent microparticles and/or proximal regions between a microparticle and another substrate, wherein the patch-forming agent is present in the proximal region; and condensing the patch-forming agent such that a pattern of a plurality of discrete patches of patch-forming agent are formed on the exterior surfaces of the microparticles at the proximal regions. A synthetic microsphere having an exterior spherical surface, wherein the exterior spherical surface comprises a first material and a plurality of discrete, uniformly-dimensioned, patches of a second bioactive material arranged in an orderly array over more than one hemisphere of the microsphere.

Abstract: A method for making a modified release composition, comprising: selecting a desired active agent and polymer matrix for formulating into a modified release composition; assessing degradation effect on release of the active agent from the composition including plotting polymer molecular weight (Mwr) at onset of active agent release vs. active agent molecular weight (MwA); predicting performance of multiple potential formulations for the composition based on the degradation assessment and average polymer matrix initial molecular weight (Mwo) to define a library of building blocks; determining the optimal ratio of the building blocks to satisfy a specified release profile; and making a modified release composition based on the optimal ratio determination.