Methods for making a biodegradable collagen matrix having increased osteoinductivity and a biodegradable collagen matrix prepared by these methods are provided. In various embodiments, the methods include providing an acidic collagen slurry and mixing it with at least one water soluble and/or hydrophilic bioactive agent under conditions sufficient to cause the collagen slurry to self-assemble into macroscopic collagen fibers and cause the at least one bioactive agent to form a collagen matrix containing the bioactive agent. Conditions sufficient to cause the collagen slurry to self-assembly include raising the pH of the slurry to from about 5 to about a pH of 9 and/or adding bone powder, calcium phosphate, hydroxyapatite, DBM or a mixture thereof to the acidic collagen slurry in order to raise the pH from about 5 to about 9.
